Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial).

BACKGROUND: This study aimed to describe the treatment strategies and outcomes for women with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer (OC). METHODS: This observational study collected real-world medical record data from eight Western countries on the diagnostic workup, clinical outcomes, and treatment of adult women with newly diagnosed advanced (Stage III-IV) high-grade serous or endometrioid OC. Patients were selected backward in time from April 1, 2018 (the index date), with a target of 120 patients set per country, followed for ≥20 months. RESULTS: Of the 1119 women included, 66.9% had Stage III disease, 11.7% had a deleterious BRCA mutation, and 26.6% received bevacizumab; 40.8% and 39.3% underwent primary debulking surgery (PDS) and interval debulking surgery (IDS), respectively. Of the patients who underwent PDS, 55.5% had no visible residual disease (VRD); 63.9% of the IDS patients had no VRD. According to physician-assessed responses (at the first assessment after diagnosis and treatment), 53.2% of the total population had a complete response and 25.7% had a partial response to first-line chemotherapy after surgery. After ≥20 months of follow-up, 32.9% of the patients were disease-free, 46.4% had progressive disease, and 20.6% had died. Bevacizumab use had a significant positive effect on overall survival (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91; p = .01). A deleterious BRCA status had a significant positive effect on progression-free survival (HR, 0.60; 95% CI, 0.41-0.84; p < .01). CONCLUSIONS: Women with advanced high-grade serous or endometrioid OC have a poor prognosis. Bevacizumab use and a deleterious BRCA status were found to improve survival in this real-world population. LAY SUMMARY: Patients with advanced (Stage III or IV) ovarian cancer (OC) have a poor prognosis. The standard treatment options of surgery and chemotherapy extend life beyond diagnosis for 5 years or more in only approximately 45% of patients. This study was aimed at describing the standard of care in eight Western countries and estimating how many patients who are diagnosed with high-grade serous or endometrioid OC could potentially be eligible for first-line poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) maintenance therapy. The results highlight the poor prognosis for these patients and suggest that a significant proportion (79%) would potentially be eligible for first-line PARPi maintenance treatment.

Preoperative predictors of inguinal lymph node metastases in vulvar cancer - A nationwide study.

BACKGROUND: A combination of tumour size, differentiation grade and location may identify a group of vulvar squamous cell cancer (VSCC) patients with a very low risk of inguinal lymph node metastasis. We aim to examine these findings in a large national cohort of VSCC patients. MATERIALS AND METHODS: Population based prospective data on VSCC patients treated with vulvectomy and primary groin surgery was obtained from the Danish Gynaecological Cancer Database. Univariate chi-square and multivariate logistic regression analysis were used. Statistical tests were 2-sided. P-values of <0.05 were considered statistically significant. RESULTS: In all, 388 VSCC patients were identified. Of these 264 (63.3%) were node negative and 121 (36.7%) node positive. Increasing tumour size (diameter ≤ 2 cm vs. > 2 to 4 cm), grade (1 vs. 2-3) and location of tumour to clitoris were all associated with a significantly increased risk of inguinal lymph node metastasis OR 2.81(95% CI 1.52-5.20), OR 3.19 (95% CI 1.77-5.74) and OR 2.74 (95% CI 1.56-5.20), respectively. Previous vulvar disease was not associated with lymph node metastasis. No lymph node metastasis was demonstrated in patients with grade 1 tumours, tumour size less than 2 cm and located outside the clitoris area (n = 51). CONCLUSIONS: VSCC patients with grade 1 tumours, ≤ 2 cm and without clitoral involvement have a very low risk of inguinal lymph node metastasis. These patients may be spared inguinal lymph node staging to decrease operating time and peri- and postoperative morbidity in the future. However, studies validating our findings are needed.

Assessment of recurrence rate and risk factors of relapse in stage in IA vulvar carcinoma.

