Tine Henrichsen Schnack

Demographic clinical and prognostic characteristics of primary ovarian, peritoneal and tubal adenocarcinomas of serous histology — A prospective comparative study

OBJECTIVES Invasive serous adenocarcinomas may present as primary ovarian (POC), primary fallopian tube (PFC) or primary peritoneal (PPC) carcinomas. Whether they are variants of the same malignancy or develop through different pathways is debated. METHODS Population-based prospectively collected data on POC (n=1443), PPC (n=268) and PFC (n=171) cases was obtained from the Danish Gynecological Cancer Database (2005-2013). Chi-square, Fishers or Wilcoxon-Mann-Whitney test, multivariate logistic regression, Kaplan-Meier and multivariate Cox-regression were used as appropriate. Statistical tests were 2-sided. P-values of <0.05 were considered statistically significant. RESULTS PPC cases were older (P<0.0001), had a later age at menarche (P=0.02), a higher percentage were multi-parous (≥two children vs. no children) OR 1.70 (1.01-2.49) and both PPC and PFC tended to have a higher BMI (>35 vs. >18.5-25) than POC cases. PFC cases were diagnosed in earlier stages (P<0.001). In advanced stages a lower proportion had preoperative carcinosis or ascites, and a higher percentage had macro-radical surgery or lymphadenectomy compared to POC. In contrast, more PPC cases had post-operative carcinosis; whereas a lower proportion had lymphadenectomy or macro-radical surgery compared to POC. PPC had a significantly lower overall survival than POC, HR=1.24 (1.04-1.47). CONCLUSION We found differences in risk pattern profiles among the three groups, especially for PPC. Furthermore, the severity of stage specific disease differed significantly according to location, resulting in a lower overall survival for PPC. These differences warrant further research to determine to what extent PPC is a distinct disease entity.

Risk factors of epithelial ovarian carcinomas among women with endometriosis: a systematic review

The objective of this review was to evaluate the published literature on epidemiologic risk factors for epithelial ovarian cancer among women with a diagnosis of endometriosis.

Demographic Clinical and Prognostic Factors of Primary Ovarian Adenocarcinomas of Serous and Clear Cell Histology-A Comparative Study.

Objective To compare clinical demographic and prognostic factors as well as overall survival in a nationwide cohort of patients diagnosed with ovarian clear cell carcinoma (oCCC) and high grade ovarian serous adenocarcinoma (oSAC) during 2005 to 2013. Materials and Methods Population-based prospectively collected data on oCCC (n = 179) and oSAC (n = 2363) cases were obtained from the Danish Gynecological Cancer Database. &khgr;2, Fischer or Wilcoxon-Mann-Whitney, multivariate logistic regression, univariate Kaplan-Meier, and multivariate Cox regression tests were used. Statistical tests were 2-sided. P values less than 0.05 were considered statistically significant. Results The oCCC cases were significantly younger than oSAC cases. An inverse association between ever smoking and oCCC as compared to oSAC was observed and a significantly higher proportion of oCCC was found to be nulliparous (odds ratio, 0.62; 95% confidence interval, 0.37–0.92). Although more oSAC than oCCC cases diagnosed in stage III or IV were referred to neoadjuvant chemotherapy, a higher proportion of oCCC achieved complete cytoreduction at primary debulking surgery and/or had lymphadenectomy performed; overall survival were poorer among oCCC than oSAC cases in analyses restricted to stages III and IV (odds ratio, 1.87; 95% confidence interval, 1.35–2.61), whereas no difference between early stage oCCC and oSAC was observed. Conclusions The study confirms that demographic features and risk factors differ between oCCC and oSAC cases. Furthermore, our findings confirm that advanced stages of oCCC have a poorer prognosis compared with oSAC probably because of the resistance toward adjuvant chemotherapy. The observed differences highlight the need for subtype-specific research and individualized treatment within ovarian cancer.

Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status

Objectives Women with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according to endometriosis status. Methods Population-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ2 Test, independent-samples t test, logistic regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant. Results Patients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher proportion of them were nulliparous (28% and 31% vs 17% (P = 0.07 and P = 0.09). Accordingly, a significantly higher proportion of women without endometriosis had given birth to more than 1 child. Interestingly, a significantly higher proportion of patients with ovarian endometriosis had pure CCCs (97.8% vs 82.1%; P = 0.001) as compared with patients without endometriosis. Overall survival was poorer among CCC patients with concomitant ovarian endometriosis (hazard ratio, 2.56 [95% confidence interval, 1.29–5.02], in the multivariate analysis. Conclusions Age at CCC diagnosis and parity as well as histology differ between CCC patients with and without concomitant endometriosis. Furthermore, CCC patients with concomitant ovarian endometriosis have a poorer prognosis compared with endometriosis-negative CCC patients. These differences warrant further research to determine whether CCCs with and without concomitant endometriosis develop through distinct pathogenic pathways.

