Clinical characteristics and diagnostic performance of vaginal squamous cell carcinoma after hysterectomy

Vaginal squamous cell carcinoma (SCC) is a rare gynecological malignancy. Current guidelines do not recommend routine cancer screening after hysterectomy for non-cervical conditions based on the assumption of negligible risk. However, clinical characteristics of vaginal SCC in post-hysterectomy women remain inadequately defined, particularly for those with non-cervical indications. We conducted a retrospective cohort study of 227 patients with vaginal SCC diagnosed at a Chinese tertiary center between 2017 and 2025. Clinical characteristics, high-risk human papillomavirus (HPV) status, diagnostic yields of cytology, colposcopy, ultrasound and MRI, and latency from hysterectomy to cancer diagnosis were analyzed. We found that 66.5% (151/227) of vaginal SCC cases occurred in women with prior hysterectomy; 86.1% had surgery for cervical lesions and 13.9% for non-cervical indications. The overall high-risk HPV positivity rate was 94.7%, with HPV16 predominating (74.9%). Regular post-hysterectomy surveillance was associated with earlier stage at diagnosis: 90.6% of surveilled patients presented with stage I disease versus 65.8% of non-surveilled patients. Latency to diagnosis was significantly shorter for women with prior cervical lesions (median 46.5 versus 120 months). Cytology and colposcopy demonstrated diagnostic yields exceeding 90%, while imaging showed lower detection rates. Vaginal SCC after hysterectomy is predominantly HPV-driven, including in women with non-cervical indications. Regular post-hysterectomy surveillance is strongly associated with earlier stage at diagnosis. While universal screening is not warranted due to disease rarity, these findings support individualized HPV-informed risk counseling for sexually active women after hysterectomy and reinforce current surveillance recommendations for those with prior cervical lesions. Vaginal squamous cancer is rare, and little is known about its development in women after hysterectomy. Current guidelines assume low risk after hysterectomy for non-cervical reasons, so routine follow-up is not recommended. We studied 227 women diagnosed with vaginal squamous cancer at a Chinese hospital between 2017 and 2025. Most had prior hysterectomy, mainly for precancerous cervical conditions. However, one in ten had hysterectomy for non-cervical reasons like fibroids. Nearly all tumors were linked to HPV. Women with regular check-ups after hysterectomy were diagnosed at much earlier stages than those without follow-up. These findings suggest current risk assumptions may need updating. Personalized discussions about HPV risk could benefit sexually active women after hysterectomy. Xiao, Xiao, Su et al., conduct a retrospective cohort study of 227 patients with vaginal squamous cell carcinoma to characterize post-hysterectomy cases, HPV status, diagnostic performance and timing of diagnosis. Vaginal SCC is predominantly HPV-driven, frequently occurs after hysterectomy, and regular surveillance is associated with earlier-stage detection, while cytology and colposcopy show the highest diagnostic yields.