Co-infections of HPV16/18 with other high-risk HPV types and the risk of cervical carcinogenesis: A large population-based study

Abstract

Objective: Human papillomavirus (HPV) 16/18 genotyping is an effective method for triage of high-risk (hr) HPV-positive women in primary hrHPV screening for cervical cancer. The present study aimed to evaluate whether co-infected with other hrHPV types will affect the risk of cervical carcinogenesis in HPV16/18 positive women.

Methods: A total of 313,704 women aged ≥30 years were screened in China. Among them, 4,933 HPV16/18-positive participants underwent colposcopy-directed biopsy. The HPV genotypes were identified using the Cobas HPV genotyping system. Multinomial logistic regression was used to model different HPV16/18 infection patterns.

Results: The overall prevalence rates of hrHPV and HPV16/18 were 7.85% (24,456/311,382) and 1.95% (6,086/311,382) respectively. Among HPV16/18 positive individuals, 33.24% (2,023/6,086) were co-infection with multiple types. Of the 4933 women who underwent colposcopy, their HPV16/18 infection patterns were as follows: 52.38% (2,584/4,933) HVP16 only, 23.54% (1,161/4,933) HPV16 + other hrHPVs, 14.98% (739/4,933) HPV18 only, 6.83% (337/4,933) HPV18 + other hrHPVs, 1.13% (56/4,933) HPV16 + 18, 1.13% (56/4,933) HPV16 + 18+other hrHPVs. After adjusting for cofactors, compared with single HPV16 infection, the risk of developing cervical intraepithelial neoplasia (CIN) grade 3 or greater (CIN3+) was significantly lower in HPV16 + other hrHPVs group (odds ratio [OR] = 0.637, 95% confidence interval [CI] = 0.493-0.822).

Conclusion: HPV16/18 co-infection with other hrHPVs is a common phenomenon. Different HPV16/18 infection patterns may influence the risk of cervical carcinogenesis. HPV16 co-infected with other hrHPVs appears to have a lower associated risk of CIN3+ in ≥30 years old women.

Keywords: CIN3; Cervical cancer; HPV co-infections; HPV16; Primary HPV testing.