(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is challenging; abnormal cytology and positive HPV tests are usually the first signs, but published data on their accuracy for detecting it are rare and contradictory. The aim of this study is to compare the results of hrHPV and cytology co-testing with the histological findings of the vagina. (2) Methods: In the certified Dysplasia Unit at Erlangen University Hospital, cytology and HPV samples from the uterine cervix or vaginal wall after hysterectomy were obtained between 2015 and 2023 and correlated with histological findings in biopsies from the vaginal wall. Women without vaginal biopsy findings or concomitant cervical disease were excluded. (3) Results: In all, 279 colposcopies in 209 women were included. The histological results were: benign (n = 86), VaIN I/vLSIL (n = 116), VaIN II/vHSIL (n = 41), VaIN III/vHSIL (n = 33), and carcinoma (n = 3). Accuracy for detecting VaIN was higher in women with previous hysterectomies. Positive HPV testing during colposcopy increased the likelihood for VaIN II/III/vHSIL threefold. The detection rate for VaIN III/vHSIL was 50% after hysterectomy and 36.4% without hysterectomy. (4) Conclusions: Women with risk factors for VaIN, including HPV-16 infection or prior HPV-related disease, need careful work-up of the entire vaginal wall. Hysterectomy for HPV-related disease and a history of cervical intraepithelial neoplasia (CIN) also increased the risk for VaIN II/III/vHSIL.
Keywords: colposcopy; cytology; human papillomavirus; hysterectomy; pap smear; vaginal cancer; vaginal intraepithelial neoplasia (VaIN).