Journal

Acta Obstetricia et Gynecologica Scandinavica

Papers (132)

Exploring endometrial cancer in premenopausal women—A nationwide PremEnCa cohort study

Abstract Introduction An increased incidence of endometrial cancer has been noted, especially in premenopausal women in countries with rapid socioeconomic transition. In one of the largest patient cohorts of women ≤50 years, with manually validated register data, we aim to examine the pattern of disease of endometrial cancer and to evaluate the prognosis according to tumor and patient characteristics, focusing on body mass index. Material and Methods This is a nationwide population‐based study on women ≤50 years with endometrial cancer, 2010–2021, using data from Swedish registries complemented by the reviewing of medical records. Overall survival and disease‐free survival were calculated by the Kaplan–Meier method and the log‐rank test. Multivariable regression analyses were performed. Results Of the total endometrial cancer cohort, 797 (5%) patients were ≤50 years of age (the PremEnCa cohort) with 0.9% under 40 years of age. Women ≤50 years of age had a higher prevalence of stage IA and endometrioid histology than older women. Among women ≤50 years of age, 46% met the criteria for obesity. No associations between socioeconomic factors and stage at diagnosis were found. Notably, women with lower Body Mass Index <20, had a higher proportion of non‐endometrioid histology and higher stage of disease at the time of diagnosis. Median follow‐up time was 4.2 (IOR 1.9–5.4) years. The recurrence rate was 6.1% in the PremEnCa cohort during the follow‐up period, and the 5‐year overall survival was 94.6% (95% CI: 92.6–96.0) for endometrioid and 68.5% (95% CI: 51.1–80.8) for non‐endometrioid endometrial cancer. Only 36 of the 74 deaths were caused by endometrial cancer. In adjusted analyses for disease‐free survival, non‐endometrioid histology and International Federation of Gynecology and Obstetrics (FIGO) stage were associated with worse prognosis. Conclusions Endometrial cancer in premenopausal women is very rare and is associated with an excellent prognosis. Histology and FIGO stage were the strongest prognostic factors. Half of the deaths were due to other causes, which emphasizes the importance of focusing on general health aspects in this young endometrial cancer population.

Implementation of extensive cytoreductive surgery protocol in advanced epithelial ovarian cancer: Real‐world data on surgical treatment distribution and survival of the whole patient cohort; a single center experience

AbstractIntroductionThe aim was to assess the effect of the implementation of maximal surgical cytoreduction on the treatment decisions and overall survival of the entire patient cohort with advanced epithelial ovarian cancer.Material and MethodsWe collected retrospectively all newly diagnosed patients with FIGO stage IIIB–IVB epithelial ovarian cancer between 2013 and 2019 in Tampere University Hospital, Finland. Altogether, 333 patients were divided into two groups based on the date of diagnosis: Group 1 (n = 162) diagnosed before March 2016 and Group 2 (n = 171) after 1st of March 2016, when a systematic change in surgical approach toward maximal surgical cytoreduction was implemented in our institution.ResultsNo statistically significant differences were found in the proportions of patients having surgery or treated non‐surgically between the two time periods: 76.5% of patients in Group 1 and 71.9% in Group 2 underwent surgical treatment, while the others were treated with chemotherapy only or referred directly to palliative care (p = 0.38). In addition, there was no statistically significant difference in overall survival in patients who received any treatment (surgery and chemotherapy or chemotherapy only) between groups: the median overall survival was 32.8 months (95% CI 25.1–40.5) in Group 1 and 37.3 months (31.5–43.1) in Group 2, p = 0.214.ConclusionsThe change in surgical approach toward maximal surgical cytoreduction in advanced epithelial ovarian cancer did not significantly change the magnitude of patients who received only chemotherapy or underwent surgical treatment in our center. While the shift in surgical paradigm may provide survival benefits for carefully selected surgically treated patients, it did not result in a statistically significant improvement in overall survival for the entire patient cohort.

Performance of radiomics analysis in ultrasound imaging for differentiating benign from malignant adnexal masses: A systematic review and meta‐analysis

AbstractIntroductionWe present the state of the art of ultrasound‐based machine learning (ML) radiomics models in the context of ovarian masses and analyze their accuracy in differentiating between benign and malignant adnexal masses.Material and MethodsWeb of Science, PubMed, and Scopus databases were searched. All studies were imported into RAYYAN QCRI software. All studies that developed and internally or externally validated ML models using only radiomics features extracted from ultrasound images were included. The overall quality of the included studies was assessed using the QUADAS‐AI tool. Summary sensitivity and specificity analyses with corresponding 95% confidence intervals (CIs) were reported.Results12 studies developed ML models including only radiomics features extracted from ultrasound images, and six of them were included in the meta‐analysis. The overall sensitivity and specificity for differentiating benign from malignant adnexal masses were 0.80 (95% CI 0.74–0.87) and 0.86 (95% CI 0.80–0.90), respectively, in the validation set. All studies demonstrated a high risk of bias in subject selection (e.g., lack of details on image sources or scanner models; absence of image preprocessing), and the majority also showed a high risk in the index test (e.g., models were not validated on external datasets) domain. In contrast, the risk of bias was generally low for the reference standard (i.e., most studies used a reference that accurately identified the target condition) and the testing workflow (i.e., the time interval between the index test and reference standard was appropriate) domains.ConclusionsThe good performance of ultrasound‐based radiomics models in the validation set supports that radiomics is worth exploring to improve the diagnosis of adnexal masses. So far, the studies have a high risk of bias due to the small sample size, single‐setting design, and no external validation included.

The complexity and challenges of fertility preservation in women with cervix cancer—A prospective cohort study reporting on reproductive outcome and overall survival

AbstractIntroductionOur objective was to assess the feasibility of fertility preservation (FP) in women referred for cervix cancer, the long‐term reproductive outcome, and overall survival.Material and MethodsProspective cohort study of patients referred for FP counseling between 1999 and 2021 to the FP program of Karolinska University Hospital, Stockholm, Sweden. Baseline data included age, parity, disease stage, treatment characteristics, and FP methods applied. Data on reproductive outcomes and overall survival (by October 19, 2023) were retrieved from clinical registries and a population‐based register. Trial registration number: ClinicalTrials.gov NTC04602962.ResultsIn total, 91 women were referred, 67% with stage I cancers and 25%, 7%, and 1% with stages II, III, and IV, respectively. Cancers were diagnosed during pregnancy or postpartum in six cases. Cancer treatments included fertility‐sparing surgery in 14%, hysterectomy in 30%, and radiochemotherapy in 79% of cases. The treatment modality did not rule out the possibility to undergo FP, and following counseling, 68 patients elected to undergo FP by cryopreservation of embryos or oocytes (N = 11), ovarian tissue (N = 54), or both (N = 3). After a mean follow‐up of 8.1 years, 25 women (37%) returned to the center, five women achieved conception either spontaneously or through assisted reproduction, and 11 women became mothers through adoption or surrogacy. In the group of women receiving radical surgery or chemo/radiotherapy, no live births using cryopreserved specimens have yet been achieved. During follow‐up, 7 women (10%) in the FP group and 5 women (24%) in the group without FP had died of their disease. Cancer recurrence was documented in 19 patients.ConclusionsOur findings underscore the complexity and challenges associated with FP in the context of cervix cancer. Results of this study demonstrate that many women diagnosed with cervix cancer at reproductive age desire to achieve parenthood. While fertility‐sparing surgery can allow pregnancy, those who undergo a hysterectomy are limited to adoption, surrogacy, or the emerging possibility of uterus transplantation.

Health‐related quality of life in adult‐type ovarian granulosa cell tumor survivors

AbstractIntroductionAdult‐type granulosa cell tumor (AGCT) is a rare, slow‐growing ovarian neoplasm with a tendency for late relapses. Surgery is the cornerstone of the treatment, and chemotherapy and hormonal treatment are administered in advanced and recurrent disease. The objective of our study was to assess health‐related quality of life (HRQoL) in AGCT survivors.Material and Methods15D and European Organization for Research and Treatment of Cancer (EORTC‐QLQ‐C30) questionnaires were collected from our prospective AGCT patient cohort, consisting of 171 AGCT survivors. The age‐standardized general female population was used as a reference for 15D comparison. Clinical and sociodemographic variables and EORTC‐QLQ‐C30 symptom and function scales were used as independent variables in regression analysis explaining the variance in the 15D score.ResultsEighty‐six women (50.3%), with a mean age of 68 years, returned the questionnaires. The HRQoL of AGCT survivors was similar to the general female population. The mean 15D score in our patient group was 0.891 (reference population score 0.899, p = 0.454). The scores were slightly lower on the 15D dimensions of excretion and sexual activity, whereas mental function scores were higher compared with the reference population. A history of tumor recurrence, an increasing number of other chronic illnesses, and financial difficulties each diminished HRQoL in our patient cohort. Regressing the EORTC variables on 15D produced a high explanatory power and accurate predictions of 15D scores.ConclusionsHRQoL of AGCT survivors was equal to that of the controls. Mapping EORTC‐QLQ‐C30 to 15D validly predicted 15D scores in AGCT survivors, confirming the usefulness of generic 15D for estimating quality‐adjusted life years in cancer patient trials.

Evaluation of a patient decision aid for opportunistic salpingectomy and salpingectomy as sterilization method to prevent ovarian cancer

AbstractIntroductionA patient decision aid on opportunistic salpingectomy and salpingectomy as a sterilization method has been developed to provide uniform counseling and reduce practice variation. The aim of this study was to evaluate the use of the patient decision aid in daily clinical practice to ensure its effectiveness and usability, as well as its influence on the decision‐making process and the decision of opportunistic salpingectomy.Material and MethodsAs part of the STOPOVCA‐implementation study, we conducted a multicenter observational study in 16 hospitals between July 2020 and February 2024. Patients who were eligible for opportunistic salpingectomy were invited to use the decision aid while they considered whether or not to undergo opportunistic salpingectomy. Digital questionnaires were used to evaluate the decision aid, the decision process, and patients' decisions 6–8 weeks post‐surgery.Results425 out of 542 patients participated in the questionnaire. A majority of these 425 patients received (N = 357; 84%) and used the decision aid (N = 347; 82%). Two thirds (N = 234; 67%) of those who used the decision aid stated that it increased their knowledge of opportunistic salpingectomy. Patients considered the decision aid a usable aid, allocating a score of 8.1 out of 10 and would recommend it to other patients facing the decision regarding opportunistic salpingectomy. Patients considered the extent to which they were involved in the decision‐making process as high, and the decisional conflict low. The majority of patients who used the decision aid opted for opportunistic salpingectomy (N = 326; 95%). Main reasons for choosing opportunistic salpingectomy were the risk‐reducing effect of ovarian cancer (N = 311; 90%) and the lack of functionality of the fallopian tubes after childbearing (N = 320; 92%).ConclusionsThe patient decision aid was used by a majority of patients who received it. The decision aid was regarded by patients as user‐friendly, and it was recommended to be used in the decision‐making process for opportunistic salpingectomy. Patients stated that the decision aid provides reliable information and increases patients' knowledge of opportunistic salpingectomy.

Hyperthermic intraperitoneal chemotherapy after upfront cytoreductive surgery for stage III epithelial ovarian cancer: Follow‐up of long‐term survival

AbstractIntroductionThe survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) has been well defined at the time of interval cytoreductive surgery, but the role of HIPEC remains uncertain for patients with newly diagnosed advanced ovarian cancer in the upfront setting. The present study aimed to report the updated long‐term survival outcomes after 5 years of follow‐up from our previous multicenter retrospective cohort study to compare primary cytoreductive surgery (PCS) plus HIPEC with PCS alone among women with stage III epithelial ovarian cancer.Material and MethodsThis study was conducted at five high‐volume gynecological medical centers in China from January 2010 to May 2017. Eligible patients with complete data were treated with either PCS combined with HIPEC or PCS alone. The 5‐year overall survival (OS) rate was updated to compare PCS plus HIPEC with PCS alone. The inverse probability of treatment weighting (IPTW) method based on a propensity score model for each patient was used to control the confounding factors and evaluate the effect of HIPEC.ResultsData from 789 patients, a total of 584 eligible stage III epithelial ovarian cancer patients were ultimately included in the analysis (PCS‐plus‐HIPEC group, n = 425; PCS‐alone group, n = 159). After IPTW adjustment, the median OS was 44.5 (95% CI, 40.1–49.1) months in the PCS‐plus‐HIPEC group and 32.4 (95% CI, 28.8–40.3) months in the PCS‐alone group (weighted hazard ratio, 0.74; 95% CI, 0.59–0.93; p = 0.006). At 5 years, the OS rates were 37.9% (95% CI, 33.0%–42.8%) in the PCS‐plus‐HIPEC group and 26.4% (95% CI, 18.9%–34.6%) in the PCS‐alone group (p = 0.007). After stratification into optimal and suboptimal cytoreduction subgroups, patients in the PCS‐plus‐HIPEC group maintained a greater association with improved OS than those in the PCS‐alone group. Among the women who underwent optimal cytoreduction in the PCS‐plus‐HIPEC group and PCS‐alone group, the median OS was 49.9 (95% CI, 45.2–58.4) months and 37.8 (95% CI, 30.5–53.0) months (p = 0.042) while the 5‐year OS rate was 43.7% (95% CI, 37.7%–49.6%) and 33.2% (95% CI, 23.3%–43.5%), respectively (p = 0.040). Meanwhile, for those treated with suboptimal cytoreduction subgroup in the PCS‐plus‐HIPEC and PCS‐alone groups, the median OS was 28.4 (95% CI, 22.2–39.9) months and 20.6 (95% CI, 10.6–32.4) months (p = 0.099) while the 5‐year OS rate was 22.4% (95% CI, 15.1%–30.5%) and 12.2% (95% CI, 4.4%–24.2%), respectively (p = 0.060). The median follow‐up period was 87.2 (95% CI, 85.1–92.7) months.ConclusionsThe updated results indicate that the addition of HIPEC is associated with improved long‐term survival outcomes beyond 5 years for patients with stage III epithelial ovarian cancer in the upfront setting.

COVID‐19 pandemic impact on gynecologic cancer treatment pathways in a Finnish tertiary center

AbstractIntroductionCOVID‐19 and new guidelines during the pandemic affected the gynecologic cancer treatment pathways, resulting in recorded delays and modifications in the treatment protocols. The aim of this study was to determine the impact of the COVID‐19 pandemic in one of the major gynecologic cancer care centers in Finland, Tampere University Hospital.Material and MethodsOur retrospective register study included 909 patients that were new gynecologic cancer cases (uterine, cervical, vulvar, vaginal, or ovarian) referred to the Tampere University Hospital Gynecologic Oncology Outpatient Clinic between March 17th, 2018, and March 15th, 2022. The patients were divided into two separate groups depending on their time of referral: time before COVID (March 17th, 2018, to March 15th, 2020), and during COVID (March 16th, 2020, to March 15th, 2022). These groups were compared in terms of patient characteristics, different cancer types and stages, symptoms, and treatment methods.ResultsDuring the COVID‐19 pandemic, patients generally suffered from cancer symptoms longer (p < 0.003) and were more likely to be overweight (p = 0.035). The improved multidisciplinary team meeting gave the patients a faster route to their first intervention during COVID (p < 0.05). An insignificant shift toward nonsurgical first interventions and non‐curative intent was seen during COVID, but the multidisciplinary team treatment plans were mostly implemented accordingly on both eras. No decrease was seen in the number of new gynecologic cancer cases, and the one‐year overall survival remained the same in both groups.ConclusionsOverall, the COVID‐19 pandemic did not significantly alter treatment pathways in gynecologic cancer care at Tampere University Hospital. The number of new patients and given treatments remained relatively stable. During COVID, access from referral to cancer treatment was significantly accelerated, which is likely confounded by changes to the multidisciplinary team protocol made in early 2021.

Do we more often opt for conservative management of ovarian tumors after changing the Dutch national guideline on enlarged ovaries? A nationwide cohort study

AbstractIntroductionIncreasing evidence shows that conservative management of ovarian tumors classified as benign, based on ultrasound assessment, is safe. Therefore, conservative management has been adopted as the preferred strategy for certain ovarian tumors assessed as benign in the Dutch national guideline on enlarged ovaries in 2013. The aim of this study was to examine whether implementation of this guideline has led to changes in the number of women/100 000 women undergoing surgery for an ovarian tumor in the Netherlands.Material and MethodsHistopathology reports were requested for all examinations of ovarian and fallopian tube specimens (including cyst enucleations) registered in Palga, the Dutch nationwide pathology databank, from 2011 (before guideline adaptation) and 2019 (after guideline adaptation). Reports on prophylactically removed adnexa, removal for other primary tumors (eg endometrial carcinoma), and for patients under 18 years of age, were excluded from the analysis. Interobserver agreement for the inclusion and classification of reports was assessed using Cohen's Kappa analysis.ResultsA total of 34 932 reports were retrieved, 13 917 of which were included in the analysis. In 2011 and 2019, respectively, 96.3/100 000 vs 68.8/100 000 women aged ≥18 underwent surgery for benign ovarian tumors, and 19.6/100 000 vs 18.3/100 000 for borderline and malignant tumors combined. The number of women/100 000 who had surgery for a benign ovarian tumor per 100 000 women declined by 28.5% (p < 0.001) between 2011 and 2019. The largest difference between 2011 and 2019 was observed in the number of women per 100 000 women who underwent surgery for a serous cystadenoma (−40.7%; 20.8/100 000 vs. 12.3/100 000), followed by endometrioma (−33.2%; 14.7/100 000 vs. 9.8/100 000), simple epithelial cyst (−57.3%; 8.4/100 000 vs. 3.6/100 000), and corpus luteum cyst (−57.0%; 4.0/100 000 vs. 1.7/100 000). Cohen's Kappa for the interobserver agreement was 0.96.ConclusionsThe number of women/100 000 undergoing surgery for a benign ovarian tumor has substantially decreased in the Netherlands when comparing data before and after implementation of the national guideline in 2013, while the number of women/100 000 undergoing surgery for a malignant or borderline tumor remained the same. These findings suggest successful implementation of the updated guideline, and a measurable effect on increased adoption of conservative management for benign‐looking ovarian tumors.

The educational game SonoQz improves diagnostic performance in ultrasound assessment of ovarian tumors

AbstractIntroductionOur objective was to determine whether the educational game SonoQz can improve diagnostic performance in ultrasound assessment of ovarian tumors.Material and MethodsThe SonoQz mobile application was developed as an educational tool for medical doctors to practice ultrasound assessment, based on still images of ovarian tumors. The game comprises images from 324 ovarian tumors, examined by an ultrasound expert prior to surgery. A training phase, where the participants assessed at least 200 cases in the SonoQz app, was preceded by a pretraining test, and followed by a posttraining test. Two equal tests (A and B), each consisting of 20 cases, were used as pre‐ and posttraining tests. Half the users took test A first, B second, and the remaining took the tests in the opposite order. Users were asked to classify the tumors (1) according to International Ovarian Tumor Analysis (IOTA) Simple Rules, (2) as benign or malignant, and (3) suggest a specific histological diagnosis. Logistic mixed models with fixed effects for pre‐ and posttraining tests, and crossed random effects for participants and cases, were used to determine any improvement in test scores, sensitivity, and specificity.ResultsFifty‐eight doctors from 19 medical centers participated. Comparing the pre‐ and posttraining test, the median of correctly classified cases, in Simple Rules assessment increased from 72% to 83%, p < 0.001; in classifying the lesion as benign or malignant tumors from 86% to 95%, p < 0.001; and in making a specific diagnosis from 43% to 63%, p < 0.001. When classifying tumors as benign or malignant, at an unchanged level of sensitivity (98% vs. 97%, p = 0.157), the specificity increased from 70% to 89%, p < 0.001.ConclusionsOur results indicate that the educational game SonoQz is an effective tool that may improve diagnostic performance in assessing ovarian tumors, specifically by reducing the number of false positives while maintaining high sensitivity.

Improvements and challenges in intraperitoneal laparoscopic para‐aortic lymphadenectomy: The novel “tent‐pitching” antegrade approach and vascular anatomical variations in the para‐aortic region

AbstractIntroductionThis study introduces and compares a new intraperitoneal laparoscopic para‐aortic lymphadenectomy method to reach the level of the renal vein, the “tent‐pitching” antegrade approach with the retrograde approach in gynecological malignancy surgeries in terms of success rate, complication incidence, and the number of lymph nodes removed. It focuses on the feasibility, safety, and effectiveness. Meanwhile, this article reports on the vascular anatomical variations discovered in the para‐aortic region to enhance surgical safety.Material and MethodsThis was a retrospective cohort study including patients undergone laparoscopic para‐aortic lymphadenectomy at a single center from January 2020 to December 2023 for high‐risk endometrial and early‐stage ovarian cancer. Patient charts were reviewed for mode of operation, perioperative complications, operative details, and histopathology. The patients were divided into anterograde group and retrograde group according to the operation mode. The two groups were further compared based on the success rate of lymph node clearance at the renal vein level, perioperative complications, and the number of removed lymph nodes. Quantitative data were analyzed using the t‐test, non‐normally distributed data using the rank‐sum test, and categorical data using Fisher's exact test and the chi‐square test, with statistical significance defined as P < 0.05.ResultsAmong 173 patients, the antegrade group showed higher surgery success (97.5% vs 68.82%), more lymph nodes removed (median 14 vs 7), and less median blood loss. The operation time was shorter in the antegrade group. Postoperative complications like lymphocele and venous thrombosis were lower in the antegrade group. Vascular abnormalities were found in 28.9% of patients, with accessory lumbar vein routing anomaly and accessory renal arteries being most common.ConclusionsThe antegrade approach is feasible, safe, and effective, improving surgical exposure, reducing difficulty without additional instruments or puncture sites, and minimizing organ damage risk. It is effective in achieving better access to the renal vein and removing more para‐aortic lymph nodes than the retrograde method. Recognizing and carefully managing the diverse vascular abnormalities in the para‐aortic area, including variations in renal arteries, veins, and the inferior vena cava, is essential to reduce intraoperative bleeding and the likelihood of converting to open surgery.

Previous cancers in women diagnosed with premature ovarian insufficiency: A nationwide population‐based case–control study

AbstractIntroductionTo investigate the occurrence of previous cancer diagnoses in women suffering from premature ovarian insufficiency (POI) and compare it with the general population, shedding light on the association between cancer, cancer treatments, and POI.Material and methodsWe conducted a nationwide case–control study based on registry data from various sources, including the Social Insurance Institution, Finnish Population Information System, and Finnish Cancer Registry spanning from 1953 to 2018. Our participants comprised all women in Finland who, between 1988 and 2017, received hormone replacement therapy reimbursement for ovarian insufficiency before the age of 40 years (n = 5221). Controls, matched in terms of age and municipality of residence, were selected from the Finnish Population Information System (n = 20 822). Our main exposure variable was a history of cancer diagnosis preceding the diagnosis of POI. We analyzed odds ratios (OR) to compare the prevalence of previous cancers in women with POI with that in controls, stratifying results based on cancer type, age at cancer diagnosis, and the time interval between cancer diagnosis and POI. We also assessed changes in OR for previous cancer diagnoses over the follow‐up period.ResultsOut of the women diagnosed with POI, 21.9% had previously been diagnosed with cancer, resulting in an elevated OR of 36.5 (95% confidence interval [CI] 30.9 to 43.3) compared with 0.8% of the controls. The risk of developing POI was most pronounced during the first 2 years following a cancer diagnosis, with an OR of 103 (95% CI 74.1 to 144). Importantly, this risk remained elevated even when the time interval between cancer and POI exceeded 10 years, with an OR of 5.40 (95% CI 3.54 to 8.23).ConclusionsThis study reveals that 21.9% of women with POI have a history of cancer, making the prevalence of cancer among these women 27.5 times higher than age‐matched controls in the Finnish population. The risk of developing POI is most substantial in the first 2 years following a cancer diagnosis. These findings underscore the role of cancer treatments as an etiological factor for POI and emphasize the importance of recognizing the risk of POI in cancer survivors for early diagnosis and intervention.

Long‐term outcomes of fertility‐sparing treatment in endometrial carcinoma and endometrial intraepithelial neoplasia: Recurrence risk factors over a 9‐year follow‐up

AbstractIntroductionFertility‐sparing treatments using oral progestins have demonstrated promising oncologic outcomes for endometrial intraepithelial neoplasia and early‐stage endometrial cancer. However, the high recurrence rate remains a major concern, and the literature on long‐term follow‐up outcomes is limited. This study aimed to identify recurrence risk factors by analyzing clinicopathological and molecular profiles in a cohort with a median follow‐up of 9 years.Material and MethodsThis retrospective study included patients under 45 years of age who were diagnosed with endometrial intraepithelial neoplasia or endometrial cancer and received fertility‐sparing treatments at our center between 2010 and 2021. Patients who achieved complete responses were categorized according to recurrence status. Demographic, clinical, and molecular data were compared between groups. The primary endpoint was to identify risk factors for recurrence; secondary endpoints assessed obstetric and oncologic outcomes in patients with relapse.ResultsOut of 40 patients, 8 underwent hysterectomy within 1.5 years, while 32 responded to treatment and continued follow‐up. The recurrence and non‐recurrence groups contained 20 and 12 patients, respectively, with a median follow‐up of 107.5 months (range, 35–175 months). Multivariate analysis showed that a family history of cancer (HR = 2.597, p = 0.039) and treatment with megestrol acetate as the initial therapy (HR = 3.130, p = 0.021) were independent risk factors for shorter time to recurrence. Although mismatch repair deficiency was positively correlated with recurrence, the association did not reach statistical significance (p = 0.057). Four out of 24 patients were upstaged after hysterectomy, and all were in the recurrence group. Nine patients (22.5%) achieved pregnancy, with three successfully conceiving after achieving complete response following retreatment.ConclusionsIn patients with long‐term follow‐up after fertility‐sparing treatment, a family history of cancer and initial treatment with megestrol acetate were significantly associated with recurrence.

TP53 mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma

AbstractIntroductionVulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways—one involving high‐risk human papilloma virus infection (HPV‐associated), and the other without HPV infection (HPV‐independent) often involving TP53 mutation. HPV‐associated VSCC generally has a better progression‐free survival than HPV‐independent VSCC. The aim of this study was to determine TP53 mutation status using immunohistochemistry, compare different methods of HPV detection and correlate both with survival in a retrospective cohort of 123 patients with VSCC.Material and methodsImmunohistochemistry for p53, Ki67 and p16INK4A (a surrogate marker for HPV infection) was performed on formalin‐fixed paraffin‐embedded tissues from a cohort of surgically treated VSCC patients to identify molecular subtypes of VSCC. Presence of HPV infection was detected by HPV DNA PCR and HPV mRNA in situ hybridization (ISH). The Pearson chi‐square test and multivariable Cox regression model were used to investigate the association of different parameters with progression‐free survival and disease‐specific survival (DSS), and Kaplan–Meier curves were used to show the association of different parameters with survival.ResultsThe results of p53 and p16INK4A immunohistochemistry confirmed three VSCC subtypes associated with different prognosis. The TP53 mutation status was identified as an independent prognostic factor of worse progression‐free survival (p = 0.024) after adjustment for FIGO stage. p16INK4A immunohistochemistry, mRNA ISH, and DNA PCR had excellent concordance in terms of HPV detection. According to the multivariable Cox regression model, the presence of hrHPV mRNA correlated significantly with increased progression‐free survival (p = 0.040) and DSS (p = 0.045), after adjustment for other confounders.Conclusionsp53 and p16INK4A immunohistochemistry stratify VSCC cohort into three subtypes with TP53mutated patients having the worst prognosis. The detection of hrHPV mRNA by ISH was an independent predictor of increased survival. Thus, the combined detection of p53 and HPV mRNA might improve risk stratification in VSCC.

