Co-detection of human papillomavirus and human herpesvirus in women from Yunnan, China: associations with cervical lesion severity

BACKGROUND: Human papillomavirus (HPV) is necessary but not sufficient for cervical carcinogenesis. Human herpesviruses (HHVs) may act as cofactors, yet evidence is inconsistent. We assessed HPV genotypes, HHVs, and their co-detection patterns across cervical disease grades in Yunnan, China. METHODS: Cervical exfoliated cell samples were collected from women attending gynecology clinics and classified as NILM, CIN1, CIN2, CIN3, or cervical cancer. HPV genotyping and detection of HSV-1/2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8 were performed by PCR based assays. RESULTS: The cohort included 1096 women. Median age increased with disease severity, from 39.00 years in NILM to 51.00 years in cervical cancer (p < 0.001). HPV prevalence was higher in lesion and cancer groups than in NILM (any HPV 48.56% vs. 64.71% to 70.00%, p = 0.033; any high-risk HPV 43.69% vs. 58.82% to 65.12%, p = 0.013). The most frequent genotypes were HPV-52, HPV-16, HPV-58, and HPV-45. HPV-16 positivity increased with severity (p = 0.023), while HPV-18 did not (p = 0.084). Overall HHV DNA detection was 19.89%. CMV was the most frequently detected HHV at 9.67%, followed by HHV-7 at 5.11%, VZV at 3.74%, and EBV at 1.92%. HSV-1/2, HHV-6, and HHV-8 were rarely detected, each in approximately 0.5% of samples. Trend tests revealed no monotonic gradient in any HHV detection rate across lesion grades. VZV detection rates differed significantly across disease categories by Fisher's exact test (p = 0.022). In adjusted models, overall HHV DNA detection was not significantly associated with either CIN2 + or CIN3+. In contrast, high-risk HPV and HPV-16 were consistently associated with increased odds of CIN2 + and CIN3+. Exploratory analyses identified genotype-specific HPV-HHV co-detection patterns, including HPV-26 with HSV-1/2, HPV-83 with EBV, and HPV-45 with CMV. CONCLUSIONS: In this hospital-based cohort from Yunnan, age and high-risk HPV, particularly HPV-16, were associated with cervical disease severity. HHV DNA was detectable in a subset of participants but showed no significant association with CIN2 + or CIN3 + after adjustment. These findings highlight the dominant association of HPV, particularly HPV-16, with cervical lesion severity and provide regional data for future longitudinal studies of HPV-HHV DNA co-detection. CLINICAL TRIAL NUMBER: Not applicable.