Abstract
<title>Abstract</title> <p>Background Persistent human papillomavirus (HPV) infection after menopause is clinically challenging because epithelial atrophy, sampling difficulty, and transformation-zone migration may reduce the reassurance provided by cytology. Although HPV genotyping is now central to risk-based management, lesion burden among cytology-negative postmenopausal women with persistent HPV infection remains insufficiently characterized, particularly when cervical, vaginal, and vulvar disease are assessed together. Methods We conducted a retrospective study of postmenopausal women with persistent human papillomavirus (HPV) infection who were managed in the gynecological outpatient department of Guangdong Provincial Hospital of Chinese Medicine, University Town Branch, from 2023 to 2025. Persistent infection was defined as same-genotype HPV infection lasting at least 12 completed calendar months between the recorded infection-start date and the index visit. Cytology-negative status was defined as negative for intraepithelial lesion or malignancy (NILM) on ThinPrep cytologic testing. The primary pathological outcome was lesion status and grade, classified as no HPV-related lesion, low-grade lesion (LSIL/low-grade lesion), or high-grade lesion (HSIL/high-grade lesion). Secondary outcomes included anatomic lesion site and multicentric lower-genital-tract involvement, defined as HPV-related lesions involving at least two distinct genital sites among the cervix, vagina, and vulva. Results All 353 screened records met the persistent-infection definition. NILM cytology was present in 223 women (63.2%). Among women with NILM cytology, 134 (60.1%) had no HPV-related lesion, 89 (39.9%) had an HPV-related lower genital tract lesion, 79 (35.4%) had a low-grade lesion, 10 (4.5%) had a high-grade lesion, and 22 (9.9%) had multicentric involvement. Compared with women with NILM cytology, women with abnormal cytology had higher odds of low-grade lesion (OR 1.88, 95% CI 1.21–2.92) and high-grade lesion (OR 4.58, 95% CI 2.10–9.97). HPV16/18 positivity was associated with any lesion in the overall cohort (OR 3.02, 95% CI 1.87–4.87) and among NILM women (OR 2.72, 95% CI 1.53–4.84). Multiple HPV infection was associated with multicentric involvement in the overall cohort (OR 2.00, 95% CI 1.05–3.78) and in the NILM subgroup (OR 2.79, 95% CI 1.14–6.82). Conclusions NILM cytology did not exclude clinically meaningful lesion burden in postmenopausal women with persistent HPV infection. HPV16/18 positivity identified women with higher lesion odds, whereas multiple HPV infection was associated with multicentric involvement. These findings support assessment that considers both HPV genotype and the full lower genital tract in postmenopausal persistent HPV management.</p>