Recurrent postmenopausal bleeding: Pathological findings and predictive factors. A multicenter, prospective, observational study

AbstractIntroductionRecurrent postmenopausal bleeding (PMB) occurs in 6%–25% of postmenopausal women who have experienced a previous episode of PMB. The question of whether recurrent PMB leads to a higher risk of endometrial cancer (EC) in comparison to a single episode of PMB is, however, controversial. Furthermore, little is known about predictive factors for recurrent PMB.Material and MethodsA multicenter prospective cohort study was conducted over a 5‐year period in four hospitals in the Netherlands. Women with PMB undergoing endometrial sampling and aged 40 years and older were included. Occurrence of recurrent PMB was retrospectively determined. Primary outcomes included (1) the incidence of recurrent PMB and (2) differences in pathological findings between patients with a single episode vs recurrent PMB. Secondary outcomes included (1) the association between diagnosis of benign polyps at first PMB and pathological findings at recurrent PMB and (2) factors predictive for recurrent PMB.ResultsA total of 437 women with PMB were included, of whom 360 were at risk of recurrent PMB. With a median follow‐up of 61 months (IQR (Interquartile range) 44–73), 26.4% experienced recurrent PMB. Patients with recurrent PMB were more often diagnosed with benign polyps (34.7% vs. 25.1%, p‐value 0.015) and less frequently with a malignancy (5.3% vs. 17.8%, p‐value 0.015), compared to patients with a single episode of PMB. Benign polyps at initial PMB were not associated with a (pre)malignancy at recurrence (OR 4.16, 95% CI 0.75–23.03). Predictive factors for recurrent PMB included use of hormone replacement therapy (HRT) (OR 3.32, 95% CI 1.64–6.72), and benign polyps at initial PMB (OR 1.80, 95% CI 1.07–3.04).ConclusionsRecurrent PMB is common in women with a previous episode of PMB. Compared to patients with a single episode of PMB, patients with recurrent PMB and benign histological outcomes at accurate workup during their first episode were less often diagnosed with malignancies and more frequently with benign polyps. Benign polyps at first PMB are predictive for recurrent PMB, but not for a higher risk of (pre)malignancy.

vNOTES retroperitoneal sentinel lymph node dissection for endometrial cancer staging: First multicenter, prospective case series

AbstractIntroductionThe current standard treatment for endometrial cancer is a laparoscopic hysterectomy with adnexectomies and bilateral sentinel node resection. A retroperitoneal vNOTES sentinel node resection has several theoretical potential advantages. These include being less invasive, leaving no visible scars, operating without Trendelenburg, and therefore offering the anesthetic advantage of easier ventilation in obese patients and following the natural lymph node trajectory from caudally to cranially and therefore a lower risk of missing the sentinel node. The aim of this study is to determine the feasibility of a retroperitoneal vNOTES approach to sentinel lymph node dissection for staging of endometrial cancer.Material and methodsA prospective multicenter case series was performed in four hospitals. A total of 64 women with early‐stage endometrial carcinoma suitable for surgical staging with sentinel lymph node removal were operated via a transvaginal retroperitoneal vNOTES approach. The paravesical space was entered through a vaginal incision after injecting the cervix with indocyanine green. A vNOTES port was placed into this space and insufflation of the retroperitoneum was performed. Sentinel lymph nodes were identified bilaterally using near‐infrared light followed by endoscopic removal of these nodes.ResultsA total of 64 women with early‐stage endometrial cancer underwent sentinel lymph node removal by retroperitoneal vNOTES technique. All patients also underwent subsequent vNOTES hysterectomy and bilateral salpingo‐oophorectomy. The median age was 69.5 years, median total operative time was 126 min and the median estimated blood loss was 80 mL. In 97% of the cases bilateral sentinel nodes could be identified. A total of 60 patients had negative sentinel nodes, three had isolated tumor cells and one had macroscopically positive sentinel nodes. No complications with sequel occurred.ConclusionsThis prospective multicenter case series demonstrates the feasibility of the vNOTES approach for identifying and removing sentinel lymph nodes in women with endometrial carcinoma successfully and safely. vNOTES allows sole transvaginal access with exposure of the entire retroperitoneal space, following the natural lymph trajectory caudally to cranially, and without the need for a Trendelenburg position.

Implementation of opportunistic salpingectomy for ovarian cancer prevention: Analyzing clinical practice and key characteristics

AbstractIntroductionOvarian cancer (OC) is the most lethal gynecologic cancer, often diagnosed at an advanced stage due to nonspecific symptoms and lack of effective screening. Over 90% of all ovarian cancer cases are epithelial in origin, which is thought to originate from the fallopian tubes in approximately 70% of cases. Opportunistic salpingectomy (OS), the additional removal of fallopian tubes during abdominal surgery, has emerged as a preventive strategy. Despite growing evidence, the implementation of OS varies widely. This study examines OS counseling and performance trends in the Netherlands from 2019 to 2022 and identifies associated patient, surgical, physician, and institutional characteristics.Material and MethodsA historical cohort study was performed, analyzing electronic medical records from six Dutch hospitals, including two academic, two teaching, and two nonteaching hospitals. Patients undergoing elective gynecologic surgery from January 2019 to December 2022 were considered eligible. Multilevel logistic regression analyses identified characteristics associated with counseling and performance of OS.ResultsOut of 2716 eligible patients, 51% were counseled about OS, of whom 92% opted for the procedure. The counseling rate increased from 38% in 2019 to 57% in 2022, while the performance rate rose from 39% to 56%. OS was more common among patients undergoing hysterectomy, laparoscopic surgery, and treatment at teaching hospitals. OS was less common during vaginal surgery. Physician characteristics accounted for 18% of counseling and 12% of performance variations.ConclusionsAlthough OS implementation improved, substantial variability remains in counseling and performance, largely driven by surgical approach and type of surgery. Targeted interventions to enhance uptake among underutilized surgical types, including vaginal procedures, are necessary to standardize OS practice and ensure wider adoption across all eligible patients.

Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: A systematic review and meta‐analysis

AbstractIntroductionOur objective was to conduct a systematic review and meta‐analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR).Material and methodsThis study followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement for systematic reviews and meta‐analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle–Ottawa Scale and the Methodological Index for Non‐randomized Studies was used for quality assessment. The primary end points for this meta‐analysis were complete response (CR), pregnancy, and live birth rates following HR‐based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR).ResultsTwenty‐one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR‐based conservative treatment were included for this systematic review. CR to HR‐based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth).ConclusionsHysteroscopic resection followed by progestins appears to be a promising choice for fertility‐sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.

The role of multiple high‐risk human papillomavirus infection on the persistence recurrence of high‐grade cervical lesions after standard treatment: A systematic review and a meta‐analysis

AbstractIntroductionThe role of multiple high‐risk human papillomavirus (HR‐HPV) infections on the occurrence of persistence/recurrence of high‐grade squamous intraepithelial lesion (HSIL) after conization/surgery for cervical intraepithelial neoplasia was evaluated.Material and methodsA systematic search of Pubmed/Medine, Scopus, Cochrane databases from inception to June 30, 2023 was performed. Three reviewers independently screened the abstracts of the selected studies and extracted data from full‐text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method. PROSPERO registration number CRD42023433022.ResultsOut of 1606 records screened, 22 full text articles met the inclusion criteria. A total of 8321 subjects treated (loop electrosurgical excision, laser or surgery) because of HSIL were followed‐up and included in the meta‐analysis. The pooled prevalence of overall persistence and/or recurrence was 17.6 (95% CI: 12.3–23.5) in multiple and 14.3 (95% CI: 10.1–19.2) in single HR‐HPV infections detected shortly before or at surgery. The pooled rate of multiple HR‐HPV infections was 25% (95% CI: 20.4–30). The odds ratio of histologically confirmed HSIL persistence and/or recurrence was significantly higher (OR: 1.38, 95% CI:1.08–1.75, p = 0.01, heterogeneity = 39%) among multiple than single HR‐HPV infections. Increased risk of HSIL persistence/recurrence was more marked among studies with multiple HR‐HPVs prevalence ≥25% (12 studies, N = 3476) (OR: 1.47, 95% CI: 1.18–1.84, heterogeneity = 0%) and in those evaluating true histologically confirmed recurrence after at least 6 months of negative follow‐up (9 studies, N = 5073) (OR: 1.67, 95% CI: 1.17–2.37, heterogeneity = 37%). Multiple HR‐HPVs infection detected during follow‐up visits had no effect on the risk of recurrence although the number of included studies was small (4 studies, N = 1248) (OR: 0.98, 95% CI: 0.68–1.39, heterogeneity = 0%). The risk of bias was rated as high in 10 and low‐moderate in 12 studies, respectively. In subgroup analysis, the risk of bias of the included studies (low/moderate vs. high), had a small, although not significant effect on the odds ratios of persistence/recurrence of HSIL (OR: 1.57, 95% CI: 1.23–2 for low‐moderate risk of bias and OR: 1.06, 95% CI: 0.65–1.75 for high risk of bias; p‐value for subgroup differences = 0.17).ConclusionsMultiple HR‐HPVs infections at the time of standard treatment of HSIL entail a small but significant increased risk of persistence/recurrence of HSIL and should be taken into account in the follow‐up plan.

Association of oral contraceptives and risk of endometrial cancer: A systematic review and meta‐analysis

AbstractIntroductionAlthough the relationship between the use of oral contraceptives and reduced endometrial cancer risk has now long been established, the need for female patients to be informed on this matter based on the latest results of scientific research remains. To help the evidence‐based decision‐making of women when choosing contraception methods, we aimed to provide them with an up‐to‐date overview and summary of past and recent findings on the association between the use of oral contraceptives and endometrial cancer risk.Material and MethodsThis study was registered in PROSPERO: CRD42022379871. PubMed, Embase, and Cochrane Library databases were searched on the December 5, 2022, to identify eligible articles. We included all experimental and observational studies that reported the number of users and non‐users of oral contraceptives among patients diagnosed or not with endometrial cancer. Data were extracted, and random‐effects meta‐analysis was performed to obtain summary odds ratios (OR) with 95% confidence intervals (CI). Heterogeneity across studies was assessed using Higgins & Thompson's I2 statistic.ResultsFifty‐six studies were eligible for qualitative synthesis, of which twenty‐five were eligible for quantitative analysis. The use of oral contraceptives was inversely associated with the odds of having endometrial cancer (OR = 0.61, CI: 0.46–0.80). The long‐term use of oral contraceptives led to the greatest odds reduction in having endometrial cancer (≥10 years: OR = 0.31, CI: 0.13–0.70), while shorter periods were also associated with a significant decrease in these odds, although to a lesser extent (≥5 years: OR = 0.39, CI: 0.23–0.64; <5 years: OR = 0.66, CI: 0.48–0.91).ConclusionsThe administration of oral contraceptives is time dependently associated with lower odds of having endometrial cancer, suggesting a protective association between the use of oral contraceptives and endometrial cancer.

The value of human epididymis 4, D‐dimer, and fibrinogen compared with CA 125 alone in triaging women presenting with pelvic masses: a retrospective cohort study

AbstractIntroductionCA 125, the biomarker in common clinical use for ovarian cancer, is limited by low sensitivity for early disease and high false positives. The aim of this study was to evaluate several candidate biomarkers, alone or in combination, compared with CA 125 in the prediction of malignant/borderline vs benign tumor status in premenopausal and postmenopausal women with pelvic masses.Material and methodsThis was a retrospective observational cohort study set in St James’s Hospital, a tertiary referral center for gynecological malignancy in Dublin, Ireland. Women undergoing surgery for pelvic masses between 2012 and 2018 were included. Preoperative human epididymis protein 4 (HE4), the Risk of Ovarian Malignancy Algorithm, the Risk of Malignancy Index I and II, D‐dimer, and fibrinogen were assessed. Logistic regression models were fitted for each biomarker alone and in combination. Receiver operating characteristics‐area under the curve (ROC‐AUC) and partial AUCs in the 90%‐100% specificity range were determined.ResultsIn all, 89 premenopausal and 185 postmenopausal women were included. In premenopausal women, no biomarker(s) outperformed CA 125 (AUC 0.73; 95% CI 0.63–0.84). In postmenopausal women, HE4 had a partial AUC (pAUC) of 0.71 (95% CI 0.64–0.79) compared with 0.57 (95% CI 0.51–0.69) for CA 125 (p = 0.009). HE4 + D‐dimer had an improved pAUC of 0.74 (95% CI 0.68–0.81, p < 0.001) and HE4 + D‐dimer + fibrinogen had a pAUC of 0.75 (95% CI 0.68–0.82).ConclusionsA novel biomarker panel of HE4 ± D‐dimer ± fibrinogen outperformed CA 125 alone as a high‐specificity biomarker in postmenopausal women and could aid in the preoperative triaging of pelvic masses. No biomarker(s) outperformed CA 125 in premenopausal women.

Preoperative and intraoperative assessment of myometrial invasion in endometrial cancer—A Swedish Gynecologic Cancer Group (SweGCG) study

AbstractIntroductionDeep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice.Material and methodsThis is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I‐III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard.ResultsIn the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively.ConclusionsIn Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI.

Survey of practices in the European Federation for Colposcopy: HPV vaccination after treatment for cervical precancerous lesions

AbstractIntroductionPatients treated for cervical precancerous lesions have a long‐term increased risk for cervical cancer compared with the general population. As human papillomavirus (HPV) vaccination is effective in preventing cervical cancer and its precursors when given prior to sexual debut, adjuvant HPV vaccination in relation to the treatment of precursor lesions has been of great interest. Existing supporting data are of low quality, and recent meta‐analyses called for high‐quality randomized controlled trials. The European Federation for Colposcopy (EFC) observed a heterogeneity in clinical practices of adjuvant vaccination, and this survey aimed to assess potential differences in vaccination practices across Europe.Material and MethodsA survey was sent out to 100 representatives of the 32 member countries of the EFC. The survey was in English and contained questions on current general HPV vaccination programs, whether guidelines on vaccination after treatment exist, and questions on respondents' own practices of recommending vaccination after treatment. The survey was constructed using the Google Forms web platform and sent by email to representatives of each National Colposcopy Society.ResultsIn total, 44 answers from 32 different European countries were received. Overall, 12 countries (12/32, 37.5%) reported having a national guideline on HPV vaccination at the time of treatment for precursor lesions, and in nine of these countries, adjuvant HPV vaccination is recommended. A third, 31.8%, of respondents (14/44) found the available evidence sufficient to recommend vaccination at the time of treatment, and 54.5% (24/44) found the evidence to be nearly sufficient. Only 13.6% (6/44) of the respondents found the current evidence insufficient to be able to recommend vaccination. Altogether, 29.5% (13/44) of respondents would recommend vaccination, even if future randomized controlled trials would not show benefits.ConclusionsThe varying practices regarding adjuvant HPV vaccination across European countries are concerning and call for ethical evidence‐based practices across Europe and reliance on high‐quality evidence to assess whether vaccination at the time of treatment is effective.

Risk factors for lymph ascites after surgery for endometrial cancer and impact on lymphedema of the legs. A prospective longitudinal Swedish multicenter study

AbstractIntroductionThe primary aim was to determine the occurrence of lymph ascites 4–6 weeks after surgery for endometrial cancer. Secondary aims were to assess risk factors for lymph ascites and the association with lymphedema of the legs.Material and MethodsThis was a post hoc analysis of an observational prospective multicenter study, performed in 14 Swedish hospitals that included 235 women undergoing surgery for early‐stage endometrial cancer between June 2014 and January 2018; 116 underwent surgery including pelvic and para‐aortic lymphadenectomy and 119 had surgery without lymphadenectomy. Lymph ascites (free intraabdominal fluid or encapsulated pelvic or para‐aortic fluid) was assessed by vaginal ultrasound 4–6 weeks postoperatively. Lymphedema was assessed using circumferential measurements of the legs preoperatively and 1 year postoperatively, enabling estimation of leg volume. A BMI‐standardized leg volume increase ≥10% was classified as lymphedema. Evaluation of risk factors was performed using multiple logistic regression.ResultsLymph ascites 4‐6‐weeks postoperatively occurred in 28.5% (67/235) of the women. The estimated volume of the lymph ascites in these women was mean 28 mL (standard deviation 48 mL) and median 14 mL (interquartile range 2–36 mL). Lymphadenectomy was a risk factor for lymph ascites (aOR 9.97; 95% CI 4.53–21.97) whereas the use of minimally invasive surgery (aOR 0.50; 95% CI 0.25–0.99) reduced the risk. Twenty‐two of 231 women (9.5%) developed lymphedema of the legs 1 year after surgery. The presence of lymph ascites was predictive of lymphedema (aOR 3.90; 95% CI 1.52–9.96).ConclusionsLymph ascites was common 4–6 weeks after surgery but in a low and clinically insignificant volume. Lymphadenectomy was a strong risk factor for lymph ascites and the use of minimally invasive surgery seemed to reduce the risk. Detection of lymph ascites at early postoperative follow‐up may be a means of selecting patients at high risk of developing lymphedema after treatment with endometrial cancer for preventive measures against lymphedema progression.

HPV vaccination following cervical intraepithelial neoplasia grade 2 diagnosis and risk of progression

Abstract Introduction Human papillomavirus (HPV) vaccination is associated with a significantly reduced risk of cervical cancer when administered before initial exposure to HPV. Women with high‐grade cervical intraepithelial neoplasia (CIN) have an increased risk of subsequent HPV‐related disease, including recurrent high‐grade CIN, compared to women without CIN. Some clinicians have advised women with high‐grade CIN to undergo HPV vaccination to reduce their subsequent risk, despite a lack of evidence for this practice. We aimed to evaluate whether HPV vaccination of women undergoing active surveillance for CIN grade 2 (CIN2) is associated with a decreased risk of progression to cervical intraepithelial neoplasia grade 3 or worse (CIN3+). Material and Methods We conducted a nationwide population‐based historical cohort study in Denmark on women aged 18–40 years undergoing active surveillance for CIN2 from 2007 to 2020. We compared women receiving at least one HPV vaccine dose within 6 months after their CIN2 diagnosis to women not receiving the vaccine. Our primary outcome was progression to CIN3+. We stratified by age at CIN2 diagnosis (18–29, 30–40), calendar year (2007–2012, 2013–2020), and index cytology (high‐grade, nonhigh‐grade). We used Cox proportional hazards regression to estimate hazard ratios of the outcomes with unvaccinated women as the reference. Age at diagnosis, calendar year, index cytology, income, and educational level were adjusted for. Results We included 4585 women, of whom 583 (12.7%) were vaccinated within 6 months after CIN2 diagnosis. A total of 1391 (30.3%) progressed to CIN3+ during follow‐up. The 5‐year cumulative risk was 29.9% (28.5–31.3). Overall, no protective effect of vaccination after CIN2 diagnosis was found (aHR 1.45 [1.24–1.69]). Stratified analyses showed increased progression risk with vaccination among women <30 years, in the early calendar period (2007–2012), and across both non‐high‐grade and high‐grade index cytology; no significant difference in risk was observed in women ≥30 years or in the latest calendar period (2013–2020). Conclusions HPV vaccination did not reduce the risk of progression in women undergoing active surveillance for CIN2. This finding indicates that HPV vaccination should not be recommended in this group of women.

Biopsy‐proven residual cervical cancer at the end of combined chemoradiation predicts poor outcome—Retrospective single‐center cohort study

Abstract Introduction Persistent tumor after combined chemoradiation for locally advanced cervical cancer is an established prognostic factor. Detection may include magnetic resonance imaging, positron emission tomography (PET) combined with CT scan, ultrasound, or biopsies; however, no agreement about the best method and time point has been reached. In our institution, a standardized biopsy protocol of at least four punch biopsies is routinely performed at the last brachytherapy with re‐biopsies 6 weeks later in cases not showing histologic complete response (hCR). This study aims to assess the prognostic relevance of these biopsies, especially with respect to the time point of hCR. Material and Methods This investigation was a retrospective single‐center observational cohort study that included all patients treated for locally advanced or node‐positive cervical cancer with combined chemoradiation at the University Hospital Innsbruck between 2008 and 2023. Patients with a hCR at the end of radiotherapy were classified as primary negative and otherwise as primary positive. Primary positive patients that achieved complete response at a control biopsy 6 weeks later were classified as secondary negative, and the remaining patients with residual tumor as secondary positive. Progression‐free survival (PFS) and overall survival (OS) were compared between all these groups. Results We included 184 patients in this study, from which 46 (25%) were classified as primary positive. These patients experienced a significantly worse PFS compared to primary negative patients ( p  = 0.008, HR = 2.03, 95% CI [1.20, 3.45]). The difference in PFS was also evidenced when comparing primary negative patients to those who had a hCR 6 weeks after radiotherapy (secondary negative) ( p  = 0.018, HR = 2.00, 95% CI [1.13, 3.56]). However, in primary positive patients, OS was not significantly reduced ( p  = 0.29, HR = 1.45, 95% CI [0.73, 2.86]). Conclusions Early response evaluation using punch biopsies at the time of the last brachytherapy can identify patients with residual tumor, which exhibit a statistically significant and clinically meaningful risk of disease progression. This risk was not reversed even in the case of a delayed hCR 6 weeks after completion of chemoradiation.

Incidence of and survival after surgical intervention for bowel obstruction in women with advanced ovarian cancer

AbstractIntroductionWomen with advanced ovarian cancer commonly present with peritoneal disease both at primary diagnosis and relapse, with risk of subsequent bowel obstruction. The aims of this study were to assess the cumulative incidence of and survival after intervention for bowel obstruction in women with advanced ovarian cancer, to identify factors predictive of survival and the extent to which the intended outcome of the intervention was achieved.Material and methodsWomen diagnosed with advanced ovarian cancer stages III and IV in 2009–2011 and 2014–2016 in the Stockholm‐Gotland Region in Sweden were identified in the Swedish Quality Registry for Gynecologic Cancer. Through hospital records, types of intended and executed interventions for bowel obstruction were assessed, and as well as when in the course of oncologic treatment, the intervention was performed. Time from first intervention to death was analyzed with survival methodology and proportional hazard regression was used.ResultsOf 751 identified women, 108 had an intervention for bowel obstruction. Laparotomy was the most prevalent intervention and was used in 87% (94/108) of all women, with a success rate of 87% (82/94). An intervention for bowel obstruction was performed before or during first line treatment in 32% (35/108) with a cumulative incidence in the whole cohort of 14% (108/751, 95% confidence interval [CI] 11–16). Median survival after intervention for bowel obstruction was 4 months (95% CI 3–6). The hazard of death increased when the intervention was performed after completion of primary treatment (HR 4.46, 95% CI 1.61–12.29, P < 0.01), with a median survival of 3 months. In women subjected to radical surgery during primary treatment, the hazard of death after intervention for bowel obstruction decreased (hazard ratio [HR] 0.54, 95% CI 0.32–0.91, P = 0.02).ConclusionsWomen with advanced ovarian cancer undergoing intervention for bowel obstruction have a dismal prognosis, regardless of which line of oncologic treatment the intervention was performed. In the majority of women an intervention for bowel obstruction was performed in a relapse situation with an even worse survival. Our findings emphasize the importance of a holistic approach in the decision‐making before an intervention for bowel obstruction in women with advanced ovarian cancer.

The effect of healthcare disruptions during the COVID ‐19 pandemic on colposcopy services and practice: A systematic review and meta‐analysis

Abstract Introduction The healthcare reorganization during the COVID‐19 pandemic affected colposcopy services and cervical cancer prevention, particularly in those countries where healthcare systems were already under‐resourced. This review aimed to quantify the reduction in colposcopy services across countries during the COVID‐19 pandemic and to determine whether the data source per study and cervical cancer screening coverage per country influenced the extent of these reductions. Material and Methods Studies reporting comparative data on colposcopy services between the COVID‐19 pre‐pandemic and pandemic period were included. MEDLINE, Embase, EMCare, Covid‐19 Research, British Nursing Index, APA PsycINFO, and Allied and Complimentary Medicine databases were searched for studies published from March 2020 to December 2023. The Newcastle−Ottawa scale was used for risk of bias assessment. The number of colposcopies, cervical treatments, pre‐invasive lesions diagnoses, and cervical cancer diagnoses per month were compared between the pre‐pandemic (before March 2020) and pandemic period (after March 2020). The effect measure was the standardized mean difference. Heterogeneity was evaluated with the chi‐squared test and quantified with the I 2 method. A meta‐regression was performed, considering the data source (regional/national databases/registries or institutional databases) and the screening coverage according to World Health Organization data (≥70% or <70%) as moderators. The review was registered on PROSPERO (CRD42023447188). Results Thirteen studies were included. Twelve were of good/high quality according to the Newcastle−Ottawa scale. The standardized mean difference between the pre‐pandemic and pandemic periods was −1.60 (95% CI −2.49 to −0.72, p  = 0.004) for colposcopies (4 studies, I 2  = 60.97%, p  = 0.075), −1.70 (95% CI −2.50 to −0.90, p  < 0.001) for cervical treatments (5 studies, I 2  = 52.92%, p  = 0.081), −4.61 (95% CI ‐7.90 to −1.33, p  = 0.006) for pre‐invasive lesion diagnoses (4 studies, I 2  = 92.45%, p < 0.001), and −0.85 (95% CI −1.52 to −0.19, p  = 0.012) for cervical cancer diagnoses (9 studies, I 2  = 71.07%, p  = 0.002). At meta‐regression, further reductions for cervical treatments and pre‐invasive lesion diagnoses were observed in the case of screening coverage <70%. Conclusions During the COVID‐19 pandemic, a reduction in colposcopies, cervical treatments, pre‐invasive lesions diagnoses, and invasive cancer diagnoses was observed. Since a screening coverage of <70% heightened these declines, increasing such coverage could lead to better resilience of cervical cancer prevention services to future crises.

Regional practice variation in hysterectomy and the implementation of less invasive surgical procedures: A register‐based study in the Netherlands

AbstractIntroductionMany women experience bleeding disorders that may have an anatomical or unexplained origin. Although hysterectomy is the most definitive and common treatment, it is highly invasive and resource‐intensive. Less invasive therapies are therefore advised before hysterectomy for women with fibroids or bleeding disorders. This study has two aims related to treating bleeding disorders and uterine fibroids in the Netherlands: (1) to evaluate the regional variations in prevalence and surgical approaches; and (2) to assess the associations between regional rates of hysterectomies and less invasive surgical techniques to analyze whether hysterectomy can be replaced in routine practice.Material and methodsWe completed a register‐based study of claims data for bleeding disorders and fibroids in women between 2016 and 2020 using data from Statistics Netherlands for case‐mix adjustment. Crude and case‐mix adjusted regional hysterectomy rates were examined overall and by surgical approach. Coefficients of variation were used to measure regional variation and regression analyses were used to evaluate the association between hysterectomy and less invasive procedure rates across regions.ResultsOverall, 14 186 and 8821 hysterectomies were performed for bleeding disorders and fibroids, respectively. Laparoscopic approaches predominated (bleeding disorders 65%, fibroids 49%), followed by vaginal (bleeding disorders 24%, fibroids 5%) and abdominal (bleeding disorders 11%, fibroids 46%) approaches. Substantial regional differences were noted in both hysterectomy rates and the surgical approaches. For bleeding disorders, regional hysterectomy rates were positively associated with endometrial ablation rates (β = 0.11; P = 0.21) and therapeutic hysteroscopy rates (β = 0.14; P = 0.31). For fibroids, regional hysterectomy rates were positively associated with therapeutic hysteroscopy rates (β = 0.10; P = 0.34) and negatively associated with both embolization rates (β = −0.08; P = 0.08) and myomectomy rates (β = −0.03; P = 0.82).ConclusionsRegional variation exists in the rates of hysterectomy and minimally invasive techniques. The absence of a significant substitution effect provides no clear evidence that minimally invasive techniques have replaced hysterectomy in clinical practice. However, although the result was not significant, embolization could be an exception based on its stronger negative association.