OBJECTIVE: To evaluate recurrence rates and risk factors of relapse in stage IA vulvar squamous cell carcinoma (VSCC) patients. MATERIAL AND METHODS: Population-based prospectively collected data on stage IA VSCC was retrieved through the Danish Gynecological Cancer Database (DGCD) during 2011-2017. A central pathology review was performed on tumors from women with recurrent disease. RESULTS: 62 women diagnosed and treated for stage IA VSCC were identified. Nine (14.5%) of the included cases relapsed within the observation period. The recurrences were in the vulva, groins or both in 5 (8.1%), 3 (4.8%) and 1 (1.6%) of the women, respectively. At central pathology review, including all recurrent cases (n = 9), 5 out of 21 reviewed patients were upstaged to stage IB due to depth of invasion >1 mm and two were downstaged to Carcinoma in situ. Two of the upstaged women developed an isolated groin recurrence and one an isolated vulvar relapse. After exclusion of the seven cases the overall recurrence rate decreased to 10.9% (n = 6). Among these cases (n = 55) resection margin <8 mm and tumor size were associated with cancer recurrence. CONCLUSION: Pathological assessment of stage IA VSCC (depth of invasion ≤1 mm) may be difficult. This may result in under-staging, which impact the choice of treatment and possibly the prognosis. This suggests a need for further clarification of the FIGO measurement and may require a more radical approach when it comes to treatment and groin exploration in stage IA VSCC. Resection margins <8 mm and tumor size were associated with relapse of the disease.

Incidence, treatment, and survival trends in older versus younger women with epithelial ovarian cancer from 2005 to 2018: A nationwide Danish study.

OBJECTIVE: To examine clinical trends in Denmark for younger and older epithelial ovarian cancer (EOC) patients, focusing on incidence, treatment, and survival changes. METHODS: We included a nationwide cohort diagnosed with EOC from 2005 to 2018. We described age-standardized incidence, surgical patterns, residual disease trends, and cancer-specific survival stratified by age (<70 and ≥ 70 years), stage, and period (2005-09, 2010-13, 2014-18). RESULTS: We included 7522 patients. The incidence decreased from 16.3 (2005) to 11.4 (2018) per 100,000 woman-years, driven by the younger cohort. While the proportion of patients with stage IIIC-IV disease undergoing primary debulking surgery (PDS) decreased, the proportion of patients having interval debulking surgery (IDS) and no debulking surgery increased significantly. In 2014-18, 36% and 24% had PDS for younger and older patients, respectively, compared to 72% and 62% in 2005-09. In both age cohorts, the proportion of patients debulked to no residual disease increased significantly among patients with stage IIIC-IV and in the total cohort. Two-year cancer-specific survival increased from 75% (2005-09) to 84% (2014-18) for younger patients and from 53% to 66% for older patients. After adjusting for potential confounders, age ≥ 70 was associated with a 1.4-fold increased risk of cancer-specific death (95% confidence interval: 1.2,1.5). CONCLUSIONS: The proportion of patients with advanced EOC not undergoing PDS or IDS increased significantly. During the same period, patients debulked to no residual disease, and cancer-specific survival increased. However, a survival gap in favor of the younger patients remains after adjusting for potential confounders.

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

INTRODUCTION: It 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 METHODS: We 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. RESULTS: In 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. CONCLUSIONS: Our 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.

Recurrence and survival rates in node negative patients after sentinel node biopsy for early-stage vulva cancer - A nationwide study.

OBJECTIVE: The sentinel node (SN) procedure is adopted in selected patients with early-stage vulva cancer (VC) in Denmark. Due to the low incidence of VC, large population-based studies on the safety of SN outside multicenter clinical trials are lacking. The current study evaluated the risk of recurrence and survival in SN- negative VC patients. METHODS: Nationwide data was collected and registered prospectively in the Danish Gynecologic Cancer Database from January 2011 to July 2017. Patients with clinically stage IB-II unifocal vulva squamous cell carcinoma, tumor <4 cm and no clinically suspicious groin nodes or distant metastases, who underwent SN-procedure, were included. RESULTS: The SN-procedure was performed in 286 patients, of these 190 (66.4%) patients were SN-negative. Twenty-three of the 190 SN-negative patients (12.1%) had one or more recurrences during a median follow-up of 30 months (range 1-83). Four patients (2.1%) had an isolated groin recurrence identified from 5 to 17 months after primary surgery. Fourteen patients (7.4%) experienced a local recurrence in vulva, 1 patient (0.5%) had a recurrence in the vulva and the groin and 4 patients (2.1%) had distant recurrences. The 3-year overall (OS) and disease-specific survival (DSS) for SN-negative patients was 84% and 93%, respectively. The 3-year OS for patients with recurrent disease was 58%. CONCLUSIONS: This is the largest prospective nationwide study on SN-procedure in vulva cancer. The study confirms the safety of the SN-procedure in selected early-stage VC patients with a low isolated groin recurrence rate and a good DSS.

