Prognostic Value of Conization and Negative HPV After Conization in AIS and Early Stage Cervical Cancer

SUCCOR cone study: conization before radical hysterectomy

To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Protective Role of Conization Before Radical Hysterectomy in Early-Stage Cervical Cancer: A Propensity-Score Matching Study

The purpose of this study was to assess the prognostic role and the perioperative outcomes of conization performed before radical hysterectomy in early-stage cervical carcinoma. This multicenter, retrospective observational cohort study included patients with FIGO 2009 stage IB1 cervical carcinoma treated with radical hysterectomy between June 2004 and June 2019. Patients were divided into two groups according to conization before radical surgery. One-to-one case-control matching was used to adjust the baseline characteristics. A total of 332 patients were included after propensity matching (166, 50% in each group). Twenty-four of 166 (14.4%) and 142 of 166 (85.6%) conization patients had negative and positive surgical margins on the conization specimen, respectively. No difference in intra- and postoperative complications was noted between the two groups (p = 0.542 and p = 0.180, respectively). Patients undergoing conization before radical hysterectomy received less adjuvant treatment (p 20 mm and no conization before radical hysterectomy (p = 0.011 and p = 0.018, respectively). The only independent variable influencing OS was pathologic tumor diameter >20 mm (p = 0.020). Conization before radical hysterectomy was associated with improved DFS and lower probability of receiving adjuvant treatment. No difference in perioperative complications and OS was evident. Tumor diameter >20 mm was found to be the only independent risk factor affecting OS in both groups.

Simple conization and pelvic lymphadenectomy in early-stage cervical cancer: A retrospective analysis and review of the literature

To evaluate the feasibility of cervical conization and laparoscopic pelvic lymphadenectomy as a fertility-sparing surgery to treat early-stage cervical cancer. We conducted a retrospective analysis from a prospectively maintained database of patients with stage IA1-IB1 grossly invisible cervical cancers undergoing conization plus laparoscopic lymphadenectomy between January 2014 and July 2019. Forty patients were identified. Five patients (12.5%) had stage IA1 with lymphovascular space invasion, 21 (52.5%) had stage IA2, and 14 (35.0%) had stage IB1. All of the patients had tumors <2 cm. Histology included 35 (87.5%) squamous-cell carcinomas, three (7.5%) adenocarcinomas, and two (5.0%) adenosquamous carcinomas. Median duration of the procedure was 105 min (range, 31-219), and the median estimated blood loss was 50 ml (range, 30-200). One patient received abdominal radical trachelectomy due to the presence of positive margin after conization. Three patients developed postoperative cervical stenosis. After a median follow-up of 35 months (range, 8-74), only one patient (2.5%) developed a recurrence in the remaining cervix, and no patients died. Four of 17 patients attempting to conceive had a spontaneous pregnancy: three delivered at term and one was currently pregnant. Cervical conization and pelvic lymphadenectomy seems to be an acceptable treatment for well-selected patients with low-risk, early-stage cervical cancer who wish to preserve fertility. It offers excellent oncologic outcomes, low perioperative morbidities, and good reproductive results. Further large prospective studies are warranted to prove the effectiveness of this surgery.

Recurrence Rates in Patients With Cervical Cancer Treated With Abdominal Versus Minimally Invasive Radical Hysterectomy: A Multi-Institutional Retrospective Review Study

PURPOSE To compare the disease-free survival (DFS) between open and minimally invasive radical hysterectomies (RH) performed in academic medical institutions METHODS Retrospective multi-institutional review of patients undergoing RH for stage IA1 (with lymphovascular invasion), IA2, and IB1 squamous, adenocarcinoma, or adenosquamous carcinoma between January 1, 2010 and December 31, 2017. RESULTS Of 815 patients, open RH was performed in 255 cases (29.1%) and minimally invasive RH in 560 cases (70.9%). There were 19 (7.5%) recurrences in the open RH and 51 (9.1%) recurrences in the minimally invasive group ( P = .43). Risk-adjusted analysis revealed that minimally invasive RH was independently associated with an increased hazard of recurrence (aHR, 1.88; 95% CI, 1.04 to 3.25). Other factors independently associated with an increased hazard of recurrence included tumor size, grade, and adjuvant radiation. Conization before surgery was associated with lower recurrence risk (aHR, 0.4; 95% CI, 0.23 to 0.71). There was no difference in OS in the unadjusted analysis (HR, 1.14; 95% CI, 0.61 to 2.11) or after risk adjustment (aHR, 1.01; 95% CI, 0.5 to 2.2). Of 264 patients with tumors ≤ 2 cm on final pathology (excluding those with no residual tumor on final pathology), 2/82 (2.4%) recurred in the open RH group and 16/182 (8.8%) in the minimally invasive RH group ( P = .058). In propensity score matching analysis, 7/159 (4.4%) recurrences were noted in the open RH group and 18/156 (11.5%) in the minimally invasive RH group ( P = .019). Survival analysis revealed an increased risk of recurrence in the minimally invasive group in propensity-matched cohort (HR, 2.83; 95% CI, 1.1 to 7.18) CONCLUSION In this retrospective series, patients undergoing minimally invasive radical hysterectomy, including those with tumor size ≤ 2 cm on final pathology, had inferior DFS but not overall survival in the entire cohort.