Validation of data quality in the Swedish quality register of gynecologic cancer for cervical cancer and vulvar cancer—a Swedish gynecologic cancer group (Swe‐GCG) study

AbstractIntroductionPopulation‐based registers provide an important source of real‐world data. The growing number of large cohort studies using data from cancer registers makes validation of such registers important. The Swedish Quality Register of Gynecologic Cancer (SQRGC) is a nationwide population‐based register containing data on patient and tumor characteristics, treatment, and follow‐up. To ensure that the results from research and quality assurance reports using SQRGC data are robust and reliable, the accuracy and completeness of the register need to be validated. The aim of this study was to evaluate the quality of data on cervical cancer and vulvar cancer in the SQRGC.Material and MethodsQuality of data in the SQRGC was investigated by evaluating completeness, timeliness, comparability, and validity in accordance with recommendations from the International Agency for Research on Cancer and the national Swedish guidelines on validation of cancer registers. Completeness was evaluated by coverage relative to the Swedish National Cancer Register, and timeliness as the time from diagnosis until entry into the SQRGC. We randomly selected 276 women diagnosed with cervical cancer (n = 138) and vulvar cancer (n = 138) between 2014 and 2019 for validation. An external monitor manually re‐abstracted data on 10 core variables per sub‐register from the patients' medical records. Comparability was assessed by reviewing the adherence to international standards regarding coding. Validity was evaluated by the agreement between re‐abstracted data and original data in the SQRGC. Correlations were estimated using Pearson's correlation coefficient and Cohen's kappa coefficient.ResultsFor cervical cancer, the completeness was 99% and the timeliness was 87.1% within 12 months. The corresponding figures for vulvar cancer were 100% and 87.9%, respectively. Adherence to international coding standards was satisfactory. The median degree of agreement between re‐abstracted data and data in the SQRGC was 90.8% (range 73.2%–100%) for cervical cancer, and 85.4% (range 59.6%–98.2%) for vulvar cancer.ConclusionsThe data on cervical and vulvar cancer in the SQRGC are of adequate quality and may well be used for research and clinical purposes.

Magnetic resonance guided high intensity focused ultrasound (MR‐HIFU) effectively reduces fibroid‐related symptoms and improves quality of life—A prospective single‐centre 12‐month follow‐up study

AbstractIntroductionUterine fibroids are the most common benign tumors among women, and it is estimated that approximately 70% of women have one or multiple fibroids by the age of menopause. About 30% of these women suffer from symptoms related to the fibroids. Magnetic resonance‐guided high‐intensity focused ultrasound (MR‐HIFU) is a novel, non‐invasive treatment method for symptomatic uterine fibroids.Material and MethodsIn this prospective, single‐centre follow‐up study, 175 women with symptomatic uterine fibroids were treated with MR‐HIFU. The effect of MR‐HIFU on fibroid symptoms and quality of life was evaluated using a uterine fibroid‐specific quality of life questionnaire (UFS‐QoL). The main outcome measure was the symptom severity score and quality of life (QoL) before the MR‐HIFU and 3 and 12 months after the treatment. This study was registered at clinicaltrials.gov (NCT03937401).ResultsThe median symptom severity score decreased from 56 (IQR 44–69) at baseline to 28 (IQR 16–44) at 3 months (p < 0.01) and 25 (IQR 16–38) at 12 months (p < 0.01) after treatment. The QoL score increased from a median of 48 (IQR 33–66) at baseline to 73 (IQR 59–93) at 3 months (p < 0.01) and 78 (IQR 66–90) at 12 months after treatment (p < 0.01). The reintervention rate during the 12‐month follow‐up was 2%.ConclusionsMR‐HIFU significantly reduces the severity of fibroid‐related symptoms in selected patients as early as 3 months after MR‐HIFU. The effect persists at 12 months. There is also a significant improvement in the quality of life 3 months after treatment, which further increases at 12 months.

Ultrasound guided microwave ablation treatment of uterine fibroids: Clinical response and patient acceptability

AbstractIntroductionThe objective of this study was to evaluate the effectiveness and acceptability of ultrasound guided microwave ablation for treating symptoms related to uterine fibroids.Material and MethodsThis was a prospective interventional study. Patients with symptomatic uterine fibroids were included at Danderyd Hospital, Sweden, from January 2020 to August 2023. All patients were treated with percutaneous or vaginal ultrasound guided microwave ablation. Primary outcome was reduction of fibroid symptoms evaluated by the validated uterine fibroid symptom and quality of life (UFS‐QoL) questionnaire at 6 months post‐treatment. Location of each fibroid was noted. Secondary outcomes included reduction of menstruation blood loss, change in hemoglobin, ferritin and Anti‐Müllerian hormone, fibroid volume difference, hospitalization, acceptability, and postoperative pain. Clinical trials registration number NCT04240262.ResultsSymptoms from uterine fibroids decreased by 37% (p < 0.001) on the symptom severity scale and health‐related quality of life increased by 74% (p < 0.001). Menstrual blood loss decreased by 38% (p < 0.001) according to the Pictorial Bleeding Assessment Chart and median fibroid shrinkage of the three largest treated fibroids was 64% (p < 0.001). Highest median shrinkage rate (82) was seen in submucous fibroids. A total of 110 of 113 (97%) patients left the hospital on the day of treatment. We experienced one adverse event (0.8%) Clavien Dindo grade 3. Acceptability was high and postoperative pain was mild to moderate.ConclusionsMicrowave ablation is a highly acceptable minimally invasive method for treating symptoms related to uterine fibroids in patients who desire uterus preservation. Submucosal fibroids showed more favorable treatment results.

Self‐collected vaginal HPV samples for long‐term non‐attendees in the Swedish organized cervical cancer screening program

AbstractIntroductionMost cervical cancer cases in Sweden are diagnosed among women who have failed to attend screening. The objective of this study was to analyze the effectiveness of offering vaginal HPV (human papillomavirus) self‐samples to long‐term non‐attendees as a routine in this screening program, in which non‐attendees had already been the targets of several interventions.Material and MethodsRegister data from the organized cervical screening program were used in this population‐based study. From January 2016 to December 2019, 33 881 high‐risk (hr‐) HPV self‐sample kits were sent to the homes of long‐term screening non‐attendees (≥7 years without a registered screening test), aged between 29 and 64 years, in Region Västra Götaland, Sweden. All samples returned to the laboratory were analyzed with the Cobas HPV DNA assay (Roche) for HPV16, HPV18, and for 12 other hr‐HPV types. HPV‐positive women were referred for colposcopy. Compliance and results of follow‐up were assessed 12 months after HPV analysis. Descriptive statistics, trend analysis, and risk ratios were used to compare outcomes across groups.ResultsThe median age of invited women was 49 years; 35% had not been screened before. The response rate was 19.4% (6582/33881). The HPV prevalence was 12.0% (788/6582), and 80.2% of HPV‐positive women attended follow‐up. Women with no previous cervical sample had a lower response rate: 15.7% (RR (Risk ratio) 0.73 (95% CI (Confidence interval) 0.70–0.77)). They also had lower attendance in follow‐up when HPV‐positive (71.6% RR 0.86 (CI 0.78–0.94)), compared with women who had previous samples. The proportions of high‐grade histopathology (HSIL+) among followed‐up women were 31.3% for HPV16, 15.2% for HPV18, and 8.8% for HPVnon‐16/18. Nine cervical cancer cases were found among 6582 women, corresponding to a rate of 137 cases per 100,000 women.ConclusionsVaginal HPV self‐samples increased cervical screening attendance by almost one‐fifth among non‐attendees who had previously resisted several invitations and interventions. Biopsied women positive for HPV16 or HPV18 had a high prevalence of HSIL or cervical cancer, which strongly supports direct referral to colposcopy. Long‐term non‐attendees have an exceptionally high risk of cervical cancer and should receive special attention.

Outcomes associated with large loop excision of the cervical transformation zone in women 60–64 years of age: A population‐based register study from Denmark

AbstractIntroductionFor women treated for cervical dysplasia at 60–64 years in Denmark, we reported the frequency of abnormalities before and after treatment of cervix uteri (most frequently performed as large loop excision of the cervical transformation zone, LLETZ) using population‐based real‐world data.Material and MethodsWe conducted a retrospective cohort study based on national data from the Danish Pathology Data Bank and identified women who underwent a LLETZ in 2010–2016 at the age of 60–64. Women were managed according to nationwide evidence‐based recommendations proposed by the Danish professional organizations. We retrieved information on all LLETZ specimens, cervical histology, cytology, and human papillomavirus (HPV) tests in the period of 2 years prior to the procedure to 2 years thereafter. We reported the frequencies of abnormalities before, at, or after the procedure.ResultsOf the 1014 women who had a LLETZ during the study period, 660 (65%) showed cervical intraepithelial neoplasia grade 1 or worse (CIN1+, including CIN1, CIN2, CIN3, cervical cancer, and CIN not otherwise specified) in their LLETZ specimen, with free resection margins in 255 (39%). Of the 1014 women, 551 (54%) had CIN2+ in a biopsy preceding the LLETZ and in 567 (56%) CIN2+ was found in their LLETZ specimen. In 37 (4%) women, the specimen showed cervical cancer; whereas in the pre‐LLETZ biopsies of these 37 women, cancer was detected in only 7 (1%). After LLETZ, 818 (81%) women underwent test‐of‐cure follow‐up which was positive in 406 women (40%). Furthermore, 408 (40%) women had new histological samples registered after LLETZ. These showed CIN2+ in 134 (13%) women, whereas a new cancer was diagnosed in 11 (1%) women.ConclusionsDue to persistent abnormal tests after LLETZ, an extended follow‐up is still required for a large proportion of the women in this age group.

Predictors for regression and progression of actively surveilled cervical intraepithelial neoplasia grade 2: A prospective cohort study

AbstractIntroductionTo evaluate predicting clinical factors for regression and progression of cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) in young women during two years of active surveillance.Material and MethodsThis was a single‐center prospective observational cohort study. Women under 31 years of age giving written informed consent with histologically confirmed CIN2 were followed with colposcopy, cytology, and biopsies every 6 months up to 24 months. At baseline, HPV genotyping was performed on cervical samples. The rates of regression and progression were recorded for every timepoint and at the end of study overall and stratified according to clinical factors and HPV genotypes at baseline. Risk ratio (RR) was used to estimate the relative risks for regression and progression. The study was registered in the ISRCTN registry (ISRCTN91953024).ResultsIn total, 205/243 (84.4%) women completed the study. Complete regression (normal histology and/or normal or atypical squamous cells of undetermined significance (ASC‐US) cytology) was detected in 64.4.% (n = 132) while 16.1% (n = 33) of the lesions progressed to CIN grade 3 (CIN3) or worse including 31 CIN3 cases, one adenocarcinoma in situ and one cervical cancer case. Factors associated with progression were initial large (>50% of the transformation zone) lesion size, risk ratio (RR) 3.06 (95% confidence interval (CI) 1.40–6.69), and high‐grade referral cytology RR 4.73 (95% CI 1.18–19.03). Compared with baseline HPV negativity or having only low‐risk HPV genotypes present, high‐risk HPV (hrHPV) positivity was associated with lower likelihood of regression RR 0.74 (95% CI 0.60–0.91). Age, cigarette smoking, use of combined oral contraceptives or baseline high‐risk HPV genotype, including HPV16, were not associated with the outcomes.ConclusionsThe majority of CIN2 lesions regress in young women. Women with large lesions and/or high‐grade referral cytology should perhaps more often be treated instead of active surveillance. Initial hrHPV genotype does not appear to predict outcomes while not harboring hrHPV favors regression.

Microvascular flow imaging of fibroids: A prospective pilot study

AbstractIntroductionImaging fibroid vascularity may predict fibroid growth and aid to determine most appropriate therapy. Microvascular (MV) flow imaging is relatively new and is able to detect slow flow in small vessels. Data on feasibility, reproducibility, and reliability of MV‐flow imaging in fibroids is lacking. The purpose of our study was to determine the reproducibility of MV‐flow imaging and to explore this technique for clinical practice for assessing blood flow in fibroids.Material and MethodsThirty patients with one or multiple fibroids (diameter 1.5–12.0 cm) were prospectively included. Transvaginal ultrasound scanning was performed in B‐mode, 2D MV‐Flow™, 2D and 3D power Doppler mode (HERA W10, Samsung) by two experienced gynecologists at a tertiary care clinic from February to December 2021. The primary outcome was intra‐ and interobserver agreement of the vascular index (VI) and color score (CS). The following parameters: ‘2D MV‐flow VI’, ‘3DPD VI’, ‘2D MV‐flow CS’ and ‘2DPD CS’ were measured offline in the center, pseudocapsule, and entire fibroid. Secondary offline outcomes for exploring 2D MV‐flow for clinical practice, included (1) ability to discern vascular structures, (2) assessing the degree of vascularity via CS and calculating a VI, and (3) determining penetration depth of the ultrasound signal in both power Doppler and MV‐flow imaging.ResultsAll scans of the 30 included patients were of sufficient quality to analyze. Inter‐ and intra‐observer correlations of all studied parameters were good to excellent, both for 2D MV‐flow and 2D power Doppler (intercorrelation coefficient 0.992–0.996). Using 2D MV‐flow different vascular structures were visible in detail, in contrary to using 2D and 3D power Doppler. In significantly more fibroids central flow could be visualized using 2D MV‐flow (63%) than with 2D power Doppler (13%, p = 0.001). Finally, penetration of the ultrasound signal was deeper using 2D MV‐flow (3.92 cm) than with 2D power Doppler (2.95 cm, p = 0.001).ConclusionsUsing 2D MV‐flow imaging for determining vascularity is highly reproducible. It has potential added value for clinical practice as it depicts detailed vascular structures and the degree of vascularity, especially in the center of the fibroid.

Does HPV vaccination during periconceptional or gestational period increase the risk of adverse pregnancy outcomes?—An updated systematic review and meta‐analysis based on timing of vaccination

AbstractIntroductionThe human papillomavirus (HPV) vaccine is crucial in preventing cervical cancer, and a significant number of women in 135 countries worldwide may have unknowingly received the vaccine during peri‐pregnancy or pregnancy due to a lack of regular pregnancy testing. Previous studies on the safety of pregnancy outcomes with vaccination before and after pregnancy have not reached definitive conclusions. Thus, we subdivided the vaccination time frame and conducted an updated study to further examine whether exposure to the HPV vaccine during pregnancy or the periconceptional period increases the likelihood of adverse pregnancy outcomes.Material and MethodsThe clinical trials and cohort studies published before August 1, 2023, were retrieved from PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials. The Newcastle–Ottawa Scale and Cochrane risk of bias assessment tool were adopted to evaluate the risk of bias in the included studies. In addition, the quality assessment was carried out using the Review Manager 5.4 Software, and a meta‐analysis was conducted using the Stata 16 Software.ResultsEleven studies were located. The results showed that receiving 4vHPV during the periconceptional or gestational period had no relationship with an increased risk of spontaneous abortion, stillbirth, preterm birth, birth defects, small for gestational age, and ectopic pregnancy. Neither receiving 2vHPV nor 9vHPV was associated with a higher risk of stillbirth, preterm birth, birth defects, small for gestational age, and ectopic pregnancy; however, receiving 2vHPV during the period from 45 days before last menstrual period (LMP) to LMP and 9vHPV during the period from 90 days before LMP to 45 days after LMP seemed to be related to an increased risk of spontaneous abortion (RR = 1.59, 95% CI: 1.04–2.45, RR = 2.04, 95% CI: 1.28–3.24).ConclusionsIn conclusion, the likelihood of an elevated risk of spontaneous abortion caused by HPV vaccination during the periconceptional or gestational period could not be completely ruled out. Given the lack of evidence, further research is needed to examine the effect of HPV vaccination on spontaneous abortion.

Clinical impact of pre‐treatment FDG‐PET/CT staging of primary ovarian, fallopian tube, and peritoneal cancers in women

AbstractIntroductionTo assess the clinical impact of preoperative fludeoxyglucose (FDG) with positron emission tomography (PET) and computed tomography (CT) in women with ovarian, fallopian tube, or peritoneal cancer with focus on consequences of added findings (AFs).Material and methodsFDG‐PET/CT was implemented as a standard imaging modality for women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer at our institution in 2008. After full implementation, all preoperative scans were reviewed and AFs were evaluated from January 2011 to December 2012. Decisions regarding further examination made at the first multidisciplinary team conference were recorded. Subsequent procedures were tracked via medical records, and the impact of AFs on additional examinations, delay, and change in treatment plans was evaluated.ResultsForty‐four (21.1%) of 209 women presented with AFs. Further examination was performed in 35/44 (79.5%). Malignancy was identified in 15/35 (42.9%), revealing metastases from ovarian, fallopian tube, or peritoneal cancer in 11, a synchronous primary cancer in 3, and recurrence of a previous cancer in 1 woman. The ovarian, fallopian tube, or peritoneal cancer metastases were localized in the lungs, uterus, colon, vagina, and breasts. The remaining 20 AFs revealed 2 benign lesions and 1 pre‐malignant lesion, whereas no abnormality was found in 17. Further examination of AFs resulted in a significant time delay until treatment start of median 4 days (range 1‐83 days, P < 0.004).ConclusionsFurther examinations of AFs by FDG‐PET/CT delayed time to start of treatment by median 4 days in women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer in a contemporary institution with fast‐track access to additional diagnostics. The clinical implications of this must be balanced against the gain of detecting unrecognized malignancy in 15 of 209 women (7.2%).

Surgically treated ovarian lesions in preadolescent girls

AbstractIntroductionThe purpose of this study was to investigate the epidemiology and characteristics of surgically treated ovarian lesions in preadolescent girls.Material and methodsThis was a retrospective cohort study including all 0‐ to 11‐year‐old girls operated at a single center from 1999 to 2016 for ovarian cysts, neoplasms or torsions. Patient charts were reviewed for symptoms, preoperative radiological imaging, operative details and histopathology.ResultsWe identified 78 girls, resulting in a population‐based incidence of 4.2/100 000. Infants (n = 44) presented with benign cysts (42/44, 95%, one bilateral), a benign neoplasm (1/44, 2%) and a torsion without other pathology (1/44, 2%). Torsion was found in 25/29 (86%) ovaries with complex cysts and in 3/15 (21%) ovaries with simple cysts in preoperative imaging (P < 0.001). Most infants were symptomless. Lesions in 1‐ to 11‐year‐old girls (n = 34) included benign neoplasms (n = 21/34, 62%), malignant neoplasms (n = 5/34, 15%), a cyst with torsion (n = 1/34, 3%) and torsions without other pathology (n = 7/34, 21%). Torsion was more common in benign (17/21, 81%) than in malignant neoplasms (1/5, 20%) (P < 0.020). Ovarian diameter did not differ between ovaries with or without torsion (P = 0.238) or between benign and malignant neoplasms (P = 0.293). The duration of symptoms in lesions with or without torsion was similar.ConclusionsThe majority of surgically treated ovarian lesions in preadolescent are benign lesions with torsion. Surgery should be ovary‐preserving and performed without delay.

Oncologic outcomes after splenectomy during initial cytoreductive surgery in advanced epithelial ovarian cancer: a nationwide population‐based cohort study

AbstractIntroductionEpithelial ovarian cancer (EOC) patients undergoing splenectomy during cytoreductive surgery represent a small subgroup of patients. Splenic metastases or technical reasons due to extensive upper abdominal disease may require a splenectomy. It has been hypothesized that as the spleen’s antitumor immunologic functions may inhibit cancer growth, splenectomy may promote the growth of residual disease as observed in other cancer types of murine studies. The few studies assessing the impact of splenectomy on the oncologic outcomes of advanced stage EOC patients have reported inconsistent results. It remains unclear whether splenectomy during cytoreductive surgery is justified to achieve complete cytoreduction. The aim of this study was to assess the impact of a splenectomy on perioperative outcomes and survival of advanced stage EOC patients.Material and methodsIn this nationwide population‐based study, all consecutive patients diagnosed with FIGO stage IIIC and IV EOC between 1 January 2008 and 31 December 2015 were identified from the Netherlands Cancer Registry. Patients who underwent cytoreductive surgery combined with platinum‐based chemotherapy as primary treatment were selected. Differences in clinicopathologic characteristics between splenectomy and non‐splenectomy patients were assessed. Progression‐free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier survival curves and log‐rank tests. Cox proportional hazards models were used to adjust for covariates that influence survival.ResultsA total of 3911 patients were identified: 99 splenectomy and 3812 non‐splenectomy patients. Splenectomy patients were more likely to undergo extensive surgery or surgical reintervention, to receive intraperitoneal chemotherapy, intraoperative and postoperative blood transfusion, to experience postoperative infections, and to be admitted to an intensive care unit (all p < 0.002). No significant differences in PFS or OS were observed between splenectomy vs non‐splenectomy patients after adjusting for covariates.ConclusionsAlthough advanced stage EOC patients who undergo splenectomy during cytoreductive surgery have less favorable perioperative outcomes, no adverse impact of splenectomy on the survival of advanced stage EOC patients was observed. Splenectomy during cytoreductive surgery seems to be justified to achieve complete cytoreduction in advanced stage EOC patients.

The diagnostic accuracy of human epididymis protein 4 (HE4) for discriminating between benign and malignant pelvic masses: a systematic review and meta‐analysis

AbstractIntroductionMany women with benign pelvic masses, suspected of ovarian cancer, are unnecessarily referred for treatment at specialized centers. There is an unmet clinical need to improve diagnostic assessment in these patients. Our objective was to obtain summary estimates of the accuracy of human epididymis protein (HE4) for diagnosing ovarian cancer and to compare the performance of HE4 with that of cancer antigen 125 (CA125).Material and methodsWe searched PubMed, Ovid and Scopus using search terms for “pelvic masses” and “HE4”, to identify studies that evaluated HE4 for diagnosing malignant ovarian masses, in adult women presenting with a pelvic mass, suspected of ovarian cancer, and with diagnosis confirmed by histopathology. Screening, data extraction and Risk of Bias assessment with the QUADAS‐2 tool were done independently by two authors. We performed a meta‐analysis of the accuracy of HE4 and CA125 using a random‐effects bivariate logit‐normal model. A study protocol was registered at PROSPERO (CRD42020158073).ResultsIn the 17 eligible studies, which included 3404 patients, ovarian cancer prevalence ranged from 15% to 71%. Overall, the studies were heterogeneous. All studies seemed to have recruited patients in specialized settings. A meta‐analysis of seven HE4 studies resulted in a mean sensitivity of 79.4% (95% confidence interval [CI] 74.1%–83.8%) and a mean specificity of 84.1% (95% CI 79.6%–87.8%), for cut‐off values of 67–72 pmol/L. Based on eight studies, the mean sensitivity of CA125 was 81.4% (95% CI 74.6%–86.2%) and the mean specificity was 56.8% (95% CI 47.9%–65.4%), at a cut‐off of 35 U/ml. Given a 40% ovarian cancer prevalence, the positive predictive value (PPV) for HE4 would be 76.9% (71.9%–81.2%) vs 55.6% (50.2%–60.9%) for CA125. The negative predictive value (NPV) would be 85.9 (82.8%–88.6%) and 81.9% (76.2%–86.4%), respectively. At a 15% prevalence, the NPV would be 95.8% (95% CI 94.4%–96.7%) for HE4 and 94.4% (95% CI 92.3%–96.0%) for CA125. The PPV would be 46.9% (40.4%–53.4%) and 24.9% (21.1%–29.2%), respectively.ConclusionsHE4 had higher specificity and similar sensitivity compared with CA125. At high prevalence, PPV was also higher for HE4, but at low prevalence, it had a similar NPV to CA125. The field would benefit from studies conducted in general settings.

A prognostic system for epithelial ovarian carcinomas using machine learning

AbstractIntroductionIntegrating additional factors into the International Federation of Gynecology and Obstetrics (FIGO) staging system is needed for accurate patient classification and survival prediction. In this study, we tested machine learning as a novel tool for incorporating additional prognostic parameters into the conventional FIGO staging system for stratifying patients with epithelial ovarian carcinomas and evaluating their survival.Material and methodsCancer‐specific survival data for epithelial ovarian carcinomas were extracted from the Surveillance, Epidemiology, and End Results (SEER) program. Two datasets were constructed based upon the year of diagnosis. Dataset 1 (39 514 cases) was limited to primary tumor (T), regional lymph nodes (N) and distant metastasis (M). Dataset 2 (25 291 cases) included additional parameters of age at diagnosis (A) and histologic type and grade (H). The Ensemble Algorithm for Clustering Cancer Data (EACCD) was applied to generate prognostic groups with depiction in dendrograms. C‐indices provided dendrogram cutoffs and comparisons of prediction accuracy.ResultsDataset 1 was stratified into nine epithelial ovarian carcinoma prognostic groups, contrasting with 10 groups from FIGO methodology. The EACCD grouping had a slightly higher accuracy in survival prediction than FIGO staging (C‐index = 0.7391 vs 0.7371, increase in C‐index = 0.0020, 95% confidence interval [CI] 0.0012–0.0027, p = 1.8 × 10−7). Nevertheless, there remained a strong inter‐system association between EACCD and FIGO (rank correlation = 0.9480, p = 6.1 × 10−15). Analysis of Dataset 2 demonstrated that A and H could be smoothly integrated with the T, N and M criteria. Survival data were stratified into nine prognostic groups with an even higher prediction accuracy (C‐index = 0.7605) than when using only T, N and M.ConclusionsEACCD was successfully applied to integrate A and H with T, N and M for stratification and survival prediction of epithelial ovarian carcinoma patients. Additional factors could be advantageously incorporated to test the prognostic impact of emerging diagnostic or therapeutic advances.

BAG3 expression correlates with the grade of dysplasia in squamous intraepithelial lesions of the uterine cervix

AbstractIntroductionBcl‐2‐associated athanogene 3 (BAG3) is a protein involved in apoptosis and stress response, which is overexpressed in invasive cervical cancer. However, nothing is known about BAG3 expression in precancerous lesions of the uterine cervix. We aimed to evaluate the expression of BAG3 in cervical intraepithelial neoplasia/squamous intraepithelial lesions (CIN/SIL).Material and methodsForty patients (16 CIN1/L‐SIL, 11 CIN2/H‐SIL and 13 CIN3/H‐SIL) were assessed by immunohistochemistry for BAG3. The intensity of BAG3 expression was categorized as null, minimal, weak, moderate or strong. The association of BAG2 intensity of expression with the grade of dysplasia was assessed using Chi‐square test (significant P value <0.05).ResultsIn all normal controls, BAG3 expression was negative. In L‐SIL specimens, BAG3 expression was confined to the basal third of the epithelium, with an intensity minimal in nine cases (56.3%), weak in six (37.5%) and strong in one (6.3%). In H‐SIL specimens, BAG3 expression involved also the two upper thirds of the epithelium, with an intensity moderate in 13 cases (54.2%; 8 CIN2 and 5 CIN3) and strong in 11 cases (45.8%; 3 CIN2 and 8 CIN3). The distribution of BAG3 expression correlated perfectly with the grade of dysplasia (P = 0.0); a moderate/strong expression of BAG3 was significantly associated with H‐SIL (P < 0.0001), with no significant difference between CIN2 and CIN3 (P = 0.1228).ConclusionsIn CIN/SIL, both distribution and intensity of BAG3 expression correlate directly with the grade of dysplasia, supporting the involvement of BAG3 in all phases of cervical carcinogenesis and its possible diagnostic and prognostic role in cervical premalignant lesions.