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.

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.

A novel index for preoperative, non-invasive prediction of macro-radical primary surgery in patients with stage IIIC-IV ovarian cancer-a part of the Danish prospective pelvic mass study.

The purpose of this study was to develop a novel index for preoperative, non-invasive prediction of complete primary cytoreduction in patients with FIGO stage IIIC-IV epithelial ovarian cancer. Prospectively collected clinical data was registered in the Danish Gynecologic Cancer Database. Blood samples were collected within 14 days of surgery and stored by the Danish CancerBiobank. Serum human epididymis protein 4 (HE4), serum cancer antigen 125 (CA125), age, performance status, and presence/absence of ascites at ultrasonography were evaluated individually and combined to predict complete tumor removal. One hundred fifty patients with advanced epithelial ovarian cancer were treated with primary debulking surgery (PDS). Complete PDS was achieved in 41 cases (27 %). The receiver operating characteristic curves demonstrated an area under the curve of 0.785 for HE4, 0.678 for CA125, and 0.688 for age. The multivariate model (Cancer Ovarii Non-invasive Assessment of Treatment Strategy (CONATS) index), consisting of HE4, age, and performance status, demonstrated an AUC of 0.853. According to the Danish indicator level, macro-radical PDS should be achieved in 60 % of patients admitted to primary surgery (positive predictive value of 60 %), resulting in a negative predictive value of 87.5 %, sensitivity of 68.3 %, specificity of 83.5 %, and cutoff of 0.63 for the CONATS index. Non-invasive prediction of complete PDS is possible with the CONATS index. The CONATS index is meant as a supplement to the standard preoperative evaluation of each patient. Evaluation of the CONATS index combined with radiological and/or laparoscopic findings may improve the assessment of the optimal treatment strategy in patients with advanced epithelial ovarian cancer.

Prognostic impact of molecular profiles and molecular signatures in clear cell ovarian cancer.

OBJECTIVE: Ovarian Clear cell carcinomas (OCCC) are characterized by low response to chemotherapy and a poor prognosis in advanced stages. Several studies have demonstrated that OCCC are heterogenous entities. We have earlier identified four molecular profiles based on the mutational status of ARID1A and PIK3CA. In this study we aimed to examine the association between molecular profiles, Tumor Mutational Burden (TMB), and molecular signatures with the clinical outcome in OCCC METHODS: We identified 55 OCCC cases with corresponding data and biological tissue samples in the Danish Gynecological Cancer Database during 2005-2016. Mutational profiling and TMB were performed using the Oncomine Tumor Mutational Load Assay. Chi-square and Cox regression analyses were used. P-values < 0.05 were considered statistically significant. RESULTS: Mutations in the PIK3CA gene (p=0.04) and low TMB (p=0.05) were associated with disease progression. In multivariate analyses adjusted for stage, patients with tumor mutations in the ARID1A and/or PIK3CA genes had a significantly impaired Progression Free Survival (PFS) and Overall Survival (OS) compared to patients who were wildtype ARID1A and PIK3CA (undetermined subgroup) (HR= 5.42 and HR= 2.77, respectively). High TMB status was associated with an improved PFS (HR= 0.36) and OS (HR= 0.46). A trend towards an improved PFS in patients with APOBEC enrichment was observed (HR 0.45). CONCLUSION: TMB-High was associated with decreased risk of progression and with an improved PFS and OS. Furthermore, OCCC with mutations in either ARID1A and/or PIK3CA genes had a significantly impaired prognosis compared to the undetermined subgroup in stage adjusted analyses.

Days alive and out of hospital after surgical treatment of epithelial ovarian cancer: A Danish nationwide cohort study.

