OBJECTIVE: Human papillomavirus (HPV) is a necessary cause for cervical cancer, and it has been associated with vulvar and vaginal cancer and vulvar (VIN) and vaginal (VaIN) and anal (AIN) intraepithelial neoplasia. We assessed the prevalence of HPV (and the types) to estimate the possible effect of a HPV vaccine on lower genital tract disease prevention. METHODS: Two hundred fifty-eight samples of VIN, VaIN, AIN, and vulvar cancer from 241 women were included in the study. The diagnosis of surgical samples was made using published histomorphologic criteria. The DNA was extracted for HPV detection and typed using polymerase chain reaction and sequencing. RESULTS: The analyses were performed on 210 intraepithelial neoplasia samples (VIN2/3, VaIN2/3, AIN2/3) and 48 vulvar carcinoma samples. Human papillomavirus DNA was detected in 92%, 91%, 89%, and 60% of the VIN, VaIN, AIN, and vulvar carcinoma samples, respectively. High-risk HPV types 16 or 18 were detected in 76%, 64%, 81%, and 42% of the VIN2/3, VaIN2/3, AIN, and vulvar carcinoma samples. Women with HPV-positive samples were younger than those with HPV-negative samples (46 years compared with 55 years and 51 years compared with 61 years, for the VIN2/3 and vulvar carcinoma samples, respectively). Human papillomavirus–positive vulvar carcinoma was more frequent in women aged younger than 56 years (77%), than in those aged 56 years or older (41%). CONCLUSION: Based on the data obtained in this study, widely-implemented prophylactic HPV vaccination could make an important contribution to the reduction of the risk for cervical cancer and could also prevent about half the vulvar carcinomas in younger women and about two thirds of the intraepithelial lesions in the lower genital tract. LEVEL OF EVIDENCE: II-3

Background/purpose: The incidence and clinical course of high-grade cervical intraepithelial lesions (CIN 2/3) are age dependent. In CIN 3, the recommended treatment is conization, which increases the risk of cervical insufficiency or premature deliveries. But data concerning spontaneous regression of CIN 3 are rare. Methods: Between 2007 and 2017, we identified 156 women under the age of 25 with CIN 2 (23%) or CIN 3 (77%), who had a consultation and were treated at the Colposcopy Unit, Hospital of Düsseldorf, Germany. This is a retrospective cohort study. These patients had colposcopical follow-ups every 4–6 months. Moreover, we analyzed various parameters to predict regression of cervical lesions in this age group. Results: Patients diagnosed with CIN 2 showed regression in 88% (n = 30) and women with CIN 3 had a regression rate of 29% (n = 34). Complete regression was observed in 86.7% of CIN 2 and 47.1% of CIN3. Mean time to regression was 21 M (months) [2–70 M]. 70.9% of the patients were treated by surgery (LEEP) after persistence or progression. We identified several predictors for regression of CIN 2/3 in young women: the regression rate of CIN2 is significantly higher than CIN 3 (p < 0.001). Clearance of HPV infections had significantly higher rates of regression compared to persisting HPV infections (p < 0.001). HPV-vaccinated women showed significantly higher regression rates (p = 0.009). Conclusions: These data show that an expectative close follow-up in women with CIN 3 younger than 25 is possible with regression rates of 29% also for CIN 3. Especially in women who were HPV vaccinated and those who cleared their HPV infection. A frequent colposcopical follow-up every 3–4 months is important for CIN 3 and every 6 months for CIN 2.

Objective The incidence of vulvar squamous cell carcinomas located between the clitoris and urethra in young women is rising in distinct geographic regions, but characteristics of the tumors indicating certain carcinogenic mechanisms are unknown. The present study aimed at characterizing these vulvar cancers for their human papillomavirus (HPV), p16^INK4a, and p53 status, revealing potential pathways of carcinogenesis. Materials and Methods Squamous cell vulvar cancers of the anterior fourchette were retrospectively collected from 8 German hospitals, with additional squamous cell cancers located at other sites of the vulva from 2 of the hospitals. All tumors were analyzed for HPV DNA by polymerase chain reaction and for p16^INK4a and p53 expression by immunohistochemistry. Results Potentially HPV-associated tumors (HPV and p16^INK4a positive, 21.4% [27/126] of the anterior fourchette and 27.7% [13/47] from other locations), p53-overexpressing tumors (35.7% [45/126] and 29.8% [14/47]), and a third group (HPV/p16 negative/p53 not overexpressed, 42.9% [54/126] and 42.6% [20/47]) were observed among tumors from the anterior fourchette as well as among vulvar cancers from other locations. Women with vulvar cancers of the anterior fourchette were of young age irrespective of the HPV/p16^INK4a/p53 status. Conclusions Different types of vulvar cancers can be found in squamous cell tumors of the anterior fourchette, similar to the finding in vulvar cancers from other locations and to what has previously been reported for vulvar squamous cell carcinomas in general.

Cervical intraepithelial neoplasia (CIN) grade 2/3 has a high spontaneous regression rate, especially among women ≤29 years of age. To reduce overtreatment, reliable prognostic biomarkers would be helpful. The main aim of this study was to analyze the negative predictive value of the methylation marker panel GynTect^® for lesion regression. In this prospective, multicenter, longitudinal observational proof-of-concept study, women aged ≤29 years with histologically confirmed CIN2 (n = 24) or CIN3 (n = 36) were closely monitored without treatment for up to 24 or 12 months, respectively. The outcome was either regression, persistence, or progression of the lesion. For each patient, a single baseline sample (V0) for cytology, hrHPV detection and methylation analysis was taken. In a primary analysis, the negative predictive value (NPV) of a GynTect^®-negative test result at V0 for regression was determined. We tested the null hypothesis NPV ≤ 70% against the alternative hypothesis NPV ≥ 90%. Twelve of the eighteen GynTect^®-negative CIN2 patients showed regression (NPV = 67%, 90% CI 44–85%, p = 0.53). Of the 27 GynTect^®-negative CIN3 lesions, 15 regressed (NPV = 56%, 90% CI 38–72%, p = 0.92). Although the majority of GynTect^®-negative lesions regressed, the postulated NPV of ≥90% was not observed. Thus, the clinical relevance for an implementation of the GynTect^® assay for patients undergoing watchful waiting remains questionable. Further studies with longer observation periods should be undertaken.