The application of risk models based on machine learning to predict endometriosis‐associated ovarian cancer in patients with endometriosis

AbstractIntroductionThere is currently no satisfactory model for predicting malignant transformation of endometriosis. The aim of this study was to construct and evaluate a risk model incorporating noninvasive clinical parameters to predict endometriosis‐associated ovarian cancer (EAOC) in patients with endometriosis.Material and MethodsWe enrolled 6809 patients with endometriosis confirmed by pathology, and randomly allocated them to training (n = 4766) and testing cohorts (n = 2043). The proportion of patients with EAOC in each cohort was similar. We extracted a total of 94 demographic and clinicopathologic features from the medical records using natural language processing. We used a machine learning method – gradient‐boosting decision tree – to construct a predictive model for EAOC and to evaluate the accuracy of the model. We also constructed a multivariate logistic regression model inclusive of the EAOC‐associated risk factors using a back stepwise procedure. Then we compared the performance of the two risk‐predicting models using DeLong's test.ResultsThe occurrence of EAOC was 1.84% in this study. The logistic regression model comprised 10 selected features and demonstrated good discrimination in the testing cohort, with an area under the curve (AUC) of 0.891 (95% confidence interval [CI] 0.821–0.960), sensitivity of 88.9%, and specificity of 76.7%. The risk model based on machine learning had an AUC of 0.942 (95% CI 0.914–0.969), sensitivity of 86.8%, and specificity of 86.7%. The machine learning‐based risk model performed better than the logistic regression model in DeLong's test (p = 0.036). Furthermore, in a prospective dataset, the machine learning‐based risk model had an AUC of 0.8758, a sensitivity of 94.4%, and a specificity of 73.8%.ConclusionsThe machine learning‐based risk model was constructed to predict EAOC and had high sensitivity and specificity. This model could be of considerable use in helping reduce medical costs and designing follow‐up schedules.

Complications after advanced ovarian cancer surgery—A population‐based cohort study

AbstractIntroductionSurgical complications after primary or interval debulking surgery in advanced ovarian cancer were investigated and associations with patient characteristics and surgical outcomes were explored.Material and methodsA population‐based cohort study including all women with ovarian cancer, FIGO III–IV, treated with primary or interval debulking surgery, 2013–2017. Patient characteristics, surgical outcomes and complications according to the Clavien–Dindo (CD) classification system ≤30 days postoperatively, were registered. Uni‐ and multivariable regression analyses were performed with severe complications (CD ≥ III) as endpoint. PFS in relation was analyzed using the Kaplan–Meier method.ResultsThe cohort included 384 women, where 304 (79%) were treated with primary and 80 (21%) with interval debulking surgery. Complications CD I–V were registered in 112 (29%) patients and CD ≥ III in 42 (11%). Preoperative albumin was significantly lower in the CD ≥ III cohort compared with CD 0–II (P = 0.018). For every increase per unit in albumin, the risk of complications decreased by a factor of 0.93. There was no significant difference in completed chemotherapy between the cohorts CD 0–II 90.1% and CD ≥ III 83.3% (P = 0.236). In the univariable analysis; albumin <30 g/L, primary debulking surgery, complete cytoreduction and intermediate/high surgical complexity score (SCS) were associated with CD ≥ III. In the following multivariable analysis, only intermediate/high SCS was found to be an independent significant prognostic factor. Low (n = 180) vs intermediate/high SCS (n = 204) showed a median PFS of 17.2 months (95% confidence interval [CI] 15.2–20.7) vs 21.5 months (95% CI 18.2–25.7), respectively, with a significant log‐rank; P = 0.038.ConclusionsAdvanced ovarian cancer surgery is associated with complications but no significant difference was seen in completion of adjuvant chemotherapy when severe complications occur. Importantly, our study shows that intermediate/high SCS is an independent prognostic risk factor for complications. Low albumin, residual disease and primary debulking surgery were found to be associated with severe complications. These results may facilitate forming algorithms in the decision‐making procedure of surgical treatment protocols.

Claims for compensation from women with cervical cancer in Norway—A retrospective, descriptive study of a 12‐year period

AbstractIntroductionIn Norway, all patient‐reported claims for compensation are evaluated by The Norwegian System of Patient Injury Compensation (NPE). The number of claims from women with cervical cancer is rising, and the approval rate is high. Our aim was to study claims for compensation from women with cervical cancer to identify the type of failures, when, during the time‐course of treatment, the medical failures occurred, and the consequences of the failures.Material and methodsA retrospective, descriptive study of claims for compensation to NPE from cervical cancer patients during a 12‐year period, from 2007 through 2018. We used anonymized medical expert statements and summaries of NPE cases.ResultsIn all, 161 women claimed compensation for alleged medical failure related to cervical cancer. Compensation was approved for 100 (62%) women. Mean age at the time of alleged failure was 37.5 years (SD ±9.9). The main reasons why women sought medical attention were routine cervical screening (56%), or vaginal bleeding or discharge (30%). In approved cases, incorrect evaluation of cytology and histology was the cause of most failures (72%). Mean delay of cervical cancer diagnosis for approved cases was 28 months (SD ±22). Treatment not in accordance with guidelines was the cause of failure in 2% of the cases, and failure during follow up was the cause of failure in 12%. Consequences of the failures were as follows: worsening of cancer prognosis (89%), treatment‐induced adverse effects, such as loss of fertility (43%) and/or loss of ovarian function in premenopausal women (50%), and permanent injury after chemo‐radiation (27%). Seven women (7%) died, most probably as a consequence of the failure.ConclusionsThe main cause of medical failure in women with cervical cancer was incorrect pathological diagnosis. The main consequences of failures were worsening of cancer prognosis and treatment‐induced adverse effects. Increased focus on the quality of pathological examinations, and better routines in all parts of the cervical examinations might improve patient safety for women in risk of cervical cancer.

High‐grade cervical lesions after vaccination against human papillomavirus: A Danish cohort study

AbstractIntroductionIt is pertinent to evaluate the impact of vaccination against human papillomavirus (HPV) in real life. The aim of the study was to evaluate the real‐life impact of HPV vaccination in the first birth cohort of Danish women offered free HPV vaccination as girls and invited to screening at the age of 23 years.Material and methodsWomen born in 1993 were offered free HPV vaccination at the age of 15 years but women born in 1983 have never been offered free HPV vaccination. We followed these two birth cohorts for 10 years from the age of 15 to after their first invitation to screening, and compared the risk of high‐grade cervical intraepithelial neoplasia (CIN). Data were obtained from Danish national health registers.ResultsVaccination coverage was 91% in the 1993 birth cohort and <0.1% in the 1983 cohort. Screening coverage was close to 80% in both cohorts. CIN2+ was detected in 4% of the 15 748 screened women born in 1983 and in 3% of the 19 951 screened women born in 1993. The risk of high‐grade CIN was reduced by about 30% in the 1993 cohort compared with the 1983 cohort; for CIN2+ relative risk 0.74 (95% CI 0.66‐0.82) and for CIN3+ relative risk 0.68 (95% CI 0.58‐0.79).ConclusionsThis study investigated the real‐life impact of quadrivalent HPV vaccination by comparing a cohort of women offered HPV vaccination with a cohort of women not offered HPV vaccination. The observed decrease in the detection of high‐grade cervical lesions following HPV vaccination is in line with results from the randomized trials and has important implications for future cervical screening of HPV vaccinated cohorts.

Short‐term surgical complications after radical hysterectomy—A nationwide cohort study

AbstractIntroductionCentralization has, among other aspects, been argued to have an impact on quality of care in terms of surgical morbidity. Next, monitoring quality of care is essential in identifying areas of improvement. This nationwide cohort study was conducted to determine the rate of short‐term surgical complications and to evaluate its possible predictors in women with early‐stage cervical cancer.Material and methodsWomen diagnosed with early‐stage cervical cancer, 2009 FIGO stages IB1 and IIA1, between 2015 and 2017 who underwent radical hysterectomy with pelvic lymphadenectomy in 1 of the 9 specialized medical centers in the Netherlands, were identified from the Netherlands Cancer Registry. Women were excluded if primary treatment consisted of hysterectomy without parametrial dissection or radical trachelectomy. Women in whom radical hysterectomy was aborted during the procedure, were also excluded. Occurrence of intraoperative and postoperative complications and type of complications, developing within 30 days after surgery, were prospectively registered. Multivariable logistic regression analysis was used to identify predictors of surgical complications.ResultsA total of 472 women were selected, of whom 166 (35%) developed surgical complications within 30 days after radical hysterectomy. The most frequent complications were urinary retention with catheterization in 73 women (15%) and excessive perioperative blood loss >1000 mL in 50 women (11%). Open surgery (odds ratio [OR] 3.42; 95% CI 1.73‐6.76), chronic pulmonary disease (OR 3.14; 95% CI 1.45‐6.79), vascular disease (OR 1.90; 95% CI 1.07‐3.38), and medical center (OR 2.83; 95% CI 1.18‐6.77) emerged as independent predictors of the occurrence of complications. Body mass index (OR 0.94; 95% CI 0.89‐1.00) was found as a negative predictor of urinary retention. Open surgery (OR 36.65; 95% CI 7.10‐189.12) and body mass index (OR 1.15; 95% CI 1.08‐1.22) were found to be independent predictors of excessive perioperative blood loss.ConclusionsShort‐term surgical complications developed in 35% of the women after radical hysterectomy for early‐stage cervical cancer in the Netherlands, a nation with centralized surgical care. Comorbidities predict surgical complications, and open surgery is associated with excessive perioperative blood loss.

The added benefit of transvaginal sonography in the clinical staging of cervical carcinoma

AbstractIntroductionPatients diagnosed with cervical cancer face several treatment options, depending on the physical examination and the imaging modality results. Transvaginal sonography (TVS) was proposed as an imaging option to determine local spread of cervical tumors, along with magnetic resonance imaging, also by recently released International Federation of Gynecology and Obstetrics recommendations. We examined whether combined data from physical examination, high‐detail TVS, and positron emission tomography with 18F‐labeled fluoro‐2‐deoxyglucose and computed tomography (18F‐FDG PET/CT) may contribute to triage efficiency of cervical cancer patients.Material and methodsThis is a retrospective study of consecutive women diagnosed with cervical cancer at the Carmel Health Center, Haifa, Israel, during 2010‐2015. Inclusion criteria were histology of cervical cancer and the availability of three modalities—a thorough physical examination, a high‐detail TVS, and positron emission tomography (PET) with 18F‐FDG and computed tomography (18F‐FDG PET/CT). End points were the possibility to predict local invasion to the parametrium and distant lymph node metastasis at the time of triage to surgery or chemoradiation.ResultsSeventy‐three patients with cervical cancer were evaluated. TVS correctly predicted no involvement of the parametrium for the 25 who had a postoperative pathological report. TVS measurement of tumor dimension was also matched by the pathological report in these cases. Only three patients were referred for adjuvant therapy according to postoperative pathology criteria. Among 43 women treated with a combination of chemotherapy and radiotherapy due to advanced disease, and with complete data, at least two modalities were congruent with chemoradiation for 33 (77%). Three patients (7%) were referred to chemoradiation due to TVS result alone.ConclusionsThe combination of high‐detail TVS, directed to predict tumor dimensions and local spread, performed by a trained operator, combined with 18F‐FDG PET/CT and physical examination, can assist in selecting optimal treatment for cervical cancer patients, thus avoiding unnecessary operations.

Expectant management for early pregnancy miscarriage after radical trachelectomy: A single hospital‐based study

AbstractIntroductionWomen who have undergone radical trachelectomy as a fertility‐sparing treatment for early‐stage cervical cancer may be at higher risk for retained tissues after early‐term miscarriage due to cervical cerclage or cervical necrosis. Dilatation and curettage or aspiration may present additional risks in these women. The aim of this study was to assess the efficacy of expectant management for early pregnancy miscarriage after radical trachelectomy.Material and methodsKeio University Hospital records were reviewed for women who conceived after abdominal radical trachelectomy and received perinatal care between 1 April 2012 and 31 March 2020. A total of 62 women (76 pregnancies) were identified, and 13 of these women experienced miscarriage before 12 gestational weeks. The management and outcome of these cases were reviewed in detail.ResultsThe median maternal age at miscarriage was 39 years (range 31–42 years) and the median duration from abdominal radical trachelectomy to conception was 2.60 years (range 0.49–7.30 years). Cervical necrosis before conception occurred in one case (8%). One patient requested treatment with aspiration and the remaining 12 cases were managed with observation for a median of 23 days (range 7–50 days). There were no cases of endometritis or cases requiring dilatation and curettage for residue tissue. Further, no cases developed laceration of the residual cervix and no loss of cerclage sutures after discharge was noted.ConclusionsExpectant management seems to be safe and appropriate for first trimester miscarriage after abdominal radical trachelectomy.

Acceptability and feasibility of self‐sampling and follow‐up attendance after text message delivery of human papillomavirus results: A cross‐sectional study nested in a cohort in rural Tanzania

AbstractIntroductionThe objective was to determine if self‐collection of vaginal samples for human papillomavirus (HPV) testing was acceptable and feasible in rural Tanzania and to assess the extent of attendance at a follow‐up appointment among women who tested HPV‐positive after delivery of HPV results via text messages.Material and methodsA combined cross‐sectional and cohort study was conducted among women aged 25‐60 years from rural Kilimanjaro, Tanzania. Women were offered HPV self‐sampling or traditional visual inspection of the cervix with acetic acid. If HPV self‐sampling was preferred, participants received instructions on self‐collection with an Evalyn Brush. A questionnaire was used to assess the acceptability and feasibility of the self‐sampling procedure for the participants and delivery of HPV results via text messages. A mobile text message platform was used to send private text messages with the screening results to the participants.ResultsA total of 1108 women were enrolled and self‐collected an HPV sample; 11.8% tested positive for high‐risk HPV. The majority (98.9%) agreed that they had no trouble in understanding the instructions on how to perform the self‐collection and that they would recommend it to a friend (94.5%) or as a standard screening method in Tanzania (95.5%). A minority of women experienced bleeding (2.4%) or pain (6%) while collecting the sample, while some were worried that they would get hurt (12.7%) or felt embarrassed (3.5%). The majority (98.4%) of women would like to receive the screening test results via text messages. Eighty‐two per cent of those who tested positive for high‐risk HPV attended the follow‐up appointment after receiving a text message reminder and an additional 16% attended after receiving both a text message and a phone call reminder whereas 2% did not attend follow up at all. Attendance was not influenced by age, marital status, education level, parity, or HIV status.ConclusionsHuman papillomavirus self‐sampling and text‐message feedback delivery are generally well‐perceived and accepted among rural Tanzanian women, and the majority of HPV‐positive women attended a follow‐up appointment after receiving their HPV results and follow‐up appointment via text messages. This screening method may have potential to be transferrable to other low‐income countries with a high incidence of cervical cancer and so improve cervical cancer screening attendances.

The association between human papillomavirus and cervical high‐grade cytology among HIV‐positive and HIV‐negative Tanzanian women: A cross‐sectional study

AbstractIntroductionHuman papillomavirus (HPV) is the causative agent of precancerous lesions and cervical cancer, cervical cancer being the leading cause of deaths in Tanzanian women. Early detection and treatment of precancerous lesions are important in the prevention of cervical cancer cases.Material and methodsWe conducted a cross‐sectional study among 3390 Tanzanian women aged 25‐60 years. Information on lifestyle habits was collected, and women underwent gynecological examination with collection of cervical cells for conventional cytological and HPV testing. Blood samples were tested for HIV. The association between cervical high‐grade cytology (HGC) and potential risk factors was examined using multivariable logistic regression adjusting for age and high‐risk HPV (HR‐HPV).ResultsThe prevalence of HGC was 3.6% and of low‐grade cytology was 8.3%. In women who were both HR‐HPV‐positive and HIV‐positive, the prevalence of HGC was 28.3%. It increased by age and was 47% among women aged 50‐60 years. Women, who had their sexual debut at age 9‐15 years and 16‐18 years, respectively, had 2.5 and 2.4 times increased odds of HGC compared with women whose sexual debut was at age 21 years and older. HIV‐positive women had increased odds of HGC in comparison with HIV‐negative women after adjustment for age (odds ratio [OR] 2.95, 95% CI 1.92‐4.54). HR‐HPV‐positive women had nearly 100‐fold increased odds of HGC compared with HR‐HPV‐negative women (OR 96.6, 95% CI 48.0‐194), and this estimate was higher among HIV‐positive women (OR 152.2, 95% CI 36.1‐642.0).ConclusionsIncreasing age, early age at first intercourse, HR‐HPV, and HIV infections were associated with a substantially increased risk of HGC.

Agreement between careHPV and hybrid capture 2 in detecting high‐risk HPV in women in Tanzania

AbstractIntroductionVisual inspection of the cervix with acetic acid is used to control the burden of cervical cancer in low‐ and middle‐income countries. This method has some limitations and HPV DNA testing may be an alternative, but it is expensive and requires a laboratory setup. Cheaper and faster HPV tests have been developed. This study describe the agreement between a fast HPV test (careHPV) and hybrid capture 2 (HC2) in detection of high‐risk HPV among Tanzanian women.Material and methodsThe study involved women attending routine cervical cancer screening at the Ocean Road Cancer Institute and Kilimanjaro Christian Medical Centre in Tanzania. The women were offered HIV testing. Two cervical samples were subsequently obtained; the first sample was processed at the clinics using careHPV and the second sample was transported to Denmark and Germany for cytology and HC2 analysis. Kappa statistic was calculated to assess the agreement between careHPV and HC2. The sensitivity, specificity and predictive values of careHPV were calculated using HC2 as reference. The analyses were done for the overall study population and stratified by testing site and HIV status.ResultsA total of 4080 women were enrolled, with 437 being excluded due to invalid information, lack of careHPV or HC2 results. Overall agreement between the tests was substantial with a kappa value of 0.69 (95% confidence interval [CI] 0.66‐0.72). The sensitivity and specificity of careHPV was 90.7% (95% CI 89.6‐91.8) and 84.2% (95% CI 81.2–86.8), respectively. The agreement was similar in the stratified analyses where the kappa values were 0.75 (95% CI 0.70‐0.79) in women aged 25‐34, 0.66 (95% CI 0.62‐0.70) in women aged 35–60, 0.73 (95% CI 0.70‐0.77) at the Ocean Road Cancer Institute, 0.64 (95% CI 0.60‐0.69) at the Kilimanjaro Christian Medical Center, 0.73 (95% CI 0.68‐0.79) in HIV‐positive and 0.66 (95% CI 0.63‐0.70) in HIV‐negative women. The kappa value of 0.64 (95% CI 0.39‐0.88) for cervical high‐grade lesions indicates a substantial agreement between careHPV and HC2 in detecting HPV among women with cervical high‐grade lesions.ConclusionsA substantial agreement was found between careHPV and HC2 in detecting HPV overall as well as detecting HPV among women with cervical high‐grade lesions. However, given the limited resources available in low and middle‐income countries, the HPV testing assay should be weighed against the cost‐effectiveness of the test.

A walk‐in clinic as an alternative approach to reaching non‐attenders of the cervical cancer screening program in the North Denmark region—a pilot study

AbstractIntroductionUp to 39% of women in Denmark do not participate regularly in the cervical cancer screening program and initiatives to increase participation are called upon. The primary aim of this study was to describe previous screening history and characteristics of women attending screening in a walk‐in clinic. Furthermore, we wanted to investigate barriers to cervical cancer screening.Material and methodsWe designed a walk‐in clinic that was open 2 days a week from 16.00 to 19.00 h, located in the Departments of Gynecology in the two main hospitals of the North Denmark Region. The main purpose of the clinic was cervical cancer screening and the study period was 5 months. Women who were not eligible for screening or had other health complaints were referred to their general practitioner. The women included in the study, filled out a questionnaire regarding educational and occupational status; their screening history was registered using data from the Danish Pathology Register.ResultsDuring the study period, 255 women visited the walk‐in clinic. The final study population consisted of 249 women who met the inclusion criteria. Age range of participants was 23–77 years, with a median age of 45 years. The majority of the participants were currently employed (81%) or students (10%), the remaining being retired (5%) or unemployed (4%). Screening history showed that 138 (55.4%) of the women were on time for the screening or delayed less than 6 months compared to their recommended screening interval. Sixty‐one women (24.5%) were delayed >6 months but <2 years. Fifty women (20.1%) were classified as non‐attenders, with more than a 2‐year delay in their screening. In the group of non‐attenders, eight women had never been screened. Of the remaining 42 women, the median time since last screening was 8.2 years (range 5.0–25.3 years).ConclusionsWomen attending the walk‐in clinic tended to be primarily actively working or students (91%). All age groups in the screening population were represented. Screening history showed that 44.6% had not followed the recommended screening program.

Early‐stage endometrial cancer, CTNNB1 mutations, and the relation between lymphovascular space invasion and recurrence

AbstractIntroductionWomen diagnosed with early‐stage (FIGO 1) endometrial cancer, grade 1 and 2 can have a good prognosis. Most of these women can be treated successfully with a hysterectomy and bilateral salpingo‐oophorectomy and without the additional adjuvant treatment that is accompanied by more risks for complications. However, when recurrence does occur, the consequences can be dire. Accurate decisions must therefore be made by surgeons to avoid either under‐ or over‐treatment. Risk and patient stratification for tailoring treatment still need further improvement. Both histopathology and genetic variants could be integrated into the decision process if relevant factors were identified.Material and methodsMorphological features and the presence of selected genetic mutations in isolated malignant endometrial epithelial cells from these tumors were analyzed in a strictly defined cohort of FIGO 1, grade 1 and 2 low‐risk endometrial cancer. Their presence in this cohort, their relation to recurrence, and the association between histopathological features and mutations were determined. This analysis was performed using archival formalin‐fixed paraffin‐embedded tissue, complete re‐evaluation of histopathological features, laser capture microdissection of epithelial cells, and a polymerase chain reaction‐based mutational screening assay.ResultsTwenty‐one women with recurrence, after initial identification as low‐risk endometrial cancer, were compared with 20 matched control women. The histological marker of lymphovascular invasion was significantly associated with recurrence. There was also a very high prevalence of mutations in CTNNB1 gene, occurring in 50% of this cohort. PTEN mutations were also observed in 27.8% of cases and PIK3CA mutations in 22.2%; none of these mutations were significantly related to recurrence.ConclusionsThis study supports the importance of lymphovascular space invasion to identify women with significant risk for recurrence in initially low‐risk, early‐stage endometrial cancer. It also identifies CTNNB1 as a significant mutation in early‐stage disease, and although it may not represent a marker for recurrence its high prevalence in early stage disease could have relevance for both pathogenesis and early treatment.

Is it safe to preserve uterus after live birth following progestin‐based fertility‐sparing treatment for endometrial cancer or atypical hyperplasia: A long‐term retrospective cohort study

Abstract Introduction We aimed to assess the safety of continuous uterus‐preserving treatment among patients with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) who gave birth after progestin‐based fertility‐sparing treatment (FST). Material and Methods From January 2005 to June 2020, we conducted a retrospective cohort study at Peking University People's Hospital, China, comprising 212 patients with EC or AEH who underwent FST. The participants were categorized into two groups based on the reproductive outcome of live birth. Risk factors were analyzed for disease recurrence in the entire cohort, and additional analysis was conducted on postpartum recurrence specifically in the live birth group. Results Of 212 eligible patients, 73 had a live birth, and 139 did not have a live birth after FST. Multivariable Cox analysis showed that live birth significantly reduced the risk of disease recurrence (HR 0.326, p  = 0.011), while insulin resistance was identified as an adverse factor (HR 3.216, p  = 0.014). Except for two patients who underwent hysterectomy, among 71 patients undergoing uterus preservation after live birth, five (7%) patients experienced disease relapse (two EC and three AEH) after a median follow‐up of 26 (11, 47.5) months. Four out of these five patients with recurrence achieved a complete response after a second round of FST. Eight other patients (11.3%) experienced hyperplasia without atypical (EH) after live birth. Potential risk factors for postpartum recurrence of EC/AEH included irregular menstruation (80% vs. 39%; p  = 0.153), abnormal ultrasonographic findings (60% vs. 18.6%; p  = 0.065), and increased endometrial thickness (0.82 cm vs. 0.55 cm; p  = 0.017). While postpartum maintenance therapy was identified as a protective factor against recurrence (0% vs. 62.5%; p  = 0.012). Notably, patients with postpartum recurrence may achieve a complete response with repeat FST. Conclusions Although live birth was associated with improved recurrence‐free survival in patients with EC or AEH receiving FST, postpartum recurrence remains a concern. Irregular menstruation and abnormal ultrasound findings were identified as key risk factors for recurrence, while maintenance therapy exhibited a protective effect. These findings highlight the need for vigilant postpartum monitoring in this population.

Atypical placental site nodules: A retrospective case series

Abstract Introduction Atypical placental site nodule (APSN) is a rare diagnosis, representing remnants of a previous pregnancy and extravillous trophoblast tissue. These lesions are potential precursor lesions to rare forms of Gestational trophoblastic neoplasia (GTN). Recent data suggest up to a 15% risk of malignancy occurring either concurrently or manifesting within a few months of diagnosis. These patients are often young with future fertility considerations. Prognosis, treatment, and clinical follow‐up of APSN cases currently remain a matter of debate. This study aimed to address and explore some of these issues. Material and Methods Retrospective case series analysis was performed between 1st January 2000 and 31st December 2023 at the Sheffield Trophoblastic Disease Centre, Sheffield, UK. Patients on conservative management were asked at routine follow‐up telephone consultations if they would consider a completion hysterectomy in light of the risk of progression to GTN. Results Twenty‐two cases of APSN were registered, of which 10 (45%) received surgical management. Two (20%) cases were incidentally diagnosed following total abdominal hysterectomy (TAH) for other indications and eight (80%) had a TAH within twelve months of their initial diagnosis as part of primary management. None had histological evidence of GTN. Of the twelve (55%) patients initially opting primarily for conservative management, three (25%) decided to have a TAH performed based on the current evidence for risk of malignant transformation, eight (67%) indicated they would have a TAH based on advice from the center, and one (8%) was uncertain. No patients were diagnosed with GTN. Conclusions In this study, we found no evidence of malignant transformation in our patients, which conflicts with other published data conferring an 11%–14% risk of malignant transformation. An international consensus opinion needs to be reached within the Gestational trophoblastic community regarding the optimal advice, management, and follow‐up regimens for patients diagnosed with APSN.

Post robotic investment: Cost consequences and impact on length of stay for obese women with endometrial cancer

AbstractIntroductionThe aim of the study was to investigate whether robotic‐assisted surgery is associated with lower incremental resource use among obese patients relative to non‐obese patients after a Danish nationwide adoption of robotic‐assisted surgery in women with early‐stage endometrial cancer. This is a population‐based cohort study based on registers and clinical data.Material and methodsAll women who underwent surgery (robotic, laparoscopic and laparotomy) from 2008 to 2015 were included and divided according to body mass index (<30 and ≥30). Robotic‐assisted surgery was gradually introduced in Denmark (2008–2013). We compared resource use post‐surgery in obese vs non‐obese women who underwent surgery before and after a nationwide adoption of robotic‐assisted surgery. The key exposure variable was exposure to robotic‐assisted surgery. Clinical and sociodemographic data were linked with national register data to determine costs and bed days 12 months before and after surgery applying difference‐in‐difference analyses.ResultsIn total, 3934 women were included. The adoption of robotic‐assisted surgery did not demonstrate statistically significant implications for total costs among obese women (€3,417; 95% confidence interval [CI] −€854 to €7,688, p = 0.117). Further, for obese women, a statistically significant reduction in bed days related to the index hospitalization was demonstrated (−1.9 bed days; 95% CI −3.6 to −0.2, p = 0.025). However, for non‐obese women, the adoption of robotic‐assisted surgery was associated with statistically significant total costs increments of €9,333 (95% CI €3,729–€1,4936, p = 0.001) and no reduction in bed days related to the index hospitalization was observed (+0.9 bed days; 95% CI −0.6 to 2.3, p = 0.242).ConclusionsThe national investment in robotic‐assisted surgery for endometrial cancer seems to have more modest cost implications post‐surgery for obese women. This may be partly driven by a significant reduction in bed days related to the index hospitalization among obese women, as well as reductions in subsequent hospitalizations.

MiRNAs in endometrioid endometrial cancer metastatic loci derived from positive lymph nodes

AbstractIntroductionMicroRNAs (miRNAs) take part in tumorigenesis and show aberrant expression levels in cancerous tissues. We aimed to perform miRNA profiling of endometrioid endometrial cancer (EEC) metastatic loci derived from lymph nodes. Identification of aberrant miRNAs in positive lymph nodes could contribute to establishing new diagnostic markers and therapeutic targets.Material and methodsDuring the screening phase of the study, we performed profiling of 754 human miRNAs in endometrioid endometrial cancer tissues, microdissected metastatic loci from lymph nodes and healthy lymph nodes (Taqman Array). Selection of candidate miRNAs and subsequent validation using quantitative reverse transcription polymerase chain reaction (qRT‐PCR) in 50 tissue samples were performed.ResultsAfter the screening phase of the study, five miRNAs were selected (hsa‐miR‐18b, hsa‐miR‐148a‐5p, hsa‐miR‐204, hsa‐miR‐424, hsa‐miR‐129‐1‐3p). Validation revealed that miRNA‐204 and miRNA‐424 were highly downregulated in metastatic tissues compared with endometrial cancer samples (hsa‐miR‐204—P = .0008; hsa‐miR‐424—P = .0001). Receiver operating characteristic curves, which were constructed to compare endometrioid endometrial cancer and positive endometrioid endometrial cancer lymph nodes yielded the following area under the curves (AUCs): hsa‐miR‐204—.802 (96% confidence interval CI 0.676‐0.927), hsa‐miR‐424—.84 (95% CI 0.711‐0.969).ConclusionsCompared with primary endometrioid endometrial cancer tissue, metastatic loci derived from positive lymph nodes are characterized by profound downregulation of miRNA‐204 and miRNA‐424.

Improving imiquimod use in cervical high‐grade squamous intraepithelial lesions: A qualitative study

AbstractIntroductionTo investigate patient experiences and satisfaction with imiquimod for cervical high‐grade squamous intraepithelial lesions and its side effects, possibly influencing the (dis)continuation of treatment. Secondary objectives include evaluating patient counseling and guidance before and during imiquimod treatment for cervical high‐grade squamous intraepithelial lesions by gynecologists and nurse practitioners to improve patient guidance.Material and MethodsSemi‐structured interviews were conducted with patients treated with imiquimod for cervical high‐grade squamous intraepithelial lesions and with healthcare professionals from hospitals in the Netherlands. Interviews were transcribed and transcripts were analyzed using thematic analysis.ResultsA total of 15 patients, 11 of whom finished imiquimod treatment and four who discontinued imiquimod treatment, and six healthcare professionals were interviewed. Three main themes were identified: counseling and side effects, use of imiquimod, and contact moments during treatment. Many patients believed that sharing patient experiences would help in making treatment decisions. Patients discontinued treatment early due to side effects and the mode of application. Detailed information on application methods and side effect severity during counseling is desirable. Healthcare professionals agreed on the factors that need to be addressed during counseling but held different opinions on imiquimod's side effect severity and application methods.ConclusionsAdequate patient counseling on imiquimod treatment, including the possible application methods and potential side effects, along with optimal guidance during treatment, contributes to a better patient experience and reduces the likelihood of early discontinuation of treatment.

High rate of persistent HPV detection after diagnostic cervical excision in older screen‐positive women

AbstractIntroductionDiagnostic work‐up of older women with a positive cervical cancer screening test is often challenging due to incomplete visualization of the transformation zone. To reduce the risk of missing disease, a diagnostic cervical excision may be performed. However, little is known on treatment efficacy and post‐treatment surveillance for older women. We aimed to investigate the proportion of women testing negative for human papillomavirus (HPV) following a diagnostic cervical excision due to an abnormal screening test.Material and MethodsWe conducted a prospective cohort study on women aged ≥45 years who were referred for colposcopy due to an abnormal screening test between March 2019 and June 2021. All women had incomplete visualization of the transformation zone and underwent colposcopy and a diagnostic cervical excision at the first visit. Women were followed from date of excision until January 30, 2023. Follow‐up data was retrieved from the Danish Pathology Databank, and baseline characteristics were obtained from medical records. Cox regression was used on interval‐censored data to estimate crude and adjusted hazard ratios for a negative HPV test after cervical excision, stratified by histology and age.ResultsA total of 100 women underwent a diagnostic cervical excision and had at least one HPV test during follow‐up. Median age was 67.4 years, and median follow‐up time was 2.9 years. At the end of follow‐up, 70% tested HPV negative. Women with cervical intraepithelial neoplasia grade two or worse in their excision specimen were more likely to test HPV negative at the first test after cervical excision compared to women with less than cervical intraepithelial neoplasia grade two, however, not statistically significant (adjusted hazard ratio 1.69, 95% CI 0.92–3.10). Women aged 65–84 years were less likely to test HPV negative compared to women <65 years (adjusted hazard ratio 0.49, 95% CI 0.28–0.87).ConclusionsIn older women undergoing a diagnostic cervical excision, 70% tested HPV negative after 2.9 years, leaving 30% with persistent HPV positivity. More studies are needed to determine the risks associated with continued HPV positivity in the absence of high‐grade disease. Furthermore, given the absence of specific guidelines, the optimal surveillance frequency remains unknown.

Clinical performance of human papillomavirus based cervical cancer screening algorithm: The result of a large Danish implementation study

AbstractIntroductionIn Denmark, where human papillomavirus (HPV) ‐based cervical cancer screening is being implemented, the aim of this pilot implementation study was to test a specific screening algorithm, assess follow‐up examination attendance, and measure the proportion of precancer lesions found in relation to the number of women referred for colposcopy.Material and MethodsFrom May 2017 to December 2020, 36 417 women in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark, were included in the HPV group. Women positive for HPV16/18 irrespective of cytology and women positive for other high‐risk HPV (hrHPV) types having concomitant abnormal cytology were referred directly to colposcopy. Women positive for other hrHPV types and normal cytology were referred to repeat screening after 12 months, and hrHPV negative to routine screening after three years. We obtained information on screening results and subsequent histological diagnosis from the Danish Pathology Databank through September 2022.Results3.6% of the women were referred to colposcopy after primary screening, 5% to repeat screening after 12 months, and 91.4% back to routine screening. High follow‐up rates were observed: 96% attended colposcopy after primary screening, with 91% attending colposcopy after repeat screening. CIN3+ was detected at colposcopy following the primary screening in 28.1% of HPV16/18‐positive women and 18.2% of those positive for other hrHPV types with concomitant abnormal cytology. Of the women with other hrHPV and simultaneous ASCUS/LSIL, 8% had CIN3+. At the repeat screening, 43% had become hrHPV negative, 55% were persistently positive for other hrHPV, and 2% had turned positive for HPV16/18. At the colposcopy following repeat screening, 10.1% of the women positive for other hrHPV were diagnosed with CIN3+, in comparison with 11.1% of the HPV16/18‐positive women.ConclusionsIn this pilot implementation study, an algorithm for HPV‐based screening was evaluated in a Danish setting. The results demonstrated high attendance at follow‐up examinations and provided insights into the number of colposcopy referrals and the detection of CIN2 and CIN3+ cases. The results suggest that women testing positive for other hrHPV in combination with ASCUS/LSIL at primary screening could potentially be referred to repeat screening instead of an immediate colposcopy.

Trends and projections of ovarian cancer incidence in Hong Kong: A population‐based study

AbstractIntroductionThis study analyzed the incidence of ovarian cancer in Hong Kong and its association with age, calendar period and birth cohort, made projections through 2030, and attributed differences in new cancer cases to demographic and epidemiologic changes.Material and methodsIncidence data for ovarian cancer were obtained from the Hong Kong Cancer Registry. We employed the age‐period‐cohort modeling approach to investigate the association between ovarian cancer incidence and age in Hong Kong women, with particular emphasis on examining the changing trends of period and cohort effects on incidence. We projected the incidence of ovarian cancer in Hong Kong between 2018 and 2030 and attributed the rise in new cancer cases to epidemiologic and demographic shifts.ResultsBetween 1990 and 2017, a total of 11 182 women were diagnosed with ovarian cancer in Hong Kong. Crude and age‐standardized rates increased from 8.2 and 7.8 per 100 000 person‐years to 16.3 and 11.5 per 100 000 person‐years, respectively. New cases of ovarian cancer rose from 225 in 1990 to 645 in 2017. We observed an increased risk of ovarian cancer throughout the study period and in the post‐1940 birth cohort. The projected incidence rate and new cases of ovarian cancer are expected to continue growing due to demographic and epidemiologic changes such as fertility patterns and lifestyle factors, with an estimated 981 cases in 2030.ConclusionsThe period risk and cohort risk of ovarian cancer among Hong Kong women is increasing. Demographic and epidemiologic changes may continue to increase ovarian cancer incidence and new cases in Hong Kong.

Intraoperative use of tranexamic acid to reduce blood loss during cytoreductive surgery for advanced ovarian cancer: A randomized controlled clinical trial

AbstractIntroductionTranexamic acid reduces blood loss and allogeneic transfusion requirements in various surgical procedures. The role of tranexamic acid during cytoreductive procedures in advanced ovarian cancer is not clear.Material and methodsThis was a single center randomized, controlled, three‐armed clinical trial. A total of 150 ovarian cancer patients undergoing cytoreductive surgery were recruited and assigned to three groups (n = 50/group): the control group (normal saline), low‐dose group (10 mg/kg bolus + 1 mg/kg continuous infusion of tranexamic acid), and high‐dose group (20 mg/kg bolus + 5 mg/kg continuous infusion of tranexamic acid). The primary endpoint was intraoperative blood loss volume and total blood loss volume, and secondary endpoints included intraoperative blood transfusion volumes, vasoactive agent consumption, admission into the intensive care unit, and incidence of postoperative complications within postoperative 30 days. The study was registered at ClinicalTrials.gov ID: NCT04360629.ResultsThe patients in the high‐dose group had less intraoperative (median [IQR]: 625.3 mL [343.5–1210.5]) and total blood loss volume (748.9 mL [292.2–1650.2]) than those in the control group (1015.5 mL [679.4–1015.5], p = 0.012; and 1700.7 mL [458.7–2419.8], p = 0.004, respectively). In contrast, the intraoperative (992.5 mL [539.0–1404.0], p = 0.874) and total blood loss volume (1025.0 mL [381.8–1819.9], p = 0.113) was not significantly reduced in the low‐dose group when compared with the control group. Correspondingly, the relative risk of blood transfusion (RR [95% CI], 0.405 [0.180–0.909], p = 0.028) was reduced in the high‐dose group and required less intraoperative noradrenaline (881.0 ± 438.3 mg) to maintain stable hemodynamics than the control group (1548.0 ± 349.8 mg, p = 0.001). Furthermore, compared with the control group, the two tranexamic acid groups had decreased intensive care unit admission rates (p = 0.016) without increasing the incidence of postoperative seizure, acute kidney injury, and thromboembolism.ConclusionsHigh‐dose tranexamic acid is more effective in reducing blood loss and blood transfusion without increasing the risk of postoperative complications. The high‐dose regime tended to have a better risk–benefit profile.

Clinical characteristics and survival outcomes in patients with primary ovarian carcinoid: A historical cohort study

AbstractIntroductionPrimary ovarian carcinoids are extremely rare ovarian tumors, and there is limited data available on their clinical characteristics and survival outcomes.Material and methodsWe conducted a historical cohort study of 56 patients to investigate their clinical characteristics. The overall survival, disease‐specific survival, recurrence‐free survival, and potential prognostic factors of these patients were also evaluated.ResultsThe median age of these patients was 42.0 years (range: 20–71). The average mass and carcinoid size was 7.3 and 0.4 cm, respectively. Elevated tumor marker levels and ascites were observed in 15 and 10 patients, respectively. In 98.2% of the patients, tumors were confined to the ovary, while only one had metastatic disease. Surgery was the mainstay therapy: 37.5% of the patients underwent unilateral salpingo‐oophorectomy, 25.0% underwent hysterectomy with bilateral salpingo‐oophorectomy, 21.4% underwent ovarian cystectomy, 10.7% underwent comprehensive staging surgery, and 5.4% underwent bilateral salpingo‐oophorectomy. Appendectomy and lymphadenectomy were performed in eight and five patients, respectively, but none showed tumor involvement. Chemotherapy was the only adjuvant treatment utilized, and was administered in four patients. Pathological analysis showed that strumal carcinoid was the most predominant subtype, occurring in 66.1% of the patients. The Ki‐67 index was reported in 39 patients, 30 of which had an index of no more than 3%, with a maximum of only 5%. Only one relapse occurred after the initial treatment, and that patient experienced recurrences on two occasions, maintaining stable disease after surgery and octreotide therapy. After a median follow‐up of 3.6 years, 96.4% of the patients achieved no evidence of disease, while 3.6% were alive with the disease. The 5‐year recurrence‐free survival rate was 97.9% and no death occurred. No risk factors for recurrence‐free survival, overall survival, or disease‐specific survival were identified.ConclusionsThe Ki‐67 indices were extremely low and prognoses were excellent in patients with primary ovarian carcinoids. Conservative surgery, especially unilateral salpingo‐oophorectomy, is preferred. Individualized adjuvant therapy may be considered for patients with metastatic diseases.

Clinical characteristics and oncological outcomes of recurrent adult granulosa cell tumor of ovary: A retrospective study of seventy patients

AbstractIntroductionThis study aimed to describe the clinicopathological characteristics of recurrent adult granulosa cell tumor and identify the risk factors for recurrence.Material and methodsSeventy recurrent adult granulosa cell tumor patients treated in Peking Union Medical College Hospital between 2000 and 2020 were retrospectively reviewed. The primary outcomes were progression‐free survival after first recurrence (PFS‐R), overall survival after first recurrence (OS‐R) and recurrence frequency. The Kaplan–Meier analysis, univariate and multivariate Cox proportional hazard analysis, and the Prentice, Williams and Peterson counting process (PWP‐CP) model were adopted.ResultsThere were 70 patients included in the study, and recurrence occurred twice in more than 71% of patients, and 49.9% of patients relapsed ≥ three times. The recurrence pattern in over half of the patients at first recurrence was multifocal and distant disease, and abdominal or pelvic mass and liver metastasis were the most common. The 5‐year PFS‐R was 29.3%, and the 10‐year PFS‐R was 11.3%; the 5‐year OS‐R was 94.9%, and the 10‐year OS‐R was 87.9%. Kaplan–Meier analysis demonstrated that patients with distant recurrence and PFS1 (PFS when first recurrence occurred) ≤60 months had worse PFS‐R (p = 0.017, 0.018), and patients with PFS‐R ≤ 34 months had worse OS‐R (p = 0.023). It demonstrated that PFS1 ≤ 60 months (hazard ratio, HR 1.9, 95% confidence interval [CI]: 1.1–3.4, p = 0.028) was an independent risk factor for PFS‐R, and local lesion at recurrence (HR 0.488, 95% CI: 0.3–0.9, p = 0.027) was an independent protective factor for PFS‐R. In addition, it demonstrated that PFS‐R ≤ 33 months (HR 5.5, 95% CI: 1.2–25.3, p = 0.028) was an independent risk factor for OS‐R. The PWP‐CP analysis showed that laparoscopic operation (at each operation) could significantly increase recurrence times (p = 0.002, HR = 3.4), and no existence of gross residual lesion (R0) at each recurrence operation could significantly decrease recurrence frequency (p < 0.001, HR <0.001).ConclusionsThe recurrence pattern in patients with recurrent adult granulosa cell tumor was characterized as late and repeated, multifocal, and distant relapse. It has been demonstrated that PFS1 ≤ 60 months and distant lesion at recurrence are independent risk factors for PFS‐R, and PFS‐R ≤ 33 months is an independent risk factor for OS‐R. The PWP‐CP model showed that the transabdominal approach and surgery reaching R0 could significantly decrease the recurrence frequency.

Stage, treatment and survival of low‐grade serous ovarian carcinoma in the Netherlands: A nationwide study

AbstractIntroductionSerous ovarian carcinomas constitute the largest group of epithelial ovarian cancer (60%–75%) and are further classified into high‐ and low‐grade serous carcinoma. Low‐grade serous carcinoma (LGSC) is a relatively rare subtype (approximately 5% of serous carcinomas) and epidemiologic studies of large cohorts are scarce. With the present study we aimed to report trends in stage, primary treatment and relative survival of LGSC of the ovary in a large cohort of patients in an effort to identify opportunities to improve clinical practice and outcome of this relatively rare disease.Material and MethodsPatients diagnosed with LGSC between 2000 and 2019 were identified from the Netherlands Cancer Registry (n = 855). Trends in FIGO stages and primary treatment were analyzed with the Cochran–Armitage trend test, and differences in and trends of 5‐year relative survival were analyzed using multivariable Poisson regression.ResultsOver time, LGSC was increasingly diagnosed as stage III (39.9%–59.0%) and IV disease (5.7%–14.4%) and less often as stage I (34.6%–13.5%; p < 0.001). Primary debulking surgery was the most common strategy (76.2%), although interval debulking surgery was preferred more often over the years (10.6%–31.1%; p < 0.001). Following primary surgery, there was >1 cm residual disease in only 15/252 patients (6%), compared with 17/95 patients (17.9%) after interval surgery. Full cohort 5‐year survival was 61% and survival after primary debulking surgery was superior to the outcome following interval debulking surgery (60% vs 34%). Survival following primary debulking surgery without macroscopic residual disease (73%) was better compared with ≤1 cm (47%) and >1 cm residual disease (22%). Survival following interval debulking surgery without macroscopic residual disease (51%) was significantly higher than after >1 cm residual disease (24%). Except FIGO stage II (85%–92%), survival did not change significantly over time.ConclusionsOver the years, LGSC has been diagnosed as FIGO stage III and stage IV disease more often and interval debulking surgery has been increasingly preferred over primary debulking in these patients. Relative survival did not change over time (except for stage II) and worse survival outcomes after interval debulking surgery were observed. The results support the common recommendation to perform primary debulking surgery in patients eligible for primary surgery.

Pregnancy‐associated gynecological cancer in New South Wales, Australia 1994–2013: A population‐based historical cohort study

AbstractIntroductionPregnancy‐associated gynecological cancer (PAGC) refers to cancers of the ovary, uterus, fallopian tube, cervix, vagina, and vulva diagnosed during pregnancy or within 12 months postpartum. We aimed to describe the incidence of, and perinatal outcomes associated with, invasive pregnancy‐associated gynecological cancer.Material and methodsWe conducted a population‐based historical cohort study using linked data from New South Wales, Australia. We included all women who gave birth between 1994 and 2013, with a follow‐up period extending to September 30, 2018. Three groups were analyzed: a gestational PAGC group (women diagnosed during pregnancy), a postpartum PAGC group (women diagnosed within 1 year of giving birth), and a control group (women with control diagnosis during pregnancy or within 1 year of giving birth). We used generalized estimation equations to compare perinatal outcomes between study groups.ResultsThere were 1 786 137 deliveries during the study period; 70 women were diagnosed with gestational PAGC and 191 with postpartum PAGC. The incidence of PAGC was 14.6/100 000 deliveries and did not change during the study period. Women with gestational PAGC (adjusted odds ratio [aAOR] 6.81, 95% confidence interval [CI] 2.97–15.62) and with postpartum PAGC (aOR 2.65, 95% CI 1.25–5.61) had significantly increased odds of a severe maternal morbidity outcome compared with the control group. Babies born to women with gestational PAGC were more likely to be born preterm (aOR 3.11, 95% CI 1.47–6.59) and were at increased odds of severe neonatal complications (aOR 3.47, 95% CI 1.45–8.31) compared with babies born to women without PAC.ConclusionsThe incidence of PAGC has not increased over time perhaps reflecting, in part, the effectiveness of cervical screening and early impacts of human papillomavirus vaccination programs in Australia. The higher rate of preterm birth among the gestational PAGC group is associated with adverse outcomes in babies born to these women.

Negative margins and negative HPV tests after large loop excision of the transformation zone: A nationwide historical cohort study

Abstract Introduction Adequate treatment of cervical precancer, defined as negative margins and a negative HPV test post‐treatment, is essential for cervical cancer prevention, as inadequate excision of cervical precancer and a positive HPV test are associated with increased risk of recurrence. Here, we aimed to describe trends in the proportion of women receiving adequate treatment in Denmark. Material and Methods Nationwide historical cohort study including Danish women ≥18 years treated with large loop excision of the transformation zone (LLETZ) from 2013 to 2022. Using the Danish Pathology Register, we collected information on all LLETZ procedures performed due to cervical intraepithelial neoplasia grade 1 or worse (CIN1+). We calculated the proportion of negative margins and negative HPV tests post‐treatment, overall and stratified by histology, age, calendar time, and residing region. Results were mainly reported descriptively. Results We included 41 128 women (median age: 35 years, interquartile range: 28–44). A total of 20 744 (50.4%) had negative margins, with the lowest proportion in women with CIN3 (47.2%) or adenocarcinoma in situ (38.3%). The proportion of negative margins declined with increasing age, from 54.1% in women aged 18–29 years to 43.6% in women aged ≥50 years. Overall, 62.4% had a negative HPV test, with no major differences observed across histology groups. The proportion of negative HPV tests ranged from 62.8% to 66.9% in women aged 18–49, whereas it was lower in women aged ≥50 years (48.4%). Conclusions Women aged ≥50 years were less likely to have negative margins and a negative HPV test post‐treatment compared to women aged 18–49. These findings prompt a need to optimize treatment in this group of women to reduce the risk of cervical cancer.

Cervix cytology samples revealed increased methylation of the human markers FAM19A4/miR124‐2 up to 8 years before adenocarcinoma

AbstractIntroductionMethylation analysis of the promoter region of tumor‐suppressor genes has previously shown high sensitivity for detection of high‐grade cervical intraepithelial neoplasia (CIN) and cancer. HPV‐testing has a high sensitivity to identify women at risk to develop cancer, and has been implemented in cervical screening programs in several countries. But in most HPV‐positive women the infection will clear and they will not develop cancer. Testing for methylation could help to identify women who have potentially progressive cervical disease and need closer follow‐up. The goal of the present study was to investigate the potential use of methylation as a triage test of HPV‐positive women in the screening program.Material and methodsA collection of liquid‐based cytology (LBC) samples from 106 women, collected between 4 months and 8 years before histologically confirmed cervical cancer or CIN3, was analyzed for hypermethylation of the human genes FAM19A4 and miR124‐2.ResultsMethylation was detected in 45% (33/73) of normal LBC samples from women who later developed CIN3+, compared with 10% (3/31) of normal LBC samples from women without subsequent dysplasia (P = 0.0006). Overall, methylation was detected in 39% (14/36), 51% (19/37), 61% (14/23) and 70% (7/10) of LBC samples from women who later developed CIN3, adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), respectively. Positive methylation analysis was not significantly more frequent than abnormal cytology of atypical squamous cells of unclear significance or worse (ASCUS+) in LBC samples collected 4 months to 8 years before SCC or AIS; however, prior to the development of ADC, methylation was observed in 7/10 LBC samples, despite normal cytology. Overall, LBC samples collected before invasive cancer (ADC and SCC) were more frequently positive in the methylation analysis than in cytological analysis of ASCUS+ (P = 0.048). For LBC samples collected more than 2 years before the development of AIS, SCC or ADC, methylation analysis showed a higher positivity rate than cytology did.ConclusionsTesting for methylation of FAM19A4/miR124‐2 as a triage for HPV‐positive women would be useful to identify women at risk of cancer development, especially adenocarcinoma. Further studies are needed to estimate the cost‐effectiveness before introducing methylation testing in the screening program.

Cervical cancer in Region Skåne, Sweden 2017–2020 after the implementation of primary HPV screening: A quality assurance audit

AbstractIntroductionPrimary human papilloma virus (HPV) screening to detect cervical cancer and dysplastic lesions was implemented in Region Skåne 2017 for women aged 30–70. The aim of this study was to characterize the screening history of women diagnosed with cervical cancer to evaluate the performance of the screening program, as well as to assess the cancer treatments given and shortcomings in the follow‐up of women with cervical dysplasia.Material and methodsWe performed a quality assurance audit. The data was collected from the National Cervical Cancer Prevention Registry, Region Skåne Labmedicin database and the Melior Journal system in 2017–2020.ResultsWe identified 247 women diagnosed with invasive cervical cancer in Region Skåne in 2017–2020. Of these, 35 (14.2%) had a screening history over at least two screening rounds before diagnosis. There were 25 (10.1%) women diagnosed with cervical cancer in between screening intervals, i.e., interval cancer. The most common screening history in women with cervical cancer was irregular screening (143, 57.9%), followed by women being above screening age (44, 17.8%). HPV was detected in 96% of the cases, either in cervical cytology or in the tumor tissue. The screening program detected the disease in 96 (38.9%) of the patients, 149 (60.3%) were diagnosed through symptoms and two (0.80%) as a result of incidental findings.ConclusionsThe most powerful tool in the prevention of cervical cancer is screening program attendance. Prolongation with HPV screening among elderly women will also reduce the incidence of cervical cancer. Today, such cancers are usually discovered when symptoms appear.

Contraception and sterilization selection at delivery among pregnant patients with malignancy

AbstractIntroductionSince malignancy during pregnancy is uncommon, information regarding contraception selection or sterilization at delivery is limited. The objective of this study was to examine the type of long‐acting reversible contraception or surgical sterilization procedure chosen by pregnant patients with malignancy at delivery.Material and methodsThis cross‐sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample in the USA. The study population was vaginal and cesarean deliveries in a hospital setting from January 2017 to December 2020. Pregnant patients with breast cancer (n = 1605), leukemia (n = 1190), lymphoma (n = 1120), thyroid cancer (n = 715), cervical cancer (n = 425) and melanoma (n = 400) were compared with 14 265 319 pregnant patients without malignancy. The main outcome measures were utilization of long‐acting reversible contraception (subdermal implant or intrauterine device) and performance of permanent surgical sterilization (bilateral tubal ligation or bilateral salpingectomy) during the index hospital admission for delivery, assessed with a multinomial regression model controlling for clinical, pregnancy and delivery characteristics.ResultsWhen compared with pregnant patients without malignancy, pregnant patients with breast cancer were more likely to proceed with bilateral salpingectomy (adjusted odds ratio [aOR] 2.30) or intrauterine device (aOR 1.91); none received the subdermal implant. Pregnant patients with leukemia were more likely to choose a subdermal implant (aOR 2.22), whereas those with lymphoma were more likely to proceed with bilateral salpingectomy (aOR 1.93) and bilateral tubal ligation (aOR 1.76). Pregnant patients with thyroid cancer were more likely to proceed with bilateral tubal ligation (aOR 2.21) and none received the subdermal implant. No patients in the cervical cancer group selected long‐acting reversible contraception, and they were more likely to proceed with bilateral salpingectomy (aOR 2.08). None in the melanoma group chose long‐acting reversible contraception. Among pregnant patients aged <30, the odds of proceeding with bilateral salpingectomy were increased in patients with breast cancer (aOR 3.01), cervical cancer (aOR 2.26) or lymphoma (aOR 2.08). The odds of proceeding with bilateral tubal ligation in pregnant patients aged <30 with melanoma (aOR 5.36) was also increased.ConclusionsThe results of this nationwide assessment in the United States suggest that among pregnant patients with malignancy, the preferred contraceptive option or method of sterilization at time of hospital delivery differs by malignancy type.