OBJECTIVE: Days alive and out of hospital (DAOH) is a validated outcome measure in perioperative trials integrating information on primary hospitalization, readmissions, and mortality. It is negatively associated with advanced age. However, DAOH has not been described for surgical treatment of epithelial ovarian cancer (EOC), primarily diagnosed in older patients. METHODS: We conducted a Danish nationwide cohort study including patients undergoing debulking surgery for EOC from 2013 to 2018. DAOH was explored for 30 (DAOH30), 90 (DAOH90), and 180 (DAOH180) postoperative days in younger (<70 years) and older (≥70 years) patients with advanced-stage disease stratified by surgical modality (primary (PDS) or interval debulking surgery (IDS)). We examined the associations between patient- and surgical outcomes and low or high DAOH30. RESULTS: Overall, 1168 patients had stage IIIC-IV disease and underwent debulking surgery. DAOH30 was 22 days [interquartile range (IQR): 18, 25] and 23 days [IQR: 18, 25] for younger and older patients treated with PDS, respectively. For IDS, DAOH30 was 25 days [IQR: 22, 26] for younger and 25 days[IQR: 21, 26] for older patients. We found no significant differences between age cohorts regarding DAOH30, DAOH90, and DAOH180. Low DAOH30 was associated with poor performance status, PDS, extensive surgery, and long duration of surgery in adjusted analysis. CONCLUSIONS: DAOH did not differ significantly between age cohorts. Surgical rather than patient-related factors were associated with low DAOH30. Our results likely reflect a high selection of fit older patients for surgery, reducing the patient-related differences between younger and older patients receiving surgical treatment.

Impact of surgery and chemotherapy timing on outcomes in older versus younger epithelial ovarian cancer patients: A nationwide Danish cohort study.

INTRODUCTION: To explore differences in surgical complexity, chemotherapy administration, and treatment delays between younger and older Danish patients with epithelial ovarian cancer (EOC). MATERIALS AND METHODS: We included a nationwide cohort diagnosed with EOC from 2013 to 2018. We described surgical complexity and outcomes, the extent of chemotherapy and treatment delays stratified by age (<70 and ≥ 70 years), and surgical modality (primary, interval, or no debulking surgery). RESULTS: In total, we included 2946 patients. For patients with advanced-stage disease, 52% of the older patients versus 25% of the younger patients did not undergo primary debulking surgery (PDS) or interval debulking surgery (IDS). For patients undergoing PDS or IDS, older patients underwent less extensive surgery and more often had residual disease after surgery >0 cm compared to younger patients. Furthermore, older patients were less often treated with chemotherapy. Older patients had PDS later than younger. We did not find any differences between age groups concerning treatment delays. Two-year cancer-specific survival differed significantly between age groups regardless of curatively intended treatment. DISCUSSION: This study demonstrates that older patients are treated less actively concerning surgical and oncological treatment than younger patients, leading to worse cancer-specific survival. Older patients do not experience more treatment delays than younger ones.

Danish translation, cross-cultural adaptation, and electronic migration of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project Endometriosis Patient Questionnaire.

Objectives: This study aims to translate and cross-culturally adapt the standard version of the World Endometriosis Research Foundation (WERF) EPHect Endometriosis Patient Questionnaire (EPQ) into Danish and to ensure equivalence of a Danish electronic version. Methods: The translation, cultural adaption, and electronic migration followed recommendations from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the Critical Path Institute. Ten women with endometriosis were enrolled for cognitive debriefing of the paper version (pEPQ) after translation and back translation. The questionnaire was then migrated into an electronic version (eEPQ) and subsequently tested for usability and measurement equivalence by five women with endometriosis. Results: Cross-cultural alterations were needed for medical terms, response options for ethnicity, the educational system, and measurement units. Thirteen questions were altered after back translation, while 21 underwent minor changes after cognitive debriefing. After testing the eEPQ, 13 questions were altered. Questions tested for measurement equivalence across the two modes of administration were found comparable. The median time-to-complete the pEPQ and eEPQ was 62 min (range: 29-110) and 63 min (range: 31-88), respectively. General comments included the questionnaire being relevant but long and repetitive. Conclusions: We find the the Danish pEPQ and eEPQ similar and comparable to the original English instrument. However, attention must be drawn to questions regarding measurement units, ethnicity, and educational systems before cross-country comparison. The Danish pEPQ and eEPQ are suitable for obtaining subjective data on women with endometriosis.

