Research progress on HPV-related vaginal wall lesions after hysterectomy

Hysterectomy is one of the most commonly performed gynecological surgeries worldwide. Vaginal wall lesions after hysterectomy, particularly vaginal intraepithelial neoplasia (VaIN) associated with High-risk human papillomavirus (HR-HPV) infection, have become a focal point in gynecological oncology research. With the widespread implementation of cervical cancer screening programs and the increasing awareness of HPV-related diseases, the detection rate of VaIN has gradually increased. This review systematically analyzes the research progress in various aspects of HPV-related vaginal wall lesions after hysterectomy, including epidemiological characteristics, risk factors, pathogenesis, clinical features, diagnostic strategies, treatment modalities, and follow-up management. Epidemiological studies have shown that although VaIN accounts for less than 1% of all lower genital tract precancerous lesions, its incidence is significantly higher in patients who have undergone hysterectomy for cervical intraepithelial neoplasia (CIN) or cervical cancer. The main risk factors include age, menopausal status, preoperative high-grade CIN, high-risk HPV infection (especially HPV16 and HPV18), immunosuppressive status, surgical approach, positive surgical margins, smoking, multiple sexual partners, and vaginal microecological disorders. The pathogenesis of VaIN after hysterectomy is complex and multifactorial. Persistent HPV infection plays a central role. The E6 and E7 oncoproteins of high-risk HPV promote malignant transformation by degrading p53 and inactivating retinoblastoma protein (pRb), leading to uncontrolled cell proliferation. Surgery-induced anatomical changes, local immune microenvironment alterations, and latent HPV reactivation collectively contribute to VaIN development. Diagnosis requires a standardized approach combining HPV testing, liquid-based cytology (TCT), colposcopy, and targeted biopsy. Colposcopic examination should focus on the vaginal apex, suture line, and lateral fornices where lesions commonly hide. Treatment should be individualized based on lesion grade, extent, location, patient age, fertility requirements, and previous treatments. Options include surgical excision (partial vaginectomy, vaginal apex resection), ablative therapy (CO₂ laser), topical medications (imiquimod), photodynamic therapy (PDT), and radiotherapy for invasive cancer. Despite effective initial treatment, VaIN has a high recurrence rate, with cumulative recurrence reaching up to 80% within 2-5 years. Long-term follow-up with risk-stratified surveillance is essential. Annual HPV testing combined with TCT is recommended for high-risk patients. Artificial intelligence-assisted colposcopy and molecular biomarkers represent promising future directions. This review provides a theoretical basis for standardized diagnosis and treatment of VaIN after hysterectomy and identifies current challenges and controversies in clinical practice.