High prevalence of HPV16 and high‐grade cytology in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

AbstractIntroductionMany countries have adopted active surveillance in women with cervical intraepithelial neoplasia grade 2 (CIN2), leaving the lesion untreated. However, there is a lack of consensus on the eligibility criteria for active surveillance across countries, with some abstaining from active surveillance in women with human papilloma virus 16 (HPV16) or a high‐grade cytology. Here, we aimed to describe the distribution of HPV genotypes, age, and cytology in women undergoing active surveillance for CIN2.Material and methodsWe conducted a single‐center cross‐sectional study on women aged 23–40 undergoing active surveillance for CIN2 during 2000–2010. Women were identified through the Danish Pathology Data Bank (DPDB) at Aarhus University Hospital, Denmark. We collected information on basic characteristics and results of histopathological examinations via DPDB. Women were deemed eligible for inclusion if they had a subsequent biopsy after index CIN2, and had no prior record of CIN2+, hysterectomy, or cone biopsy. Archived biopsies underwent HPV genotyping using the HPV SPF10‐ DEIA‐LiPA25 system, and the diagnosis was re‐evaluated by three expert pathologists. We used the Chi squared‐test (p‐value) for comparison across groups.ResultsWe identified 3623 women with CIN2 of whom 455 (12.6%) were included. Most women were 30 years or younger (73.8%), and half (48.8%) had a high‐grade index cytology. The prevalence of any high‐risk HPV was 87.0%, with HPV16 being the most prevalent genotype (35.6%). The prevalence of HPV16 was significantly higher in women aged 30 or younger (39.3%) compared to women older than 30 years (25.2%) (p = 0.006). Upon expert review, 261 (57.4%) had CIN2 confirmed, whereas 56 (12.3%) were upgraded to CIN3 and 121 (26.6%) were downgraded to CIN1/normal. While the HPV16 prevalence was similar between community and expert confirmed CIN2, the prevalence of HPV16 was significantly higher in women with expert CIN3 compared to women with expert CIN1/normal (64.3% vs. 19.0%, p = 0.001).ConclusionsThe high prevalence of HPV16 and high‐grade cytology imply that these women may be perceived as a high‐risk population and non‐eligible for active surveillance in countries outside Denmark. Future studies should investigate the importance of HPV, age, cytology, and expert review on risk of progression to help refine criteria for active surveillance.

Rationality of FIGO 2018 IIIC restaging of cervical cancer according to local tumor size: A cohort study

AbstractIntroductionFIGO 2018 IIIC remains controversial for the heterogeneity of its prognoses. To ensure a better management of cervical cancer patients in Stage IIIC, a revision of the FIGO IIIC version classification is required according to local tumor size.Material and methodsWe retrospectively enrolled cervical cancer patients of FIGO 2018 Stages I–IIIC who had undergone radical surgery or chemoradiotherapy. Based on the tumor factors from the Tumor Node Metastasis staging system, IIIC cases were divided into IIIC‐T1, IIIC‐T2a, IIIC‐T2b, and IIIC‐(T3a+T3b). Oncologcial outcomes of all stages were compared.ResultsA total of 63 926 cervical cancer cases were identified, among which 9452 fulfilled the inclusion criteria and were included in this study. Kaplan–Meier pairwise analysis showed that: the oncology outcomes of I and IIA were significantly better than of IIB, IIIA+IIIB, and IIIC; the oncology outcome of IIIC‐(T1‐T2b) was significantly better than of IIIA+IIIB and IIIC‐(T3a+T3b); no significant difference was noted between IIB and IIIC‐(T1‐T2b), or IIIC‐(T3a+T3b) and IIIA+IIIB. Multivariate analysis indicated that, compared with IIIC‐T1, Stages T2a, T2b, IIIA+IIIB and IIIC‐(T3a+T3b) were associated with a higher risk of death and recurrence/death. There was no significant difference in the risk of death or recurrence/death between patients with IIIC‐(T1‐T2b) and IIB. Also, compared with IIB, IIIC‐(T3a+T3b) was associated with a higher risk of death and recurrence/death. No significant differences in the risk of death and recurrence/death were noted between IIIC‐(T3a+T3b) and IIIA+IIIB.ConclusionsIn terms of oncology outcomes of the study, FIGO 2018 Stage IIIC of cervical cancer is unreasonable. Stages IIIC‐T1, T2a, and T2b may be integrated as IIC, and it might be unnecessary for T3a/T3b cases to be subdivided by lymph node status.

Assessing artificial intelligence enabled liquid‐based cytology for triaging HPV‐positive women: a population‐based cross‐sectional study

AbstractIntroductionCytology‐based triaging is commonly used to manage the care of women with positive human papillomavirus (HPV) results, but it suffers from subjectivity and a lack of sensitivity and reproducibility. The diagnostic performance of an artificial intelligence‐enabled liquid‐based cytology (AI‐LBC) triage approach remains unclear. Here, we compared the clinical performance of AI‐LBC, human cytologists and HPV16/18 genotyping at triaging HPV‐positive women.Material and methodsHPV‐positive women were triaged using AI‐LBC, human cytologists and HPV16/18 genotyping. Histologically confirmed cervical intraepithelial neoplasia grade 2/3 or higher (CIN2+/CIN3+) were accepted as thresholds for clinical performance assessments.ResultsOf the 3514 women included, 13.9% (n = 489) were HPV‐positive. The sensitivity of AI‐LBC was comparable to that of cytologists (86.49% vs 83.78%, P = 0.744) but substantially higher than HPV16/18 typing at detecting CIN2+ (86.49% vs 54.05%, P = 0.002). While the specificity of AI‐LBC was significantly lower than HPV16/18 typing (51.33% vs 87.17%, P < 0.001), it was significantly higher than cytologists at detecting CIN2+ (51.33% vs 40.93%, P < 0.001). AI‐LBC reduced referrals to colposcopy by approximately 10%, compared with cytologists (51.53% vs 60.94%, P = 0.003). Similar patterns were also observed for CIN3+.ConclusionsAI‐LBC has equivalent sensitivity and higher specificity compared with cytologists, with more efficient colposcopy referrals for HPV‐positive women. AI‐LBC could be particularly useful in regions where experienced cytologists are few in number. Further investigations are needed to determine triaging performance through prospective designs.

First step in implementation of opportunistic salpingectomy for prevention of ovarian cancer: Current care and its determinants

AbstractIntroductionOpportunistic salpingectomy (OS) refers to additional removal of the fallopian tubes during abdominal surgery performed for another medical indication, as prevention for ovarian cancer. As OS has been inconsistently implemented, its clinical practice varies worldwide. To reduce this variation, insight is required into current clinical practice and its determinants. Therefore, the study aim was to determine the implementation of counseling and performance of OS between 2015 and 2018, and its patient, surgical, physician, and hospital characteristics.Material and methodsRetrospective study using electronic medical records from six different Dutch hospitals: two academic, two large teaching, and two non‐teaching hospitals. Patients were considered eligible for OS if they underwent elective non‐obstetric abdominal surgery for a gynecological indication from January 2015 through December 2018. Primary outcomes were uptake of counseling and performance of OS. Multilevel multivariable logistic regression analyses were conducted to identify characteristics associated with OS.ResultsA total of 3214 patients underwent elective non‐obstetric abdominal surgery for a gynecological indication and were eligible for OS. Counseling on OS increased significantly from 2.9% in 2015 to 29.4% in 2018. In this period, 440 patients were counseled on OS, of which 95.9% chose OS. Performance of OS increased significantly from 6.9% in 2015 to 44.5% in 2018. Counseling for and performance of OS were more likely in patients who had surgery by laparoscopic approach, were counseled by a gynecological resident, or had more than three contact moments before surgery. Additionally, OS was less likely in patients who had vaginal surgery.ConclusionsAlthough the uptake of OS increased from 2015 to 2018, the majority of patients who were eligible for OS were not counseled and did not undergo OS. Its clinical practice varies on patient, surgery, and physician characteristics. Therefore, an implementation strategy tailored to associated determinants is recommended.

Long‐term risk of cancer among the first‐degree relatives of epithelial ovarian cancer patients: A cohort study with 48 years of follow up

AbstractIntroductionThe long‐term risk of cancer among first‐degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are well established, but these account for only about 15% of ovarian cancer cases. Less is known about the possible familial risks of sporadic ovarian cancers.Material and methodsUsing registry data, we conducted a retrospective cohort study with a total of 6501 first‐degree relatives of 559 epithelial ovarian cancer patients. We studied the occurrence of overall cancer and cancer in specific sites known or suspected to be associated with ovarian cancer (breast, cervix, colon, endometrium, lung and trachea, skin melanoma, ovary, pancreas, prostate, rectum, and stomach).ResultsThe overall number of cancers was not increased among the first‐degree relatives of epithelial ovarian cancer patients during the up to 48 years of follow up. Among female relatives, the standardized incidence ratio for ovarian cancer was 1.92 (95% CI 1.27–2.79), mostly explained by a 2.30‐fold (95% CI 1.46–3.45) risk among the patients' sisters. There was a decreasing trend in the standardized incidence ratio for ovarian cancer among patients' sisters by increasing age of the index patient.ConclusionsIn our study cohort, we did not observe an increase in the overall cancer risk among the first‐degree relatives of epithelial ovarian cancer patients in comparison with the general population. The risk for ovarian cancer, however, was increased. Current recommendations suggest prophylactic removal of the fallopian tubes and ovaries only with identified inherited risk factors. Our results emphasize the role of genetic counseling and testing, particularly in young ovarian cancer patients and their close female relatives.

Enlarged cardiophrenic lymph nodes predict disease involvement of the upper abdomen and the outcome of primary surgical debulking in advanced ovarian cancer

AbstractIntroductionThe outcome of ovarian cancer patients is highly dependent on the success of primary debulking surgery in terms of postoperative residual disease. This study critically evaluates the clinical impact of preoperative radiologic assessment of the cardiophrenic lymph node (CPLN) status in advanced ovarian cancer.Material and methodsBaseline CT scans of 178 stage III and IV ovarian cancer patients were retrospectively reviewed by two independent radiologists. CPLN enlargement defined at a short‐axis ≥5 mm was evaluated for its prognostic value and predictive power of upper abdominal tumor involvement and the chance of complete intra‐abdominal tumor resection at primary debulking surgery. Only patients without surgically removed CPLN were eligible for this study.ResultsEnlarged CPLNs were detected in 50% of patients and correlated with radiologically suspicious (P = .028) and histologically confirmed (P = .001) paraaortic lymph node metastases. CPLNs ≥ 5 mm were associated with high CA‐125 levels at baseline and revealed independent prognostic relevance for progression‐free survival (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.33‐3.42) and overall survival (HR 2.18, 95% CI 1.16‐4.08). Noteworthy, patients with enlarged CPLNs nonetheless benefit from complete intra‐abdominal tumor debulking in terms of an improvement in progression‐free survival (HR 0.60, 95% CI 0.38‐0.94) and overall survival (HR 0.59, 95% CI 0.35‐0.82). Enlarged CPLNs correctly predicted carcinomatosis of the upper abdomen in 94.6%. A predictive score of complete tumor debulking, termed CD‐score, which integrates, beside a CPLN short axis <5 mm, an ascites volume <500 mL, and CA‐125 levels <500 U/mL at baseline, correctly predicted complete intra‐abdominal debulking in 100% of patients.ConclusionsCPLNs ≥5 mm predict upper abdominal tumor involvement. The application of the CD‐score predicted complete macroscopic tumor resection at primary surgery in all of the patients. Although, CPLN pathology suggests extra‐abdominal disease, we consistently demonstrated that patients nonetheless benefit from complete intra‐abdominal tumor resection.

Venous thromboembolism in women with ovarian cancer undergoing neoadjuvant chemotherapy prior to cytoreductive surgery: A retrospective study

AbstractIntroductionOvarian cancer is associated with a venous thromboembolism risk of at least 7.2% by 2 years from diagnosis, and although patients undergoing surgery benefit from routine thromboprophylaxis, those undergoing neoadjuvant chemotherapy do not. This study aims to determine the venous thromboembolism incidence in patients with ovarian cancer undergoing neoadjuvant chemotherapy, and explore whether any subset is at higher risk, in order to evaluate whether thromboprophylaxis is justified in some or all of these patients.Material and methodsThis was a retrospective review of all women undergoing neoadjuvant chemotherapy for FIGO radiological stages III and IV primary ovarian, fallopian tube, and primary peritoneal cancer, between 2000 and 2015, in a London tertiary cancer center. The primary outcome was venous thromboembolism rate among women undergoing neoadjuvant chemotherapy. The secondary outcomes were patient or treatment factors associated with venous thromboembolism risk, including age, body mass index, smoking status, performance status, and tumor stage.ResultsWe identified 278 eligible women from the ovarian cancer database. Fifty‐eight women (20.9%) developed venous thromboembolism between initial presentation and the immediate postoperative period, of which 45 (77.6%) developed a pulmonary embolism. In all, 15.1% of women developed venous thromboembolism from the start of neoadjuvant chemotherapy. Age, body mass index, smoking, or other comorbidities were not significantly associated with venous thromboembolism risk. One woman died from massive pulmonary embolism, 27 women underwent inferior vena cava filter insertion, and 10 had surgery delayed.ConclusionsThis study demonstrates an unacceptably high rate of avoidable venous thromboembolism including pulmonary embolism in these women, which complicates and delays treatment. Thromboprophylaxis during neoadjuvant chemotherapy should now be assessed prospectively.

AI‐driven simplification of surgical reports in gynecologic oncology: A potential tool for patient education

AbstractIntroductionThe emergence of large language models heralds a new chapter in natural language processing, with immense potential for improving medical care and especially medical oncology. One recent and publicly available example is Generative Pretraining Transformer 4 (GPT‐4). Our objective was to evaluate its ability to rephrase original surgical reports into simplified versions that are more comprehensible to patients. Specifically, we aimed to investigate and discuss the potential, limitations, and associated risks of using these simplified reports for patient education and information in gynecologic oncology.Material and MethodsWe tasked GPT‐4 with generating simplified versions from n = 20 original gynecologic surgical reports. Patients were provided with both their original report and the corresponding simplified version generated by GPT‐4. Alongside these reports, patients received questionnaires designed to facilitate a comparative assessment between the original and simplified surgical reports. Furthermore, clinical experts evaluated the artificial intelligence (AI)‐generated reports with regard to their accuracy and clinical quality.ResultsThe simplified surgical reports generated by GPT‐4 significantly improved our patients' understanding, particularly with regard to the surgical procedure, its outcome, and potential risks. However, despite the reports being more accessible and relevant, clinical experts highlighted concerns about their lack of medical precision.ConclusionsAdvanced language models like GPT‐4 can transform unedited surgical reports to improve clarity about the procedure and its outcomes. It offers considerable promise for enhancing patient education. However, concerns about medical precision underscore the need for rigorous oversight to safely integrate AI into patient education. Over the medium term, AI‐generated, simplified versions of these reports—and other medical records—could be effortlessly integrated into standard automated postoperative care and digital discharge systems.

Procedural sedation and analgesia versus general anesthesia for hysteroscopic myomectomy: A cost‐effectiveness analysis alongside a randomized controlled trial

Abstract Introduction Hysteroscopic myomectomy is the first‐choice treatment for symptomatic type 0 and 1 fibroids and was traditionally performed under general anesthesia. Over the last decade, surgical procedures have increasingly been performed in an outpatient setting under procedural sedation and analgesia. However, studies evaluating the safety and cost‐effectiveness of hysteroscopic myomectomy under procedural sedation and analgesia are lacking. This study aimed to assess the cost‐effectiveness of procedural sedation and analgesia with propofol in an outpatient setting for hysteroscopic myomectomy compared to general anesthesia in an operating room. Material and Methods This was a cost‐effectiveness analysis from a societal perspective alongside a multicenter randomized controlled non‐inferiority trial. It was conducted in 14 Dutch university and teaching hospitals. Women aged ≥18 years with symptomatic type 0/1 fibroids (maximum number 3, maximum diameter 3.5 cm), sufficient knowledge of Dutch/English, and American Society of Anesthesiologists class 1/2 were included. A total of 209 women were randomized to hysteroscopic myomectomy with procedural sedation and analgesia in an outpatient setting ( n  = 106) or general anesthesia in an operating room ( n  = 103). The primary outcome of the clinical trial was the percentage of complete resections measured by transvaginal ultrasonography 6 weeks postoperatively (non‐inferiority margin 7.5% of incomplete resections). Societal costs and quality‐adjusted life years (QALYs) were assessed. Societal costs were related to the percentage of complete resections and QALYs. Incremental Cost‐Effectiveness Ratios (ICERs) were calculated. Uncertainty surrounding these was estimated using bootstrapping. Follow‐up period was 12 months. Dutch Trial Register NTR 5357. Results Hysteroscopic resection was complete in 86/98 women (87.8%) with procedural sedation and analgesia and 79/89 women (88.8%) with general anesthesia, mean difference −0.0052 (95% CI −0.097 to 0.086). Non‐inferiority could not be demonstrated. There was a statistically significant difference in costs between procedural sedation and analgesia and general anesthesia (€−2577, 95% CI −3950 to −1157), but not in QALYs (0.011, 95% CI −0.019 to 0.040). The ICER per additional complete resection was €498 797 and for QALYs the ICER showed that procedural sedation and analgesia was dominant over general anesthesia. Conclusions In this study, procedural sedation and analgesia for hysteroscopic myomectomy in an outpatient setting is cost‐effective compared to general anesthesia in an operating room, although non‐inferiority for complete resections could not be demonstrated. We therefore suggest the outpatient use of procedural sedation and analgesia for hysteroscopic myomectomy.

Time trends in the clinical management of cervical intraepithelial neoplasia grade 2: A Danish register‐based study

AbstractIntroductionActive surveillance for cervical intraepithelial neoplasia grade 2 (CIN2) has been implemented recently in many countries, including the Nordic countries. In Denmark, the only eligibility criterion for active surveillance for CIN2 is that the woman should be of reproductive age. With this study, we aimed to evaluate clinical and socioeconomic characteristics in women with CIN2 managed by active surveillance or large loop excision of the transformation zone (LLETZ) and to evaluate temporal changes in the clinical management of CIN2.Material and MethodsWe conducted a Danish nationwide study using data from healthcare registries. All female residents aged 18–40 years, diagnosed with incident CIN2 from January 1, 1998, to February 29, 2020, were included. We collected data on age, index cytology result, year of CIN2 diagnosis, region of residence, civil status, HPV vaccination status, and socioeconomic position indicators. The variables were tabulated overall and by management group (active surveillance vs. LLETZ). To evaluate time trends, we used joinpoint regression to calculate the annual percentage change (APC), including 95% confidence intervals (CI).ResultsOf the 27 536 women with CIN2 included, 12 500 (45.4%) underwent active surveillance, and 15 036 (54.6%) underwent a LLETZ. Women undergoing active surveillance were younger, more often HPV‐vaccinated, and more likely to have a normal/low‐grade index cytology result than women undergoing LLETZ. Socioeconomic position indicators did not differ. Over time, the proportion of women undergoing active surveillance increased from 21.7% in 2004 to 73.6% in 2019 (APC 9.7, 95% CI 8.1–11.4). The proportion of women undergoing active surveillance aged <30 declined over time (APC −2.2, 95% CI −2.9 to −1.5). The proportion of women with normal/low‐grade index cytology increased slightly to 51.6% in 2019 (APC 0.8, 95% CI 0.4–1.3).ConclusionsThe use of active surveillance for CIN2 has increased over the past two decades in Denmark. Observed differences in characteristics between women undergoing active surveillance vs LLETZ are likely related to indications for clinical management.

Reproducibility of colposcopy quality indicators—A survey among members of the European Federation for Colposcopy

AbstractIntroductionColposcopy is an important part of the diagnostic work‐up of women with an abnormal cervical screening test as it is used to guide the collection of biopsies. Although quality assurance has been used in the evaluation of screening programs, not much is known about quality indicators for the diagnostics and treatment of screen‐positive women. Therefore, the European Federation for Colposcopy developed quality indicators aiming to support colposcopy practice across Europe. We performed a survey of colposcopy cases to determine if the quality indicators are understandable, relevant, and reproducible.Material and MethodsWe conducted a survey among all members of the European Federation for Colposcopy Quality and Standards Group from November 2022 to March 2023. Members were asked to collect information on a total of 17 quality indicators for 50 women who had been newly referred for colposcopy due to an abnormal screening test between January 1, 2020 to December 31, 2021. Results were reported descriptively.ResultsWe included data on 609 cases from 12 members across Europe. The majority of the quality indicators were either achieved or within reach of the agreed standard, often due to few countries with outlying data. One quality indicator had very low performance, although stratified results indicated that two countries had different clinical management of the patient type thereby skewing the results. In addition, discrepancies between the number of cases included in each quality indicator raised concerns regarding potential misunderstanding of the quality indicator and its objective.ConclusionsQuality indicators on colposcopy must be understandable to those collecting data, highlighting the importance of validating quality indicators before data collection.

Imaging features, clinical characteristics and neonatal outcomes of pregnancy luteoma: A case series and literature review

AbstractIntroductionThis study aimed to investigate the imaging features, clinical characteristics and neonatal outcomes of pregnancy luteoma.Material and methodsWe retrospectively analyzed patients with pregnancy luteoma admitted to the First Affiliated Hospital of Sun Yat‐sen University between January 2003 and December 2022. We recorded their imaging features, clinical characteristics and neonatal outcomes. Additionally, we reviewed relevant studies in the field.ResultsIn total, 127 cases were identified, including eight from our hospital and 119 from the literature. Most patients (93/127, 73.23%) were of reproductive age, 20–40 years old, and 66% were parous. Maternal hirsutism or virilization (such as deepening voice, acne, facial hair growth and clitoromegaly) was observed in 29.92% (38/127), whereas 59.06% of patients (75/127) were asymptomatic. Abdominal pain was reported in 13 patients due to compression, torsion or combined ectopic pregnancy. The pregnancy luteomas, primarily discovered during the third trimester (79/106, 74.53%), varied in size ranging from 10 mm to 20 cm in diameter. Seventy‐five cases were incidentally detected during cesarean section or postpartum tubal ligation, and 39 were identified through imaging or physical examination during pregnancy. Approximately 26.61% of patients had bilateral lesions. The majority of pregnancy luteomas were solid and well‐defined (94/107, 87.85%), with 43.06% (31/72) displaying multiple solid and well‐circumscribed nodules. Elevated serum androgen levels (reaching values between 1.24 and 1529 times greater than normal values for term gestation) were observed in patients with hirsutism or virilization, with a larger lesion diameter (P < 0.001) and a higher prevalence of bilateral lesions (P < 0.001). Among the female infants born to masculinized mothers, 68.18% (15/22) were virilized. Information of imaging features was complete in 22 cases. Ultrasonography revealed well‐demarcated hypoechoic solid masses with rich blood supply in 12 of 19 cases (63.16%). Nine patients underwent magnetic resonance imaging (MRI) or computed tomography (CT), and six exhibited solid masses, including three with multi‐nodular solid masses.ConclusionsPregnancy luteomas mainly manifest as well‐defined, hypoechoic and hypervascular solid masses. MRI and CT are superior to ultrasonography in displaying the imaging features of multiple nodules. Maternal masculinization and solid masses with multiple nodules on imaging may help diagnose this rare disease.

Procalcitonin and C‐reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS)

AbstractIntroductionSerum levels of procalcitonin and C‐reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers.Material and methodsThis prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1–6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated.ResultsAnastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity).ConclusionsProcalcitonin and C‐reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

Vulvar and vaginal cancer during pregnancy: A pooled analysis of 15 cases from the International Network on Cancer, Infertility and Pregnancy and review of the literature

Abstract Introduction Vulvovaginal cancer in pregnancy is rare. Limited data complicate decision‐making and patient counseling. Our review, coupled with new case data, fills a current gap in the literature and provides practical insights. Material and Methods Oncological and obstetric data of these pregnancies were examined by a case collection from the International Network on Cancer, Infertility and Pregnancy (INCIP) registry (vulvar n  = 10, vaginal n  = 5) and a literature review (vulvar n  = 46, vaginal n  = 37). Results Although preoperative imaging of inguinofemoral lymph nodes is feasible, only 16.1% of vulvar cancer patients underwent ultrasound or MRI. Treatment was initiated during pregnancy for 69.1% of vulvar cancer and 28.4% of vaginal cancer patients. Surgical lymph node staging of vulvar cancer was postponed until after delivery in 10 cases, although uni‐ or bilateral lymphadenectomy during pregnancy was not associated with more complications. Delivery outcomes included a live birth rate of 96.4% for vulvar cancer and 50% for vaginal cancer due to the high rate of pregnancy terminations, with most births preterm. The overall 5‐year survival rates for vulvar (81.3%) and vaginal (66.4%) cancer during pregnancy are comparable to nonpregnant populations, indicating that pregnancy does not adversely impact maternal prognosis. Conclusions This study underscores the feasibility of adapting standard oncological care for pregnant patients, emphasizing multidisciplinary teams to optimize maternal and fetal outcomes.

Carboplatin plus paclitaxel weekly dose‐dense chemotherapy for high‐grade ovarian cancer: A re‐evaluation

AbstractIntroductionWe compared oncologic and clinical outcomes in patients with advanced ovarian cancer who received dose‐dense weekly paclitaxel with 3‐weekly carboplatin with those who received standard 3‐weekly chemotherapy.Material and methodsComparison of all consecutive patients with advanced (International Federation of Gynecology and Obstetrics stages III‐IV) ovarian cancer who received a dose‐dense protocol between 2010 and 2016 with an immediate historical cohort of consecutive patients who received standard chemotherapy. Patients who received less than three cycles of treatment were excluded.ResultsIn all, 246 patients were included in the study, of whom 128 received the dose‐dense protocol and 118 were treated with the standard Q3‐week protocol. Patients in the dose‐dense group had significantly better progression‐free survival than those receiving the standard protocol (median progression‐free survival 22 vs 15 months; log rank = 0.026). The overall survival of patients in the dose‐dense group was also better than that of the patients in the standard protocol group; however, this difference was not statistically significant (median overall survival 66 vs 54 months; log rank = 0.185). The dose‐dense protocol remained significantly associated with favorable survival outcome in multivariable analysis adjusted for stage, histologic type, cytoreductive results and neoadjuvant chemotherapy. The use of the dose‐dense protocol was associated with higher rates of gastrointestinal, dermatologic, neurologic and hematologic side effects.ConclusionDespite the limitations associated with the comparison to a historical cohort, a dose‐dense chemotherapy protocol resulted in a significantly improved progression‐free survival and the overall survival tended to be better, but this difference did not reach statistical significance compared with the standard chemotherapy protocol, and may be considered as a treatment alternative, albeit with some increased side effects.

Frozen section diagnosis of borderline ovarian tumors with suspicious features of invasive cancer is a devil’s dilemma for the surgeon: A systematic review and meta‐analysis

AbstractIntroductionFrozen section diagnoses of borderline ovarian tumors are not always straightforward and a borderline frozen section diagnosis with suspicious features of invasive carcinoma (reported as “at least borderline” or synonymous descriptions) presents us with the dilemma of whether or not to perform a full surgical staging procedure. By performing a systematic review and meta‐analysis, the prevalence of straightforward borderline and “at least borderline” frozen section diagnoses, as well as proportion of patients with a final diagnosis of invasive carcinoma in these cases, were assessed and compared, as quantification of this dilemma may help us with the issue of this clinical decision.Material and methodsPubMed, EMBASE and Cochrane library databases were searched and studies discussing “at least borderline” frozen section diagnoses were included in the review. Numbers of specific frozen section diagnoses and subsequent final histological diagnoses were extracted and pooled analysis was performed to compare the proportion of patients diagnosed with invasive carcinoma following borderline and “at least borderline” frozen section diagnoses, presented as risk ratio and risk difference with 95% confidence intervals (95% CI).ResultsOf 4940 screened records, eight studies were considered eligible for quantitative analysis. A total of 921 women was identified and 230 (25.0%) of these women were diagnosed with “at least borderline” ovarian tumor at the time of frozen section. Final histological diagnoses were reported in five studies, including 61 women with an “at least borderline” diagnosis and 290 women with a straightforward borderline frozen section diagnosis. Twenty‐five of 61 women (41.0%) of the “at least borderline” group had invasive cancer at final diagnosis, compared with 28 of 290 women (9.7%) of the straightforward borderline frozen section group (risk difference −0.34, 95% CI −0.53 to −0.15; relative risk 0.25, 95% CI 0.13–0.50).ConclusionsWomen diagnosed with “at least borderline” frozen section diagnoses were found to have a higher chance of carcinoma upon final diagnosis when compared with women with a straightforward borderline frozen section diagnosis (41.0% vs 9.7%). Especially in the serous subtype, and after preoperative consent, full staging during initial surgery might be considered in these cases to prevent a second surgical procedure.