Potential Targeted Therapies in Ovarian Cancer.

BACKGROUND: We aimed to identify somatic pathogenic and likely pathogenic mutations using next-generation sequencing (NGS). The mutational findings were held against clinically well-described data to identify potential targeted therapies in Danish patients diagnosed with high-grade serous ovarian cancer (HGSC). METHODS: We characterized the mutational profile of 128 HGSC patients. Clinical data were obtained from the Danish Gynecological Database and tissue samples were collected through the Danish CancerBiobank. DNA was analyzed using NGS. RESULTS: 47 (37%) patients were platinum-sensitive, 32 (25%) partially platinum-sensitive, 35 (27%) platinum-resistant, and three (2%) platinum-refractory, while 11 (9%) patients did not receive chemotherapy. Overall, 27 (21%) had known druggable targets. Twelve (26%) platinum-sensitive patients had druggable targets for PARP inhibitors: one for tyrosine kinase inhibitors and one for immunotherapy treatment. Eight (25%) partially platinum-sensitive patients had druggable targets: seven were eligible for PARP inhibitors and one was potentially eligible for alpesilib and hormone therapy. Seven (20%) platinum-resistant patients had druggable targets: six (86%) were potentially eligible for PARP inhibitors, one for immunotherapy, and one for erdafitinib. CONCLUSIONS: PARP inhibitors are the most frequent potential targeted therapy in HGSC. However, other targeted therapies remain relevant for investigation according to our mutational findings.

The prevalence of EBV and CMV DNA in epithelial ovarian cancer.

BACKGROUND: The underlying cause of epithelial ovarian cancer (EOC) is unknown. It has been theorized that infectious agents could contribute to ovarian tumorigenesis. OBJECTIVE: To investigate the potential role of oncogenic viral infection in EOC, we examined the prevalence of Epstein-Barr Virus (EBV) DNA and cytomegalovirus (CMV) DNA in EOC tissue samples. METHODS: Formalin-fixed, paraffin-imbedded (FFPE) tumor tissue samples from 198 patients included in the Danish Pelvic Mass Study were studied: 163 with serous adenocarcinomas, 15 with endometrioid adenocarcinomas, 11 with mucinous adenocarcinomas, and nine with clear-cell carcinomas. For controls in the EBV analysis, we used 176 tissue samples from patients diagnosed with benign mucinous cystadenomas. EBV and CMV genotyping was performed by real-time polymerase chain reaction with CMV and EBV CE-IVD approved kits. In-situ hybridization (ISH) was performed on the EBV positive samples. RESULTS: Sufficient DNA material was obtained in 191 and 174 tissue samples from cases and controls, respectively. Ten of 191 case samples (5.2%) and one of 174 control samples (0.5%) were positive for EBV DNA (P value = 0.011). CMV DNA was detected in only one case sample (0.5%). ISH confirmed that three of the samples were of stromal origin, while the remaining seven tested negative for EBV. CONCLUSIONS: This study is the first to demonstrate a higher prevalence of EBV DNA in tissue samples from patients with EOC than in a benign control group. However, the cellular origin of seven of the samples could not be determined by ISH analysis. Our study did not support an association between CMV and EOC.

[Workup, treatment and follow-up of vulva cancer].

This review summarises the current guidelines for vulva cancer in Denmark. Vulva cancer is a rare disease. The diagnosis is often delayed, which results in large tumours and regional spread. The most important prognostic factor is inguinal lymph node metastases. Staging and treatment is centralised to two hospitals. Primary treatment is wide local excision combined with removal of either inguinal sentinel nodes or lymphadenectomy. Treatment is associated with considerable morbidity, and supportive care is often necessary. Local curable recurrences are common. Relapses in the groin are associated with a poor prognosis. Thus, long term follow-up is essential. *) On behalf of Dansk Gynækologisk Cancer Gruppe for vulvacancer.

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

BACKGROUND: The 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. AIM: To review the literature on studies examining the association between ovarian cancer and bacterial or viral infection or pelvic inflammatory disease. METHODS: Database 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. RESULTS: Seven 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. CONCLUSIONS: Data 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.

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

BACKGROUND: High-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. METHOD: Formalin-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. RESULTS: The 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. CONCLUSIONS: Only 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.