The potential role of infectious agents and pelvic inflammatory disease in ovarian carcinogenesis

BackgroundThe etiological cause of ovarian cancer is poorly understood. It has been theorized that bacterial or viral infection as well as pelvic inflammatory disease could play a role in ovarian carcinogenesis.AimTo review the literature on studies examining the association between ovarian cancer and bacterial or viral infection or pelvic inflammatory disease.MethodsDatabase search through MEDLINE, applying the medical subject headings: “Ovarian neoplasms”, AND “Chlamydia infections”, “Neisseria gonorrhoeae”, “Mycoplasma genitalium”, “Papillomaviridae”, or “pelvic inflammatory disease”. Corresponding searches were performed in EMBASE, and Web of Science. The literature search identified 935 articles of which 40 were eligible for inclusion in this review.ResultsSeven studies examined the association between bacterial infection and ovarian cancer. A single study found a significant association between chlamydial infection and ovarian cancer, while another study identified Mycoplasma genitalium in a large proportion of ovarian cancer cases. The remaining studies found no association. Human papillomavirus detection rates varied from 0 to 67% and were generally higher in the Asian studies than in studies from Western countries. Cytomegalovirus was the only other virus to be detected and was found in 50% of cases in a case-control study. The association between ovarian cancer and pelvic inflammatory disease was examined in seven epidemiological studies, two of which, reported a statistically significant association.ConclusionsData indicate a potential association between pelvic inflammatory disease and ovarian cancer. An association between ovarian cancer and high-risk human papillomavirus genotypes may exist in Asia, whereas an association in Western countries seems unlikely due to the low reported prevalence. Potential carcinogenic bacteria were found, but results were inconsistent, and further research is warranted.

HE4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer.

The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression‐free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance to adjuvant chemotherapy, PFS, and overall survival were analyzed in univariate analyses and in multivariate analyses adjusted for age, performance score, surgical outcome, stage, grade, and histological subtype. Serum HE4 levels predicted chemotherapy resistance, PFS, and overall survival correlated significantly (p < 0.001) in the univariate analyses; but after adjustment in a multivariate model, serum HE4 was insignificant, except in a subgroup analysis of postmenopausal women, where serum HE4 significantly predicted resistance to chemotherapy and progression‐free survival. HE4 tissue protein expression predicted PFS (p = 0.022) and overall survival (p = 0.047) in the univariate analysis, while HE4 tissue protein expression failed to predict these outcomes in the adjusted multivariate analyses. Serum HE4 or HE4 tissue protein expression are not independent factors of chemotherapy resistance or survival in patients with EOC, but serum HE4 might predict chemotherapy resistance and PFS in postmenopausal women.

High-risk HPV is not associated with epithelial ovarian cancer in a Caucasian population

BackgroundHigh-risk human papillomavirus (HPV) has been suspected to play a role in the carcinogenesis of epithelial ovarian cancer (EOC). However, results from previous studies are conflicting. In most of these studies, the number of tissue samples was small. The current study was therefore undertaken to examine the prevalence of high-risk HPV DNA in EOC in a large series of patients.MethodFormalin-fixed, paraffin-imbedded tumor tissue samples from 198 cases consecutively included in the Danish Pelvic Mass Study were analyzed. The material included 163 serous adenocarcinomas, 15 endometrioid adenocarcinomas, 11 mucinous adenocarcinomas and nine clear-cell carcinomas. Genotyping for high-risk HPV DNA was performed by real-time Polymerase chain reaction (PCR) using an in-house TaqMan singleplex assay targeting the E6/E7 region of the HPV 16 and 18 genomes. Additionally, 20 random samples without HPV 16 and/or 18 infections were reanalyzed for HPV subtypes 31, 33, 35, 39, 45, 51 and 52.ResultsThe quality criteria were fulfilled in 191 samples. HPV 18 DNA was detected in one sample only, while the rest tested negative. The subgroup analysis for seven additional high-risk HPV subtypes was also negative.ConclusionsOnly one in 191 samples was positive for HPV DNA. We therefore conclude that high risk HPV is unlikely to be associated with EOC in a Caucasian population. Future studies should focus on other microorganisms as possible etiological factors in EOC carcinogenesis.

