Pattern of multiple human papillomavirus infection and type competition: An analysis in healthy Chinese women aged 18–45 years

ABSTRACT

To assess the pattern of multiple human papillomavirus infection to predict the type replacement postvaccination. A total of 7372 women aged 18–45y from a phase III trial of an Escherichia coli-produced HPV-16/18 vaccine were analyzed at enrollment visit before vaccination. Hierarchical multilevel logistic regression was used to evaluate HPV vaccine type and nonvaccine-type interactions with age as a covariate. Binary logistic regression was construed to compare multiple infections with single infections to explore the impact of multiple-type infections on the risk of cervical disease. Multiple HPV infections were observed in 25.2% of HPV-positive women and multiple infections were higher than expected by chance. Statistically significant negative associations were observed between HPV16 and 52, HPV18 and HPV51/52/58, HPV31 and HPV39/51/52/53/54/58, HPV33 and HPV52/58, HPV58 and HPV52, HPV6 and HPV 39/51/52/53/54/56/58. Multiple HPV infections increased the risk of CIN2+ and HSIL+, with the ORs of 2.27(95%CI: 1.41, 3.64) and 2.26 (95%CI: 1.29, 3.95) for multiple oncogenic HPV infection separately. However, no significant evidence for the type-type interactions on risk of CIN2+ or HSIL+. There is possibility of type replacement between several pairs of vaccine and nonvaccine HPV type. Multiple HPV infection increased the risk of cervical disease, but coinfection HPV types seem to follow independent disease processes. Continued post-vaccination surveillance for HPV 51/52/58 types and HPV 39/51 types separately was essential after the first and second generation of HPV vaccination implementation in China.

KEYWORDS:

• HPV
• multiple infection
• type competition
• type replacement
• postvaccination

Author contribution

Yingying Su, Youlin Qiao, Ting Wu, Jun Zhang, and Ningshao Xia contributed to the study conception and design. Data collection and analysis were performed by Yingying Su, Tingquan Zheng, Zhaofeng Bi, Xinhua Jia, Yufei Li, Xuefeng Kuang, Yuan Yang, Qi Chen, Hongyan Lin, and Yue Huang. Yingying Su and Ting Wu drafted manuscript. All authors critically reviewed the manuscript and approved the final version. The work reported in the paper has been performed by the authors, unless clearly specified in the text.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data will be available beginning 6 months after the major findings from the final analysis of the study have been published, ending 2 y after. Proposals should be directed to [email protected]. To gain access, data requestors will need to sign a data access agreement.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [Grant number: 82072323 to Yingying Su, and 82273640 to Ting Wu], Natural Science Foundation of Fujian Province [Grant number: 2020J01044 to Yingying Su], CAMS Innovation Fund for Medical Sciences of China [Grant number: 2019RU022 to Ningshao Xia], and Fundamental Research Funds for the Central Universities [Grant number: 20720220006 to Ningshao Xia, and 20720200105 to Yingying Su].