CA‐125 reduction during neoadjuvant chemotherapy is associated with success of cytoreductive surgery and outcome of patients with advanced high‐grade ovarian cancer

AbstractIntroductionThe objective was to assess whether an early response to neoadjuvant chemotherapy in women with advanced ovarian cancer may predict short‐ and long‐term clinical outcome.Material and methodsThis is a retrospective study of all women with stage III‐IV tubo‐ovarian cancer treated with neoadjuvant chemotherapy at a single center in Montreal between 2003 and 2014. Logistic regression models were used to evaluate the association between cancer antigen 125 (CA‐125) levels during neoadjuvant chemotherapy and debulking success. Cox proportional hazard models were used to estimate hazard ratios and their respective 95% CI for death and recurrence. Harrell's concordance indices were calculated to evaluate which variables best predicted the chemotherapy‐free interval and overall survival in our population.ResultsIn all, 105 women were included. Following the first, second, and third cycles of neoadjuvant chemotherapy, CA‐125 levels had a median reduction of 43.2%, 85.4%, and 92.9%, respectively, compared with CA‐125 levels at diagnosis. As early as the second cycle, CA‐125 was associated with overall survival (hazard ratio 1.03, 95% CI 1.01‐1.05, per 50 U/mL increment). By the third cycle, CA‐125 did not only predict overall survival (hazard ratio 1.04, 95% CI 1.01‐1.08), but it predicted overall survival better than the success of debulking surgery (Harrell's concordance index 0.646 vs 0.616). Both absolute CA‐125 levels and relative reduction in CA‐125 levels after 2 and 3 cycles predicted the chance to achieve complete debulking (P < .05).ConclusionsReduction of CA‐125 levels during neoadjuvant chemotherapy provides an early predictive tool that strongly correlates with successful cytoreductive surgery and long‐term clinical outcome in women with advanced high‐grade serous and endometrioid ovarian cancer.

Preoperative PET/CT score can predict incomplete resection after debulking surgery for advanced serous ovarian cancer better than CT score, MTV, tumor markers and hematological markers

AbstractIntroductionComplete resection after debulking surgery is strongly associated with prolonged survival for advanced serous ovarian cancer (ASOC). Though positron emission tomography/computed tomography (PET/CT) is more advantageous than computed tomorgraphy (CT) for detecting metastases, studies on the PET/CT prediction model for incomplete resection for ovarian cancer are insufficient. We analyzed and compared the predictive value of preoperative PET/CT score, CT score, metabolic parameters, tumor markers and hematological markers for incomplete resection after debulking surgery for ASOC.Material and methodsA total of 62 ASOC patients who underwent preoperative [18F]FDG PET/CT and debulking surgery were retrospectively analyzed. PET/CT and CT scores were based on the Suidan model. The predictive value of PET/CT score, CT score, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), human epididymis protein 4 (HE4), cancer antigen 125 (CA125), lymphocyte‐to‐monocyte ratio (LMR), platelet‐to‐lymphocyte ratio (PLR) and neutrophil‐to‐lymphocyte ratio (NLR) for incomplete resection were analyzed and compared.ResultsPreoperative PET/CT score had the highest predictive value for incomplete resection in primary debulking surgery group (sensitivity: 65.0%, specificity: 88.9%, area under the ROC curve (AUC): 0.847, p < 0.001), however, in secondary debulking surgery group, preoperative PET/CT score and CT score had the same and highest predictive value for incomplete resection (sensitivity: 80.0%, specificity: 94.7%, AUC: 0.853, p = 0.017), compared with preoperative metabolic parameters SUVmax and MTV, tumor markers HE4 and CA125, and hematological markers LMR, PLR and NLR. Preoperative PET/CT score ≥ 3 (Suidan model) and preoperative PET/CT score ≥ 2 predicted a high risk of incomplete resection after primary and secondary debulking surgeries, respectively. There was no statistical difference between primary and secondary debulking surgery groups in predictive value of PET/CT score for incomplete resection (p = 0.971). There were significant differences between PET/CT scores and CT scores in primary debulking surgery group and no significant differences in secondary debulking surgery group.ConclusionsA high PET/CT score predicted a high risk of incomplete resection. The preoperative PET/CT score had an identical predictive value in primary and secondary debulking surgery groups. PET/CT score was more accurate in the detection of metastases than CT score was.

Integrated bioinformatic analysis of dysregulated microRNA‐mRNA co‐expression network in ovarian endometriosis

AbstractIntroductionOvarian endometriosis is a frequently occurring gynecological disease with large socioeconomic impact. Accumulating evidence has suggested that aberrant miRNA‐mRNA interactions are involved in the pathogenesis and progression of ovarian endometriosis. This study aims to identify key miRNAs in ovarian endometriosis by using integrated bioinformatic analysis of a dysregulated miRNA‐mRNA co‐expression network.Material and methodsExpression profiling of miRNA and mRNA in three normal endometria and five pairs of ectopic/eutopic endometria from patients with ovarian endometriosis was determined by high‐throughput sequencing techniques. The data were then integrated with the public sequencing datasets (GSE105764 and GSE105765) using a non‐biased approach and a miRNA‐mRNA co‐expression regulatory network was constructed by in‐depth bioinformatic analysis.ResultsThe constructed miRNA‐mRNA network included 87 functionally DEMs, 482 target mRNAs and 1850 paired miRNA‐mRNA regulatory interactions. Specifically, five miRNAs (miR‐141‐3p, miR‐363‐3p, miR‐577, miR‐767‐5p, miR‐96‐5p) were gradually decreased and two miRNAs (miR‐493‐5p, miR‐592) were gradually increased from normal endometria to eutopic endometria, and then ectopic endometria tissues. Importantly, miR‐141‐3p, miR‐363‐3p and miR‐96‐5p belonged to the miR‐200 family, miR‐106a‐363 cluster and miR‐183/96/182 cluster, respectively. Their target mRNAs were mainly associated with cell adhesion, locomotion and binding, which are suggested to play vital regulatory roles in the pathogenesis of ovarian endometriosis.ConclusionsIntegrated bioinformatic analysis of the miRNA‐mRNA co‐expression network defines the crucial roles of the miR‐200 family, miR‐106a‐363 cluster and miR‐183/96/182 cluster in the pathogenesis of ovarian endometriosis. Further in‐depth functional studies are needed to unveil the molecular mechanisms of these miRNAs, and may provide clues for the optimization of therapeutic strategies for ovarian endometriosis.

Investigating the effect of optimal cytoreduction in the context of platinum sensitivity in high‐grade serous ovarian cancer

AbstractIntroductionThe survival benefits of surgical cytoreduction in ovarian cancer are well‐established. However, the surgical outcome has never been assessed while controlling for the efficacy of chemotherapy. This leaves the possibility that cytoreduction may not be beneficial for patients whose cancer does not respond well to adjuvant treatment. We sought to answer whether surgical cytoreduction independently improves overall survival when controlling for chemotherapy outcome.Material and MethodsWe performed a retrospective case–control study using our institution's ovarian cancer database to evaluate the effect of optimal cytoreduction on advanced stage, high‐grade serous ovarian cancer. Patients' characteristics were compared using both univariate and multivariate regression modeling to assess for independent predictors of overall survival.ResultsA total of 470 patients were assessed for inclusion; 234 responders to chemotherapy and 98 nonresponders. Significant survival characteristics were identified and included in the multivariate analysis. Independent predictors of survival in the multivariate analysis were age, responder status, optimal cytoreduction, neoadjuvant chemotherapy, and number of chemotherapy cycles. Kaplan–Meier survival curves showed improved survival for both patients who responded to chemotherapy and for those undergoing optimal cytoreduction (p < 0.001). We also demonstrated improved survival for patients receiving optimal cytoreduction among both nonresponders and responders (p < 0.001).ConclusionsOur analysis shows that patients who undergo optimal cytoreduction have an overall survival benefit regardless of their response to chemotherapy. Therefore, cytoreduction should be considered in all patients, even in those with advanced disease, if an optimal result can be achieved. This study was underpowered to assess patients who received neoadjuvant chemotherapy as a separate subgroup, but the order of treatment was controlled for in the overall analysis.

Residual tumor and primary debulking surgery vs interval debulking surgery in stage IV epithelial ovarian cancer

AbstractIntroductionIt is debated whether women with FIGO (International Federation of Gynecology and Obstetrics) Stage IV epithelial ovarian cancer should be offered primary debulking surgery (PDS) or interval debulking surgery (IDS). Furthermore, the impact of complete resection of intra‐abdominal disease (R0) despite their extra‐abdominal metastases is questioned. The objective of this study was to investigate the impact of intra‐abdominal residual tumor, Stage IVA vs IVB, the localization and number of metastases defining Stage IV disease on overall survival (OS) comparing PDS and IDS in FIGO Stage IV epithelial ovarian cancer.Material and MethodsWe included 2091 women registered with Stage IIIC–IV ovarian cancer in the Danish Gynecological Cancer Database during 2009–2016. The impact of residual tumor was evaluated using univariate and multivariate analyses.ResultsIn total, 681 patients had stage IV disease, of whom 26% underwent PDS, 38% IDS, and 36% chemotherapy only. Overall survival for PDS and IDS were similar. Patients achieving R0 at PDS showed a tendency towards a higher OS than patients achieving R0 at IDS, though the difference was non‐significant. In women with Stage IVA and IVB disease there was a survival benefit in achieving R0 both when treated with PDS and IDS. Women with Stage IVB disease treated with chemotherapy only had a significantly lower OS than patients achieving R0 at both PDS and IDS. Malignant pleural effusion and having five metastatic sites compared with having one was associated with a poorer OS.ConclusionsOur study shows similar OS in patients with Stage IV disease treated with IDS compared with PDS. Complete intra‐abdominal tumor resection improves the prognosis in both PDS and IDS in Stage IV ovarian cancer. Malignant pleural effusion seems to be a negative prognostic factor and should have more focus in future studies.

Lack of consensus in calculation of interval cancer rates for cervical cancer screening

AbstractIntroductionIn 2018, nondisclosure of results of retrospective audits of cytology in interval cancers precipitated a crisis in the Irish national cervical screening programme. In response, an Expert Reference Group was convened which recommended a collaborative approach to the development of a new key performance indicator, the interval cancer rate. The Expert Reference Group also recommended that the Irish programme should collaborate with international colleagues to reach consensus on (i) the definition of an interval cervical cancer, (ii) the methodology to calculate the interval cancer rate, and (iii) benchmarking with other international programs. This study was undertaken to determine if a consensus regarding the definition of an interval cervical cancer and the calculation of an interval cancer rate exists.Material and MethodsA web‐based questionnaire was sent to 18 population‐based cervical screening programs. Inclusion criteria involved (1) a national or regional population‐based cervical screening prograe; (2) a country or region with a population ≥population of Ireland; (3) programs located in Europe, Australia, or Canada; (4) programs that had responded to a previously published international survey on the disclosure of retrospective cytology reviews in cervical cancer cases.ResultsThe response rate was nine out of 18. Of nine respondents, six had an agreed definition of interval cervical cancer, and four of these calculated an interval cancer rate. Three programs neither calculated interval cancer rates nor had any guidelines related to this. Of the six with an agreed definition, all respondents defined the numerator as invasive cancers in the screening age group, with four including microinvasive disease. Respondents included cancers diagnosed 3–5 years after the last screening test had been taken. Three respondents also included cancers diagnosed in women up to 3.5 years after they exited the screening program. Countries use different denominators, including (i) per women years, (ii) per number of screens, and (iii) per total cancers in screened population.ConclusionsThere is variation in the parameters used in interval cancer rate calculation. To allow benchmarking of cervical screening program performance, there is a need for consensus on a standardized method of interval cancer definition and interval cancer rate calculation.

Primary HPV screening for cervical cancer: Results after two screening rounds in a regional screening program in Finland

AbstractIntroductionSince 2012, cervical cancer screening has been conducted with a primary high‐risk human papillomavirus (hrHPV) test and conventional cytology triage in the city of Tampere, Finland. The women who were screened with the hrHPV test in 2012 were invited to participate in the second screening round in 2017. The aim of the present report was to compare the number of colposcopy referrals and the number of histological high‐grade squamous intraepithelial lesion (HSIL)+ (cervical intraepithelial neoplasia [CIN2+]) lesions between the first and second screening rounds of women of a specific age group who were screened twice with the hrHPV test.Material and methodsThe primary hrHPV test used was the RealTime hrHPV PCR assay by Abbott. Women with a positive hrHPV test and cytology triage equal to or worse than low‐grade squamous intraepithelial lesion or atypical glandular cells, favor neoplasia, were directly referred to colposcopy, whereas hrHPV‐positive women with a negative or equivocal cytology triage were re‐screened after approximately 12‐16 months. hrHPV‐negative women were scheduled for re‐screening after 5 years. The present report focuses on the cohort of women who were screened twice with the hrHPV test, who were 35‐55 years old in 2012, and 40‐60 years old in 2017.ResultsIn all, 8076 women were invited for HPV screening in 2012 and 8331 women were invited for the second round 5 years later, with attendance rates of 70% and 71%, respectively. Of the women who were screened in 2012, 4571 (69%) belonged to the 35‐ to 55‐year age cohort. In 2017, 4807 (73%) of the women aged 40‐60 years participated in the screening. In this cohort, 185 (4.0%) colposcopies were performed in the first screening round, compared with 139 (2.9%) in the second round, and the colposcopy rate was 29% smaller in the second round (P = .002). The number of histological HSIL+ cases was 38 (0.8%) during the first screening round and 29 (0.6%) during the second round (P = .220).ConclusionsIn the setting of routine organized cervical cancer screening, the initially high colposcopy rate associated with primary HPV screening seems to level off at the second screening round in women who were screened twice with an hrHPV test.

Preferences for follow up in long‐term survivors after cervical cancer

AbstractIntroductionAn increasing number of cervical cancer survivors combined with lack of data on the efficacy of long‐term surveillance, challenges existing follow‐up models. However, before introducing new follow‐up models, cervical cancer survivors’ own views on follow up are important. We aimed to explore preferences for follow up in long‐term cervical cancer survivors and their associations with self‐reported late‐effects.Material and methodsIn 2013, we mailed 974 Norwegian long‐term cervical cancer survivors treated during 2000‐2007 a questionnaire with items covering preferences for follow up after treatment, clinical variables and validated questionnaires covering anxiety, neuroticism and depression.ResultsWe included 471 cervical cancer survivors (response rate 57%) with a median follow up of 11 years. In all, 77% had FIGO stage I disease, and 35% were attending a follow‐up program at the time of survey. Of the patients, 55% preferred more than 5 years of follow up. This was also preferred by 57% of cervical cancer survivors who were treated with conization only. In multivariable analyses, chemo‐radiotherapy or surgery with radiation and/or chemotherapy (heavy treatment) and younger age were significantly associated with a preference for more than 5 years’ follow up. Late effects were reported by more than 70% of the cervical cancer survivors who had undergone heavy treatment.ConclusionsOur study reveals the need for targeted patient education about the benefits and limitations of follow up. To meet increasing costs of cancer care, individualized follow‐up procedures adjusted to risk of recurrence and late‐effects in cervical cancer survivors are warranted.

Atypical glandular lesions of the cervix and risk of cervical cancer

AbstractIntroductionCytology screening has been effective in reducing risks for cervical squamous cell carcinoma but less so for adenocarcinoma. We explored the association of atypical glandular cells or absence of glandular cells in cytology, and subsequent histological diagnoses and cancer risk.Material and methodsAll women in Norway with atypical glandular cells of undetermined significance (AGUS), adenocarcinoma in situ (ACIS) and normal/benign cells, but absence of endocervical or metaplastic cells (NC‐NEC) in their first cytology during 1992‐2014 (NC‐NEC; 2005‐2014), recorded in the Cancer Registry of Norway, were included (n = 142 445). Histology diagnoses (stratified by age) within 1 and 3 years after cytology were examined. The Nelson‐Aalen cumulative hazard function for gynecological cancer risk was displayed.ResultsThe majority of AGUS and particularly ACIS were followed with histology within 1 and 3 years. Cervical intraepithelial neoplasia (CIN) lesions were more common in women <35 than in women ≥35 years. Cervical adenocarcinoma followed 13% of ACIS after 1 and 3 years. After ACIS and AGUS, cervical adenocarcinoma was the most frequent cancer subtype. Cumulative risks of cervical adenocarcinoma following ACIS, AGUS and NC‐NEC were 3.5%, 0.9% and 0.05%, respectively, after 22, 22 and 9 years of follow‐up.ConclusionsThere was a high‐risk of glandular malignancies after AGUS and ACIS in cytology. If effective treatment of pre‐cancer and early cancer is available, cytology screening provides some level of prevention of adenocarcinoma. Lack of glandular cells did not entail a higher cancer risk.

The impact of local symptoms on health‐related quality of life in vulvar cancer survivors—A nationwide prospective study

AbstractIntroductionVulvar cancer may cause serious local symptoms that may impact negatively on the woman's health‐related quality of life (HRQOL). However, knowledge about the prevalence of vulvar and lymphedema symptoms at diagnosis and during follow‐up is limited. The aim of this study was to evaluate the longitudinal development of vulvar and lymphedema symptoms as well as the trajectory of HRQOL in women with vulvar cancer. Furthermore, associations between vulvar symptoms and HRQOL were investigated.Material and MethodsIn this nationwide prospective cohort study, women completed validated patient‐reported outcome measures; the EORTC‐QLQ C30 and the EORTC‐QLQ‐VU34 at diagnosis, three, and 12 months post‐treatment. Mean scores of symptom‐ and functioning scales were calculated over time. Heatmaps were used to visualize proportional changes in the prevalence of symptoms at baseline and 12 months after treatment. Linear mixed‐effects models with patient‐specific random intercepts were specified to estimate changes in mean scores of HRQOL over time. Additionally, adjusted linear mixed‐effects models were applied to investigate the effect of the most prevalent vulvar symptom on HRQOL. The study has been registered at ClinicalTrials.gov (NCT 04152512).ResultsBetween 2019 and 2021, 153 women consented to participate in the study, and 140 (92%) completed the patient‐reported outcome measures at least once. In total, 105 (69%) completed the patient‐reported outcome measures at all three time points. The most prevalent reported symptom was itchy, irritated skin in the vulva, which decreased from 82% at diagnosis to 56% 12 months after treatment. All vulvar symptoms, except narrowing of the vaginal entrance, improved over time but persisted in large proportions of the women. Women with severe vulvar symptoms reported a significant decline in HRQOL. A deterioration of leg swelling symptoms was reported by 33% of the women. Emotional‐, role‐, social‐, and cognitive functioning, global and mental health improved significantly after treatment.ConclusionLocal vulvar symptoms were highly prevalent at diagnosis; however, as most aspects of HRQOL, they improved significantly during the first year of follow‐up. Severe vulvar symptoms were associated with impaired HRQOL. Symptoms of leg lymphedema increased after treatment. © 2025 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Long‐term quality of life, vulvar symptoms, and sexual functioning: A cross‐sectional study of Norwegian vulvar cancer survivors

AbstractIntroductionVulvar cancer survivors are at risk of experiencing impaired health‐related quality of life and sexual functioning after treatment. However, studies on survivorship challenges, particularly several years after treatment, are scarce. Our aim was to assess health‐related quality of life in Norwegian vulvar cancer survivors more than 5 years after treatment and to compare reported vulvar symptoms and sexual functioning with women from a normative sample of the general Norwegian female population.Material and MethodsPatients treated primarily for early‐stage vulvar squamous cell carcinoma at the Norwegian Radium Hospital between 2006 and 2016 were invited to participate. Health‐related quality of life, vulvar symptoms, and sexual functioning were assessed using the EORTC QLQ‐C30 and EORTC QLQ‐VU34. To recruit a normative sample, the EORTC QLQ‐VU34 was also distributed to a sample of Norwegian women with no prior history of cancer. EORTC QLQ‐C30 scores among vulvar cancer survivors were compared to “thresholds for clinical importance.” EORTC QLQ‐VU34 scores among cancer survivors were compared to those of the normative sample.ResultsA total of 44 (57%) of 77 vulvar cancer survivors completed the questionnaires, and 334 women from the general population were included for the normative sample. A considerable proportion of cancer survivors reported clinically relevant problems: 43% reported impaired physical functioning, while 30% experienced impaired emotional, cognitive, and social functioning. Genital and groin symptoms were significantly more common among cancer survivors than among women in the normative sample. Fewer vulvar cancer survivors were sexually active (9/44 (20%) versus 232/334 (69%)) and they reported a higher degree of sexual dysfunction compared to the normative sample.ConclusionsVulvar cancer survivors reported impaired health‐related quality of life even several years after treatment. Vulvar complaints and impaired sexual functioning were more common among vulvar cancer survivors than among women from the normative sample.

Differentiated vulvar intraepithelial neoplasia long‐term follow up and prognostic factors: An analysis of a large historical cohort

AbstractIntroductionDifferentiated vulvar intraepithelial neoplasia (dVIN) is a high‐risk preinvasive vulvar lesion and precursor of human papillomavirus‐independent vulvar squamous cell carcinoma (VSCC). Due to its rarity, literature data on its malignant potential are scant. The aim of the study is to assess the risk of developing VSCC in patients surgically treated for dVIN not associated with VSCC (solitary dVIN) and the risk of VSCC recurrence in patients treated for dVIN associated with VSCC (dVIN‐VSCC) at first diagnosis.Material and methodsA historical cohort study was performed in a northern Italy referral center for vulvar neoplasms. All consecutive women surgically treated for histologically confirmed dVIN from 1994 to 2021 were collected. Primary outcome was cancer risk or recurrent cancer risk, secondary outcomes were risk factors associated with VSCC development or recurrence. Kaplan–Meier method and log‐rank test were used to estimate cancer risk or recurrent cancer risk differences and uni‐ and multivariate Cox regression analyses to identify risk factors associated with VSCC development in solitary dVIN and recurrence of dVIN‐VSCC.ResultsSeventy‐six patients with dVIN at preoperative biopsy were included: at excisional specimens 44 were solitary dVIN and 32 were dVIN‐VSCC. The absolute risk of VSCC development after solitary dVIN treatment was 43.2% with median time to to VSCC diagnosis of 25.4 months (range 3.5–128.0 months). VSCC recurrence absolute risk in treated dVIN‐VSCC patients was 31.3% with median time to VSCC recurrence of 52.9 months (range 6.5–94.8 months). At uni‐ and multivariate regression analyses, only compliant topical ultrapotent corticosteroid treatment after solitary dVIN excision showed an ability to prevent VSCC development. No protective effect by corticosteroid treatment was shown for VSCC recurrence in dVIN‐VSCC patients. Smoking was associated with higher cancer recurrence risk in dVIN‐VSCC patients on both uni‐ and multivariate regression analyses.ConclusionsPatients with dVIN have a high risk of developing both primary and recurring VSCC. Early recognition, long‐term follow up, and compliant ultrapotent topical corticosteroid treatment are recommended.

Vulvar cancer incidence and net survival in Sweden 1960 to 2019: A population‐based national study

AbstractIntroductionVulvar cancer is a rare gynecological cancer affecting mostly older women. The aim of this population‐based study was to investigate the incidence and net survival of vulvar cancer in Swedish women from 1960 to 2019.Material and methodsData were retrieved from the mandatory Swedish Cancer Registry consisting of all women diagnosed with vulvar cancer between 1960 and 2019. Only women with a morphologically verified diagnosis of vulvar cancer were included. The individuals were then further matched with the Swedish Death Registry up until May 31, 2020.ResultsIn total, 8499 women were included with the following morphologies: squamous cell carcinoma 7250 (85.8%), malignant melanoma 539 (6.4%), adenocarcinoma 401 (4.8%) and other: 259 (3.1%). More than 50% of vulvar cancer cases occurred in women aged between 65 and 84 years of age. The 5‐year age‐standardized net survival increased from 53.0% (95% confidence interval [CI] 48.9–57.5) in 1960 to 72.1% (95% CI 68.8–75.5) in 2019. The proportion of adenocarcinoma among all cases increased from 2.0% to 8.7% between the 1960s and 2010s and an increase in age‐standardized 5‐year net survival was found for adenocarcinoma.ConclusionsThe age‐standardized incidence of vulvar cancer cases in Sweden was stable between 1960 and 2019. During the study period, an increase in adenocarcinoma and a decrease in malignant melanoma cases was found. Five‐year net survival increased by 20 percent units during the study period. For squamous cell carcinoma, an increased age‐specific 5‐year net survival was observed for all age groups, apart for women aged ≥85.

Anxiety and depression among women with newly diagnosed vulvar cancer – A nationwide longitudinal study

AbstractIntroductionOur objective was to investigate the trajectories of anxiety, depression, emotional and social functioning in women with newly diagnosed vulvar cancer from the time of diagnosis to 12 months after treatment. A further aim was to identify risk factors for high levels of anxiety.Material and methodsPROVE (PROspective Vulvar Cancer Evaluation) is a nationwide longitudinal cohort study investigating quality of life in women with newly diagnosed vulvar cancer by the following validated patient‐reported outcome measures at diagnosis, and 3 and 12 months after treatment: The Hospital Anxiety and Depression Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Vulvar module VU34. Mean scores, changes over time and associations were analyzed by generalized estimated equations and log‐linear regression models, adjusted for possible confounders.ResultsBetween 2019 and 2021, 105 (69%) women completed the questionnaires at all three time points. At diagnosis, 42% of the women reported elevated anxiety levels, decreasing significantly to 30% during the first 12 months. Insomnia, persisting vulvar symptoms and high information needs were significantly associated with a high level of anxiety (relative risk [RR] 2.1, 95% CI 1.2–3.7 for insomnia; RR 2.8, 95% CI 1.7–4.6 for vulvar symptoms, RR 2.7, 95% CI 1.5–4.9 for information needs). We found a trend towards a higher level of anxiety in younger women (<65 years: RR 1.5, 95% CI 1.0–2.5). Participants reported a low and stable prevalence of depression (14%) and high social functioning throughout the study period.ConclusionsWomen with newly diagnosed vulvar cancer report a high level of anxiety at diagnosis. Despite a significant improvement, anxiety remains widely prevalent during the first year of follow‐up. Targeting insomnia, vulvar symptoms and unmet needs may decrease anxiety during surveillance.

