# Vaginal Intraepithelial Neoplasia (VaIN) after Hysterectomy Is Strongly Associated with Persistent HR-HPV Infection

## TL;DR

This study finds that high-grade vaginal intraepithelial neoplasia after hysterectomy is strongly linked to persistent high-risk HPV infection, especially genotype 16.

## Contribution

The study identifies persistent HR-HPV infection as a key risk factor for VaIN after hysterectomy, rather than the surgery itself.

## Key findings

- High-grade VaIN occurred in 4.7% of women after hysterectomy, all with persistent HPV infection.
- Women with a history of CIN3 had an eight-fold higher risk of developing high-grade VaIN.
- HPV genotype 16 was the most frequently detected in VaIN cases.

## Abstract

VaIN after hysterectomy is a rare intraepithelial neoplasia strongly associated with HR-HPV infection. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. In a retrospective study of 170 women hysterectomized due to CIN3 or due to benign uterine pathology, all cases of high-grade VaIN occurred in women with persistent HPV. The most frequent genotype was 16. All these elements suggest that it is a history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered risk factors for the development of high-grade VaIN. A vaginal wall biopsy under colposcopy is recommended to be routinely performed before surgery for patients undergoing hysterectomy due to CIN3 or stage IA cervical cancer, which will help determine the necessary extent of vaginal resection during the procedure.

The data from the literature show that women undergoing a LEEP due to CIN3 have a greater risk of having subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue, and they show mixed results. This study aimed to investigate the incidence of high-grade or severe VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease and illustrate the treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent a laparoscopic hysterectomy due to high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and a diagnosis of high-grade VaIN was 18 months. Results: High-grade or severe VaIN was found in eight patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized due to CIN3 showed an eight-fold greater risk than women hysterectomized due to benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized due to benign disease. The risk of developing VaIN is greater in women with viral persistence. Conclusion: All these elements suggest that it is a history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered risk factors for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing.