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ObjectivesTime trends on the incidence and characteristics of invasive vulvar cancer in Germany have so far been studied in few local population- and hospital based tumor registries. We aimed to provide an overview on recent developments of vulvar cancer in Germany, using population-based cancer registry data.MethodsWe analyzed the data on vulvar cancer of eight population-based German cancer registries for the period 1999-2011. ICD-10 codes and ICD-O-3 morphology codes were used to select site and histologic types. The annual percentage change was calculated on age-adjusted incidence rates with a joinpoint regression model.ResultsA total of 12,711 registered cases of invasive carcinoma of the vulva were included in the analyses, hereof were 12,205 of squamous cell origin. Age-standardized incidence rates of vulvar cancer annually increased by 6.7% (95% confidence limits: 5.6-7.9) from 1.7 per 100,000 women in 1999 to 3.6 per 100,000 women in 2011. An increase was observed among women of all ages, and especially between 30 and 69 years of age.ConclusionThe annual incidence of invasive carcinoma of the vulva nearly doubled in the past decade in Germany, considerably exceeding the rates observed in other Western European countries. A combination of changes in risk factors, and documentation practice might have contributed to the observed substantial increase in vulvar cancer incidence.

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ObjectiveWe examined a large series of biopsy-proven invasive cervical cancers with surgical staging and HPV re-testing to estimate the relevance of HPV-negative cervical cancers in a Caucasian population.MethodsWe prospectively collected smears from 371 patients with a biopsy-proven diagnosis of cervical cancer for HC2 testing of high-risk HPV (HR-HPV). In HC2-negative cases, smears and paraffin embedded tissue blocks underwent additional HPV genotyping.ResultsHC2 tests showed 31/371 cases (8.8%) had negative findings. Surgical staging showed that 21/31 HC2-negative cases (68%) were not cervical cancer. Overall, 340/350 cases of primary cervical cancer confirmed by surgical staging tested HC2 positive (97.2%). Non-high-risk HPV subtypes were detected in five cases (one HPV-53, one HPV-70, and three HPV-73) and high-risk subtypes in four patients with HC2-negative cervical cancer (two HPV 16 and two HPV-18). The remaining case, a primary undifferentiated carcinoma of the uterine cervix, tested negative for HPV-DNA with all tests.ConclusionsThe main explanation for HPV-negative cervical cancer was a false diagnosis, followed by cancers associated with non-HR-HPV types, and false-negative HR-HPV results. Truly HPV negative seem to be very rare in Caucasian populations. Retrospective analyses without surgical staging may overestimate the proportion of HPV negative cervical cancers.

We evaluated compliance with human papillomavirus (HPV) testing and risk-adapted patient pathways and monitored changes in high-grade cervical disease during long-term follow-up. Women aged >30 years attending routine screening for cervical cancer were managed according to results from first-round screening tests (cytology and high-risk HPV; Hybrid Capture 2). Between February 2006 and January 2011, 19,795 of 19,947 women agreed to participate, of whom 4,067 proceeded to a second screening round 5 years after recruitment. Predefined endpoints were compliance, grade 3 cervical intraepithelial neoplasia or cancer (CIN3+), new HPV infection, HPV persistence and abnormal smears in round 2. A total of 765 of 19,795 women (3.9%) in round 1 and 41 of 4,067 (1.0%) in round 2 were referred for colposcopy. Compliance rates with colposcopy were 93.1 and 92.7%, respectively, while histological assessment was performed in 680 of 712 (95.5%) and 36 of 38 (94.7%), respectively. CIN3+ rates were 172 of 19,795 (0.87%; 95% confidence intervals: 0.7-1.0) in round 1 and 2 of 4,064 (0.05%; 95% confidence intervals: 0.006-0.2) in round 2; the difference was statistically significant (Fisher's exact test, p<0.001). After 5 years, the incidence of new HPV infection was 124 of 3,906 (3.2%) and HPV persistence was observed in 22 of 161 (13.7%). Locally organised HPV/cytology co-testing is feasible and acceptable to women. Risk-adapted management rapidly detected a high rate of prevalent CIN3+, while the subsequent long-term risk of new high-grade cervical disease was surprisingly low. It remains unclear if this phenomenon is explained by CIN3 mostly occurring early in life or by modifying the natural course of HPV infection with colposcopy and histological assessment.