Time trends in human papillomavirus prevalence and genotype distribution in vulvar carcinoma in Norway

AbstractIntroductionApproximately 25%–43% of all vulvar carcinomas are associated with human papillomavirus (HPV). In many countries, vulvar carcinoma incidence rates are increasing, possibly due to greater HPV exposure. However, studies exploring changes in HPV prevalence and genotype distribution in vulvar carcinoma over time are scarce. Our aim was to evaluate time trends in HPV prevalence and genotype distribution in vulvar squamous cell carcinoma in an unselected, nationwide sample of Norwegian women. Further, we explored clinical and histopathological aspects in relation to HPV status and investigated whether HPV status was associated with survival.Material and methodsAll vulvar squamous cell carcinoma cases from 1970–1975 and 2000–2005 were extracted from the Cancer Registry of Norway and corresponding tissue blocks were retrieved. After detailed histology review, HPV testing was conducted using real‐time TaqMan PCR. Overall survival rates were calculated using the Kaplan–Meier method. Multivariable Cox regression analysis was performed to estimate hazard ratios adjusted for age at diagnosis, stage and diagnostic period.ResultsHistological review was performed on 352 vulvar squamous cell carcinoma cases. We were able to obtain valid HPV analysis results for 282 cases, Overall, 29.8% (95% CI 24.5%–35.5%) of cases were high‐risk HPV (hrHPV)‐positive. When comparing the two periods, we found that the percentage of hrHPV‐positive tumors increased significantly from 23% (95% CI 16.0%–31.4%) in 1970–1975 to 35.3% (95% CI 27.8%–43.3%) in 2000–2005 (P = 0.025). The predominant genotypes were HPV 16 (73%), HPV 33 (21%), and HPV 18 (6%), with similar distributions in both periods. In the more recent cohort, several additional genotypes were detected: HPV 6, 11, 39, 45, 52, 58 and 66 were found in smaller percentages, ranging from 1.8% to 3.6%. In univariate analysis, patients with HPV‐positive tumors showed improved overall survival compared with patients with HPV‐negative tumors (hazard ratio [HR] 0.65, 95% CI 0.48–0.86).ConclusionsThe prevalence of HPV in vulvar squamous cell carcinomas in Norway was significantly higher in 2000–2005 than in 1970–1975. The three predominant genotypes were HPV 16, 33 and 18 in both time periods. However, several other HPV genotypes have emerged over the last decades. HPV‐positivity was associated with better overall survival.

Can late lymphoscintigraphy be omitted in the sentinel node procedure in early‐stage vulvar cancer?

AbstractIntroductionIn the Netherlands, the sentinel lymph node procedure protocol consists of preoperative lymphoscintigraphy combined with intraoperative blue dye for identifying sentinel lymph nodes in early vulvar squamous cell carcinoma. This study aimed at investigating the role of early and late lymphoscintigraphy.Material and methodsFrom January 2015 to January 2019, early and late lymphoscintigraphies of 52 women were retrospectively analyzed. Lymphoscintigraphy was performed 30 minutes (early) and 2.5–4 hours (late) after vulvar injection of 99mTc‐labeled nanocolloid. We calculated the concordance correlation coefficient (CCC) between number of sentinel lymph nodes detected on both images using the Lins concordance coefficient and correlated with clinicopathological data.ResultsThirty‐four women had a midline tumor and 18 had a lateral tumor. Detection rates with early and late scintigraphy were 88.5% and 98.1%, respectively. Median number of detected nodes was 1.0 (0–7) and 2.0 (0–7). Good statistical correlation between number of sentinel lymph nodes detected on early and late imaging was found (CCC = 0.76) in most patients. In 18 women (35%) a mismatch occurred: a higher number of nodes was detected on late imaging. In 11 of 18 women re‐injection was performed because no sentinel lymph nodes were visualized on early images. Late imaging and intraoperative detection showed a good statistical correlation (CCC = 0.61). One woman showed an isolated groin recurrence despite negative sentinel lymph nodes.ConclusionsThis study showed good statistical correlations between early and late scintigraphy in most patients. However, in 35% of women late scintigraphy detected more nodes. In case of poor visualization after the first scintigraphy, re‐injection should be considered. Late scintigraphy is probably helpful in confirming successful re‐injection and in showing deviating lymph flow in women with failed mapping after the first injection and successful re‐injection. Because missing metastatic sentinel lymph nodes often leads to a poor prognosis, we prefer optimal correlations between imaging and intraoperative identification. Hence, late scintigraphy cannot be safely omitted.

Contralateral lymph node metastases in patients with vulvar cancer and unilateral sentinel lymph node metastases

AbstractIntroductionThe risk of contralateral lymph node metastases following unilateral sentinel lymph node (SLN) metastases in patients with vulvar cancer(s) remains to be systematically assessed.Material and methodsWe performed a multicenter, retrospective registry‐based study of 476 patients with vulvar cancer. The primary outcome measure was the rate of contralateral non‐SLN metastases in the case of positive unilateral SLN.ResultsOut of 476 patients with primary vulvar cancer, 202 received SLN biopsy: 58 unilateral and 144 bilateral. Out of 66 patients with unilateral metastatic SLN, 62 (93.9%) received contralateral lymphadenectomy—18 after unilateral and 44 after bilateral SLN biopsy. In the study group, 132 SLN were assessed with a median number of 2 (range 1–4) per patient and 76 of these were positive. Lymph node‐positivity was associated with advanced tumor stage, as well as lymph and vascular space invasion. In the group of patients with bilateral inguino‐femoral lymphadenectomy, 1004 lymph nodes were resected with a median number of 15 (range 10–29) per patient. After full dissection of the inguino‐femoral lymph nodes, no contralateral non‐SLN metastases were found.ConclusionsThe risk of contralateral non‐SLN metastases in patients with unilateral SLN metastases was low. Therefore, the impact of contralateral lymphadenectomy on patient survival should be investigated in further studies.

Salvage surgery for patients with residual disease after chemoradiation therapy for locally advanced cervical cancer: A systematic review on indication, complications, and survival

AbstractIntroductionStandard treatment for locally advanced cervical cancer is chemoradiation therapy. Treatment with chemoradiation therapy harbors a risk of local residual disease, which can be curatively treated with salvage surgery, but the risk of complications following surgical procedures in radiated tissue is not negligible. The presence of residual disease can be radiologically and/or histologically diagnosed. The objective of this study is to describe studies that report on salvage surgery for patients with locally advanced cervical cancer after primary treatment with chemoradiation therapy. Therefore, we assessed the method of determining the presence of residual disease, the risk of complications, and the survival rate after salvage surgery.Material and methodsPubMed, EMBASE, and the Cochrane database were searched from inception up to 6 March 2020. Titles and abstracts were independently assessed by two researchers. Studies were eligible for inclusion when patients had locally advanced cervical cancer with radiologically suspected or histologically confirmed residual disease after chemoradiation therapy, diagnosed with a CT, MRI, or PET‐CT scan, or biopsy. Information on complications after salvage surgery and survival outcomes had to be reported. Methodological quality of the articles was independently assessed by two researchers with the Newcastle‐Ottawa scale.ResultsOf the 2963 screened articles, six studies were included, representing 220 women. A total of 175 patients were treated with salvage surgery, of whom 27%‐100% had residual disease on the surgery specimen. Of the 161 patients treated with salvage surgery based on positive biopsy results, 72%‐100% showed residual disease on the surgery specimen. Of the 44 patients treated with salvage surgery based on suspected residual disease on radiology, 27%‐48% showed residual disease on the salvage surgery specimen. A total of 105 complications were registered in 175 patients treated with salvage surgery. The overall survival rate after salvage surgery was 69% (mean follow‐up period of 24.9 months).ConclusionsIt is necessary to confirm residual disease by biopsy before performing salvage surgery in patients with locally advanced cervical cancer primarily treated with chemoradiation therapy. Salvage surgery only based on radiologically suspected residual disease should be avoided to prevent unnecessary surgery and complications.

Immune checkpoint blockades in gynecological cancers: A review of clinical trials

AbstractAdvanced and recurrent gynecological cancers are associated with a poor prognosis and there is still a lack of effective treatments. Immune checkpoint blockade (ICB) therapy is an important element of cancer‐targeted therapy and immunotherapy. The programed cell death protein 1 (PD‐1) and cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) pathways are the two main targets of ICB. In this study, we provide a comprehensive review of clinical evidence concerning ICB therapy in gynecological cancers and discuss future implications. All clinical trials of ICB therapy in gynecological cancers were reviewed. We searched ClinicalTrials.gov to collect data from completed and ongoing clinical trials. The clinical evidence regarding the efficacy of ICB agents in gynecological cancers were discussed. Six phase III clinical trials have reported their results of primary outcomes, and a total of 25 phase II clinical trials have been completed. As revealed in phase III trials, pembrolizumab (a PD‐1 antibody) improved the overall survival and progression‐free survival in endometrial cancer patients with mismatch repair deficiency and cervical cancer patients with expressions of PD‐L1. Based on these findings, pembrolizumab was approved by the Food and Drug Administration and European Medicines Agency as a cancer medication used to treat certain patients with endometrial cancer or cervical cancer. Other PD‐1 antibodies, including dostarlimab and cemiplimab, also showed antitumor efficacy in clinical trials. Dostarlimab treatment showed an encouraging response rate in endometrial cancer patients with mismatch repair deficiency. Cemiplimab treatment led to a longer overall survival and a lower risk of death than chemotherapy among patients with recurrent cervical cancer. Three completed phase III trials investigated anti‐PD‐L1 agents (atezolizumab and avelumab) in the treatment of ovarian cancer. The results were not encouraging. Other strategies of ICB therapy which had showed potential clinical benefit in the treatment of gynecological cancers in early‐phase trials need to be further evaluated in late‐stage trials. The antitumor efficacy of ICB therapy is promising, and the key to making further progress in the treatment of gynecological cancers is to identify more biomarkers and explore innovative combination treatments with other targeted therapies.

High‐risk HPV testing vs liquid‐based cytology for cervical cancer screening among 25‐ to 30‐year‐old women: A historical cohort study

AbstractIntroductionHigh‐risk human papilloma virus (hrHPV) DNA testing is more sensitive than cytology screening, achieving greater protection against cervical cancer. Controversy exists regarding the preferred screening method for women 25–30 years of age. At this age, infection with HPV is common and usually transient. Consequently, hrHPV screening in this age group is fraught with high false‐positive screening results, leading to more colposcopies and unnecessary treatments with the potential for harm. In the present study, we aimed to compare the results of two screening methods in relation to high‐grade cervical intraepithelial lesion detection rate in the young age group of 25–30 years.Material and methodsRetrospective information on cervical cytology, hrHPV testing, colposcopy referrals and histologic results, from one screening round, were retrieved from the Maccabi HealthCare Health Maintenance Organization centralized database during the study period from March 1, 2017 to April 1, 2019 for 25‐ to 30‐year‐old women. Screening with hrHPV testing for types 16, 18 and 12 other hrHPV types was compared with the conventional PAP liquid‐based cytology (LBC) test. Odds ratio (OR) of detection with 95% confidence interval (CI) was calculated for cervical intraepithelial neoplasia (CIN) grade 3 or higher (CIN 3+).ResultsDuring the study period, 42 244 women 25–30 years old underwent cervical cancer screening; of them, 20 997 were screened with LBC between March 1, 2017 and March 1, 2018 and compared with 21 247 who were screened with hrHPV between April 1, 2018 and April 1, 2019. Testing for hrHPV resulted in a higher colposcopy referral rate compared with primary LBC screening: 9.8% vs 7.8%, respectively; (OR 1.28; 95% CI 1.2–1.37; p < 0.001). Screening with hrHPV led to significantly higher detection of CIN 3+ lesions (OR 1.4; 95% CI 1.2–1.6; p < 0.001) compared with LBC. HPV infections with non‐16/18 hrHPV (other hrHPV) were the most prevalent (84.8%).ConclusionsIn women 25–30 years old, primary hrHPV screening was associated with a higher detection rate of CIN 3+ compared with cytology screening and should be considered for primary screening in this age group.

Cervical neoplasia in relation to socioeconomic and demographic factors – a nationwide cohort study (2002–2018)

AbstractIntroductionCervical cancer is a major cause of mortality and morbidity. We aimed to estimate the association between sociodemographic factors and cervical neoplasia.Material and methodsIn this Swedish nationwide open cohort study, 4 120 557 women aged ≥15 years at baseline were included between January 1, 2002 and December 31, 2018. The two outcomes were cervical cancer and carcinoma in situ identified in the Swedish Cancer Register. Sociodemographic factors (age, education level, family income level, region of residency, country of origin) were the main predictors. Incidence rates per 10 000 person‐years were calculated. Cox regression was used to estimate hazard ratios. Sensitivity analyses were conducted, including parity, urogenital infections, alcohol‐ and drug‐use disorders, and chronic obstructive pulmonary disease (used as a proxy for tobacco abuse).ResultsIn 38.9 million person‐years of follow‐up, 5781 (incidence rate: 1.5, 95% confidence interval [CI] 1.4–1.5) and 62 249 (incidence rate 16.9, 95% CI 15.9–16.1) women were diagnosed with cervical cancer and carcinoma in situ, respectively. Women from Eastern Europe had a hazard ratio of 1.18 (95% CI 1.05–1.33) for cervical cancer compared with Swedish‐born women, while women from non‐Western regions were inversely associated with cervical cancer and carcinoma in situ. Women with a low education level had a hazard ratio of 1.37 (95% CI 1.29–1.45) for cervical cancer compared with women with a high education level.ConclusionsWomen from the Middle East and Africa living in Sweden seem to suffer less from cervical neoplasia, whereas women with low education and women from Eastern Europe seem to suffer more from cervical cancer.

Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high‐risk human papillomavirus‐positive population

AbstractIntroductionImmunostaining with p16INK4a (p16), a tumor‐suppressor surrogate protein biomarker for high‐risk human papillomavirus (hrHPV) oncogenic activity, may complement standard hematoxylin and eosin (H&E) histology review, and provide more objective criteria to support the cervical intraepithelial neoplasia (CIN) diagnosis. With this study we assessed the impact of p16 immunohistochemistry on CIN grading in an hrHPV‐based screening setting.Material and methodsIn this post‐hoc analysis, 326 histology follow‐up samples from a group of hrHPV‐positive women were stained with p16 immunohistochemistry. All H&E samples were centrally revised. The pathologists reported their level of confidence in classifying the CIN lesion.ResultsCombining H&E and p16 staining resulted in a change of diagnosis in 27.3% (n = 89) of cases compared with the revised H&E samples, with a decrease of 34.5% (n = 18) in CIN1 and 22.7% (n = 15) in CIN2 classifications, and an increase of 18.3% (n = 19) in no CIN and 20.7% (n = 19) in CIN3 diagnoses. The level of confidence in CIN grading by the pathologist increased with adjunctive use of p16 immunohistochemistry to standard H&E.ConclusionsThis study shows that adjunctive use of p16 immunohistochemistry to H&E morphology reduces the number of CIN1 and CIN2 classifications with a proportional increase in no CIN and CIN3 diagnoses, compared with standard H&E‐based CIN diagnosis alone. The pathologists felt more confident in classifying the material with H&E and p16 immunohistochemistry than by using H&E alone, particularly during assessment of small biopsies. Adjunctive use of p16 immunohistochemistry to standard H&E assessment of CIN would be valuable for the diagnostic accuracy, thereby optimizing CIN management and possibly decreasing overtreatment.

Cervical cancer mortality in Norway according to screening attendance and age

AbstractIntroductionThe association between cervical cancer screening and reduction of cervical cancer has been dealt with in much research. However, little has been published on the association between screening and cervical cancer mortality. We assessed cervical cancer deaths according to screening history, histopathology, and age among women in, under, and above screening age.Material and methodsIn this nationwide, registry‐based case–control study from Norway, we included 817 cervical cancer deaths in women diagnosed with cervical cancer in the period 1998–2009. We matched each case with 10 population‐based controls free from cervical cancer, obtained by density‐based sampling. Odds ratios (ORs) with 95% confidence intervals (CIs) for the association between screening attendance and cervical cancer mortality were estimated using conditional logistic regression models.ResultsOf all fatal cervical cancers, 35% were diagnosed among women over screening age and altogether, 83% were either in age groups not covered by the screening program or in non‐attenders of screening age. The estimated risk reduction associated with a cytology test in the preceding 3.5 years was 80% in screening age 25–69 years (OR 0.20; 95% CI 0.16–0.24) with the largest reduction in squamous cell carcinomas (84%) but also a substantial estimated risk reduction of 65% for adenocarcinomas. The associated risk reduction was strongest in women aged 45–69 years, with ORs in the range 0.09–0.18, compared with ORs 0.42–1.35 in women aged 25–39 years.ConclusionsTo reduce the mortality of cervical cancer, screening programs should focus on increasing adherence to the program, as half of all the fatal cases were in the non‐attender group. Further assessments regarding the potential preventive impact of extending screening to women over the current screening age should be considered.

Human papillomavirus vaccination in women undergoing excisional treatment for cervical intraepithelial neoplasia and subsequent risk of recurrence: A systematic review and meta‐analysis

AbstractIntroductionIn this review and meta‐analysis we aimed to investigate whether human papilloma virus (HPV) vaccination administered after excisional treatment of cervical intraepithelial neoplasia (CIN) is associated with a reduced risk of recurrence of CIN grade 2 or worse (CIN2+).Material and methodsWe performed a systematic literature search in three online databases through June 2021. Observational studies and randomized controlled trials (RCTs) were eligible for inclusion if the prophylactic HPV vaccine was administered after excisional treatment for histologically verified CIN. Only English language literature was included. The primary outcome measure was recurrence of CIN2+ after treatment. A meta‐analysis was performed using fixed and random‐effects models, and results were reported as pooled odds ratios (OR) with 95% confidence intervals (95% CI). Quality assessment was performed using ROB2‐tool for RCTs and ROBINS‐I for observational studies. The protocol was registered in PROSPERO (CRD42021238257).ResultsA total of 1561 studies were identified, of which nine, including 19 971 women, were included. Two studies were RCTs and seven were observational studies. Using the fixed‐effect model on the two RCTs, the OR for recurrence of CIN2+ was 0.29 (95% CI 0.16–0.53). Due to considerable heterogeneity in observational studies, the random‐effects model was used to estimate pooled OR for CIN2+ recurrence in these studies. Thus, using unadjusted data from observational studies, the OR for CIN2+ recurrence was 0.35 (95% CI 0.18–0.67), whereas when using adjusted data, the OR for CIN2+ recurrence was 0.54 (95% CI 0.21–1.35). However, quality assessment revealed a serious risk of bias for the majority of the studies included.ConclusionsHPV vaccination post‐treatment was associated with a significantly reduced risk of CIN2+ recurrence when using unadjusted estimates from observational studies and RCTs. We found no significant effect of HPV vaccination on risk of CIN2+ recurrence when using the outcome measure from observational studies with the least risk of bias. Large, well‐designed randomized placebo‐controlled trials are needed to determine whether post‐treatment HPV vaccination should be recommended to all women undergoing excisional treatment for CIN.

Evidence of latent HPV infection in older Danish women with a previous history of cervical dysplasia

AbstractIntroductionUnderstanding whether human papillomavirus (HPV) may establish latency in the uterine cervix is important. A better understanding of HPV natural history is useful for clinical counseling of women attending screening and to accurately inform health prevention strategies such as screening and HPV vaccination. We evaluated the extent of latent HPV infections in older women with a history of abnormal cytology.Material and MethodsWe conducted a cross‐sectional study in Aarhus, Denmark, from March 2013 through April 2015. Women were enrolled if they underwent cervical amputation or total hysterectomy because of benign disease. Prior to surgery, women completed a questionnaire and a cervical smear was collected for HPV testing and morphological assessment. For evaluation of latency (i.e., no evidence of active HPV infection, but HPV detected in the tissue), we selected women with a history of abnormal cervical cytology or histology, as these women were considered at increased risk of harboring a latent infection. Cervical tissue underwent extensive HPV testing using the SPF10‐DEIA‐LipA25 assay.ResultsOf 103 women enrolled, 26 were included in this analysis. Median age was 55 years (interquartile range [IQR] 52–65), and most women were postmenopausal and parous. The median number of sexual partners over the lifetime was six (IQR 3–10), and 85% reported no recent new sexual partner. Five women (19.2%) had evidence of active infection at the time of surgery, and 19 underwent latency evaluation. Of these, a latent infection was detected in 11 (57.9%), with HPV16 being the most prevalent type (50%). Nearly 80% (n = 14) of the 18 women with a history of previous low‐grade or high‐grade cytology with no treatment had an active or latent HPV infection, with latent infections predominating. HPV was detected in two of the six women with a history of high‐grade cytology and subsequent excisional treatment, both as latent infections.ConclusionsHPV can be detected in cervical tissue specimens without any evidence of an active HPV infection, indicative of a latent, immunologically controlled infection. Modeling studies should consider including a latent state in their model when estimating the appropriate age to stop screening and when evaluating the impact of HPV vaccination.

“I feel reassured, but there is no guarantee.” How do women with a future childbearing desire respond to active surveillance of cervical intraepithelial neoplasia grade 2? A qualitative study

AbstractIntroductionIn Denmark, women with a future childbearing desire diagnosed with cervical intraepithelial neoplasia grade 2 (CIN2) are recommended active surveillance instead of excisional treatment. However, we have limited and contradictory knowledge about how active surveillance of CIN2 may affect women emotionally. The aim of this study was to explore thoughts and emotional responses in women undergoing active surveillance of CIN2 and to explore how active surveillance may affect women’s future childbearing desire.Material and methodsThis qualitative study was conducted in the gynecological outpatient clinic, the Department of Obstetrics and Gynecology, Gødstrup Hospital, Denmark. Women of childbearing age undergoing active surveillance with colposcopy, biopsy and smear every 6 months due to CIN2 were eligible for enrollment. In‐depth semi‐structured interviews were conducted. The interviews were audiotaped and transcribed verbatim. A thematic analysis was performed using a phenomenological approach.ResultsA total of 20 women were included. All women experienced nervousness and anxiety when they were diagnosed with CIN2 initially. Their main concern was whether they had cancer. Most women carried on with their everyday lives with only minor occasional worries about CIN2, often prompted just before check‐up. However, some women were particularly nervous and found the period between check‐ups frustrating and challenging. Women did not want to postpone their plans for pregnancy because of CIN2, but experienced the worries and check‐ups associated with active surveillance as disruptive elements in their family planning. Women preparing for fertility treatment had their startup unnecessarily delayed due to active surveillance of CIN2, as clinical guidelines were inconsistent across subspecialties. Various factors influenced women’s emotional well‐being: life circumstances, information needs, and mental and physical discomfort during colposcopic examination.ConclusionsWomen felt that worries and check‐ups due to active surveillance of CIN2 were disrupting elements in their family planning, although they did not affect their every‐day life. Some women, however, were particularly anxious, demonstrating the importance of including women’s experiences and preferences in clinical counseling. The fact that fertility treatment was delayed due inconsistent guidelines across subspecialties, suggests a need for a revision of current guidelines.

The prognostic value of the number of positive lymph nodes and the lymph node ratio in early‐stage cervical cancer

AbstractIntroductionTo establish the impact of the number of lymph node metastases (nLNM) and the lymph node ratio (LNR) on survival in patients with early‐stage cervical cancer after surgery.Material and methodsIn this nationwide historical cohort study, all women diagnosed between 1995 and 2020 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA2–IIA1 cervical cancer and nodal metastases after radical hysterectomy and pelvic lymphadenectomy from the Netherlands Cancer Registry were selected. Optimal cut‐offs for prognostic stratification by nLNM and LNR were calculated to categorize patients into low‐risk or high‐risk groups. Kaplan–Meier overall survival analysis and flexible parametric relative survival analysis were used to determine the impact of nLNM and LNR on survival. Missing data were imputed.ResultsThe optimal cut‐off point was ≥4 for nLNM and ≥0.177 for LNR. Of the 593 women included, 500 and 501 (both 84%) were categorized into the low‐risk and 93 and 92 (both 16%) into the high‐risk groups for nLNM and LNR, respectively. Both high‐risk groups had a worse 5‐year overall survival (p < 0.001) compared with the low‐risk groups. Being classified into the high‐risk groups is an independent risk factor for relative survival, with excess hazard ratios of 2.4 (95% confidence interval 1.6–3.5) for nLNM and 2.5 (95% confidence interval 1.7–3.8) for LNR.ConclusionsPresenting a patient's nodal status postoperatively by the number of positive nodes, or by the nodal ratio, can support further risk stratification regarding survival in the case of node‐positive early‐stage cervical cancer.

Setting the record straight—Correcting uterine cancer incidence and mortality in the Nordic countries by reallocation of unspecified cases

AbstractIntroductionThe incidence of and mortality from cancers of the cervix uteri and corpus uteri are underestimated if the presence of uterine cancers, where the exact topography (site of origin) is not specified, is omitted. In this paper we present the corrected figures on mortality from and incidence of cervix and corpus uteri cancers in the Nordic countries by reallocating unspecified uterine cancer deaths and cases to originate either from the corpus uteri or cervix uteri. To further validate the accuracy of reallocation, we also analyzed how well the reallocation captures the changes occurring as the result of a transition in cause of death coding in Norway that took place in 2005.Material and MethodsThis study uses data available in the NORDCAN database, which contains aggregated cancer data from all the Nordic countries for the years 1960–2016. The unspecified uterine cancer cases and deaths were reallocated to either cervix uteri or corpus uteri based on the estimated probability that follows the distribution of cases and deaths with verified topography. The estimated proportions of cases and deaths for both cancers were calculated for each combination of age group, year, and country as a proportion of cases (and deaths, respectively) with known topography. Annual age‐standardized rates were calculated by direct age‐adjustment.ResultsThe proportions of unspecified uterine cancers were higher in the mortality data than in incidence data, with mean values for 1960–2016 ranging between 5.1% and 26.6% and between 0.2% and 6.8% by country, respectively. In the Nordic countries combined, the reallocation increased the number of cases by 4% and deaths by approximately 20% for both cancers. Finland was the only Nordic country where the mortality rate did not increase substantially after reallocation.ConclusionsThe reallocation procedure had a significant impact on mortality from cancers of the cervix and corpus uteri for countries where the proportion of cancer deaths coded as uterus, not otherwise specified, is substantial. More effort to validate cause of death data with incidence data from cancer registries is warranted to avoid erroneous conclusions of temporal trends based on uncorrected cancer burden.

Co‐testing in cervical screening among 40‐ to 42‐year‐old women is unreasonable

AbstractIntroductionThe screening program for cervical cancer in Sweden recommends the use of primary human papillomavirus (HPV) screening for women aged ≥30 to 65 years. Co‐testing with both HPV analysis and cytology is recommended at the first screening after the age of 40 years. To fulfil co‐testing, all screened women aged 40–42 years within the region of Skåne were co‐tested. The aim of the audit was to investigate the proportion of severe dysplasia as diagnosed by cytology and histological follow‐up among women with Aptima HPV‐negative tests. We also calculated the cost of adding the cytology to the HPV primary screening program.Material and MethodsThe local cytology registry was used to identify women aged 40–42 years who attended screening and were co‐tested during the 4 years from January 2017 to December 2020. The Aptima HPV messenger RNA assay detects 14 HPV types. For Aptima HPV‐negative women with high‐grade cytology or histological high‐grade squamous intraepithelial lesions (HSILs), we performed extended HPV typing for 40 HPV types with polymerase chain reaction using modified GP5+/6+ primers followed by a Luminex assay. To estimate the added cost of using cytology to identify each histologically confirmed cervical HSIL case among Aptima HPV‐negative women, we used the current cost of €21.2 per cytology evaluation at our laboratory.ResultsOf 19 599 women, 5.8% (1137/19 599) had abnormal cytology. Among Aptima HPV‐negative women, 0.11‰ (2/18 132) had histologically confirmed HSIL. One of the women was infected with HPV18 and the other with HPV73 at the diagnosis of HSIL. The calculated cost to find one HSIL, by adding cytology to HPV‐negative cases, was approximately €200 000.ConclusionsThe clinical benefit of a single cytology co‐test added to an HPV‐based screening program in women aged 40–42 years appears doubtful and economically unreasonable.

Publisher

Wiley

ISSN

0001-6349