The Association Between Clearance of Human Papillomavirus After Conization for Cervical Cancer and Absence of Cancer

Objectives We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS). Materials Methods Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3–12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ. Results The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV–negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p &lt; .006). In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p &lt; .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%. Conclusions Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

Anna Myriam Perrone

Daniel Vázquez-Vicente

Denis Querleu

Enrique Chacon

Felix Boria

Jose Angel Minguez

Juan Luis Alcázar

Luigi Pedone Anchora

Luis Chiva

Marcin Jedryka

Mehmet Mutlu Meydanli

Nabil Manzour

Róbert Póka

CURRICULUM VITAE NAME: Dr.Robert Poka PhD BORN: 07.26.1960 ADDRESS: 7 St.István u., Nyíregyháza, 4400-Hungary Mobile: (36)-20-9216022 E-mail: pokar@med.unideb.hu WORK: Professor, Director, Dept.Ob/Gyn., Medical School, University of Debrecen Chairman of Gynaecological Oncology Unit Debrecen PO Box 37, 4012-Hungary Phone: (36)-52-255705, Fax: (36)-52-255705 E-mail: pokar@med.unideb.hu GRADUATED: University of Debrecen, Medical School, Hungary MD, Debrecen, 1984 QUALIFICATIONS: Obstetrician and Gynecologist Postgraduate Medical School, Budapest, 1988 Med.Habil., Univ.Debrecen, 2004 Clinical Oncologist, National Inst.Oncol., Budapest, 2008 Gynaecological Oncology Surgeon, Budapest, 2016 DEGREE: PhD, Budapest, 1995(16.326 MTA) Studies in the epidemiology, diagnostics and therapy of cervical cancer. STUDIES AND WORK EXPERIENCE ABROAD: August 1990 - May 1995 United Kingdom Work with Roger Peel of Leeds, Colin Richards in Caerphilly, and Professor Chris Hudson, David Glyn-Evans, Marcus Setchell and John Shepherd of London St.Bartholomew’s Hospital and Medical School SUMMARY OF RESEARCH AND CLINICAL ACTIVITY: His responsibilities cover the full spectrum of general obstetrics and gynecology on consultant level with special interest and experience in gynecologic oncology including radical surgery. He did clinical research in high risk obstetrics with special reference to pre-eclampsia and operative delivery. Obstetric and gynecologic aspects of thrombophilia are major areas of his current research interest. As clinical investigator, he contributed to several phase 2 and 3 international pharmaceutical projects including Epirubicin for ovarian cancer (Farmitalia), Provera for endometrial cancer (UpJohn), Diflucan for vaginal candidiasis (Pfizer), Synarel for endometriosis (Syntex), Taxol+Carboplatin for ovarian cancer (Bristol Myers), Mycosyst-Gyno for vaginal candidiasis (Richter), Basedoxifen (Wyeth). PUBLICATION ACTIVITY: 139 publications, 86 papers in extenso in peer reviewed journals, 39 in English, IF: 51.272, independent CIT: 252, 1 book, 5 book chapters, 3 first prize competition essays, 2 second prize competition essays, 2 best paper of the year award, 1 best lecture award, 132 scientific lectures in Hungarian, 29 in English, further 46 lectures in Hungarian and 19 in English co-authored, 27 undergraduate research projects tutored, 51 diploma thesis tutored ……………………………. ……………………………. Date Signature

Robert Fruscio

Tayfun Toptas

Vladyslav Sukhin

Ukrainian lead clinical researcher, Professor in Grigoriev Institute for Medical Radiology and Oncology, National Academy of Medical Sciences of Ukraine | Laureate of the Prize of the Cabinet of Ministers of Ukraine 2016 – 2021 Expert, Member of Expert council of the Ministry of education and science of Ukraine