Katrine Fuglsang

Nonepithelial ovarian cancer – the current clinical practice in the Nordic countries. Survey from the surgical subcommittee of the Nordic society of gynecological oncology (NSGO)

Nonepithelial ovarian cancer (NEOC) represents a wide variety of rare tumors. They are often diagnosed at an early stage and have a good prognosis compared to epithelial ovarian cancer. In the Nordic countries, the total annual number of patients diagnosed with ovarian cancer, Fallopian tube cancer or primary peritoneal carcinoma (hereafter ovarian cancer) was 2281 in 2014-2018, of which 3-10% were NEOC. International guidelines for diagnosis, treatment and follow-up have been developed. We present the results of a survey, aiming at clarifying current clinical practice in the Nordic countries. Between 09.2020 and 02.2021 a 33-question electronic survey was distributed to 22 hospitals in Finland, Sweden, Norway, Iceland and Denmark Twenty-one (95,4%) centers completed the survey. A total of 155 annual new NEOC cases treated in the Nordic countries were reported, corresponding to approximately 7% of all ovarian cancer cases. Most centers measured some or all of the recommended biomarkers routinely. Vaginal ultrasound and computed tomography (CT) were the preferred imaging modalities. The majority of centers conducted multidisciplinary team (MDT) meetings. The primary reported treatment was surgery. In 65% of centers, lymph node dissection was only performed in cases with suspicious lymph nodes. Surveillance was usually offered > four years. Despite, the presence of clinical European guidelines, variation in the current clinical practice amongst participating centers adhering to national guidelines was observed. Prospective clinical national research programs are sparse, and an enhanced cooperation in the Nordic countries toward development of a Nordic guideline and database is highly warranted and a prerequisite for future research, preferably in cooperation with the larger international groups.

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.

The Diagnostic Value of Circulating Cell-Free HPV DNA in Plasma from Cervical Cancer Patients

Circulating cell-free HPV DNA (ccfHPV DNA) may serve as a marker for cervical cancer. In this study, we used digital droplet PCR (ddPCR) to detect and quantify ccfHPV DNA in plasma from patients with HPV16- or HPV18-associated cervical cancer. Blood samples from 60 patients diagnosed with cervical cancer (FIGO IA1-IVA) at Aarhus or Odense University Hospital (June 2018 to March 2020) were collected prior to treatment, and patients were subdivided into an early stage (n = 30) and a late-stage subgroup (n = 30) according to disease stage. Furthermore, blood samples from eight women with HPV16- or 18-associated premalignant conditions (CIN3), and 15 healthy controls were collected. ddPCR was used to analyze plasma from all participants. ccfHPV DNA was detected in 19 late-stage patients (63.33%), 3 early stage patients (10.00%), and none of the CIN3 patients or controls. Quantitative evaluation showed significant correlations between ccfHPV DNA level and stage, tumor score, and tumor size. Thus, our results indicate that ccfHPV DNA may not be a useful marker for early detection of cervical cancer. However, for patients with advanced stage cervical cancer, ccfHPV DNA level represents a promising tool to establish tumor burden, making it useful for establishing treatment response and monitoring the disease.

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.