Assessing patient reported quality of life outcomes in vulva cancer patients: a systematic literature review

Objectives Vulva cancer (VC) treatment carries a high risk of severe late effects that may have a negative impact on quality of life (QoL). Patient-reported outcome measures (PROMs) are increasingly used when evaluating disease- and treatment-specific effects. However, the adequacy of measures used to assess sequelae and QoL in VC remains unclear. The aims of the present study were to evaluate disease- and treatment-related effects as measured by PROMs in VC patients and to identify available VC-specific PROMs. Methods/Materials A systematic literature search from 1990 to 2016 was performed. The inclusion criterion was report of disease- and treatment-related effects in VC patients using PROMs in the assessment. Methodological and reporting quality was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. This systematic review was performed as part of phase 1 of the development of a European Organisation for Research and Treatment of Cancer QoL questionnaire for VC patients. Results The search revealed 2299 relevant hits, with 11 articles extracted including a total of 535 women with VC; no randomized controlled trials were identified. The selected studies exhibited great heterogeneity in terms of PROMs use. Twenty-one different instruments assessed QoL. Most of the questionnaires were generic. Different issues (sexuality, lymphedema, body image, urinary and bowel function, vulva-specific symptoms) were reported as potentially important, but the results were not systematically collected. Only one VC-specific questionnaire was identified but did not allow for assessment and reporting on a scale level. Conclusions Vulva cancer treatment is associated with considerable morbidity deteriorating QoL. To date, there is no validated PROM available that provides adequate coverage of VC-related issues. The study confirms the need for a VC-specific QoL instrument with sensitive scales that allows for broad cross-cultural application for use in clinical trials.

Impact of residual disease on overall survival in patients with FIGO stage IIIB‐IIIC vs. stage IV epithelial ovarian cancer after primary surgery

The objective of this study was to determine the impact of intra‐abdominal residual disease size, type (carcinomatosis, tumor mass or both), and location (upper/lower abdominal/both) on overall survival in women with Federation of Gynecology and Obstetrics (FIGO) stage IIIB‐IIIC vs stage IV epithelial ovarian cancer who underwent primary debulking surgery.

Classification of Ovarian Cancer Surgery Facilitates Treatment Decisions in a Gynecological Multidisciplinary Team

Objective Proper planning of intervention and care of ovarian cancer surgery is of outmost importance and involves a wide range of personnel at the departments involved. The aim of this study is to evaluate the introduction of an ovarian surgery classification (COVA) system for facilitating multidisciplinary team (MDT) decisions. Materials and Methods Four hundred eighteen women diagnosed with ovarian cancers (n = 351) or borderline tumors (n = 66) were selected for primary debulking surgery from January 2008 to July 2013. At an MDT meeting, women were allocated into 3 groups named “pre-COVA” 1 to 3 classifying the expected extent of the primary surgery and need for postoperative care. On the basis of the operative procedures performed, women were allocated into 1 of the 3 corresponding COVA 1 to 3 groups. The outcome measure was the predictive value of the pre-COVA score compared with the actual COVA performed. Results The MDT meeting allocated 213 women (51%) to pre-COVA 1, 136 (33%) to pre-COVA 2, and 52 (12%) to pre-COVA 3. At the end of surgery, 168 (40%) were classified as COVA 1, 158 (38%) were classified as COVA 2, and 28 (7%) were classified as COVA 3. Traced individually, 212 (51%) patients were correctly preclassified at the MDT meeting and distributed into 110 (52%) COVA 1, 71 (52%) COVA 2, and 17 (32%) COVA 3. Analyzing the subgroup of patients with cancer, 164 (47%) were correctly preclassified. Regarding the International Federation of Gynecology and Obstetrics (FIGO) stages, the pre-COVA classification predicted the actual COVA group in 79 (49%) FIGO stages I to IIIB and in 85 (45%) FIGO stages IIIC to IV. Conclusions The COVA classification system is a simple and useful tool in the MDT setting where specialists make treatment decisions based on advanced technology. The use of pre-COVA classification facilitates well-organized patient care–relevant procedures to be undertaken. Pre-COVA accurately predicts the final COVA in 51% classified women.