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. 2025 Apr 4:16:1546166.
doi: 10.3389/fmicb.2025.1546166. eCollection 2025.

Epidemiologic evaluation of human papillomavirus type competition in unvaccinated women from Xiamen, China

Yu Chen #  1   2 , Qing Li #  3 , Liya Du #  4 , Zhuowen Du  2 , Yixi Zhou  1 , Yanru Huang  1 , Jian Zhang  1 , Wenbo Wang  1 , Lutan Zhang  1 , Jieqiong Xie  1 , Chao Xu  5 , Yunsheng Ge  1 , Xingmei Yao  1 , Yulin Zhou  1   2
Affiliations

Epidemiologic evaluation of human papillomavirus type competition in unvaccinated women from Xiamen, China

Yu Chen et al. Front Microbiol. .

Abstract

Background: Human papillomavirus (HPV) vaccination is expected to reduce the burden of cervical cancer and other HPV-related diseases. However, if competition exists among HPV types, type replacement may occur following the reduction of vaccine-targeted types. Here, we conducted the study to explore natural HPV type competition in unvaccinated women.

Methods: HPV DNA test results from cervical samples collected between January 2013 and July 2023 at Xiamen University's Women and Children's Hospital were analyzed. In cross-sectional study, first-visit HPV genotyping results were used, and logistic regression model was constructed to evaluate interactions between vaccine-targeted and other HPV types. In cohort of women with multiple visits, the risk of acquiring other HPV types was compared between women infected with vaccine-targeted types and those HPV-negative using Cox proportional hazards model.

Results: Among 159,049 women, 19.8% tested HPV-positive, with 5.1% having multiple types. Significant negative associations were observed between HPV-6 and HPV-72 (OR: < 0.01; 95%CI: < 0.01-0.03), HPV-18 and HPV-72 (OR: < 0.01; 95%CI: < 0.01-0.02), HPV-31 and HPV-83 (OR: < 0.01; 95%CI: < 0.01-0.55), HPV-33 and HPV-26 (OR: < 0.01; 95%CI: < 0.01-0.81), HPV-45 and HPV-55 (OR: < 0.01; 95%CI: < 0.01- < 0.01), HPV-56 and HPV-26 (OR: < 0.01; 95%CI: < 0.01-0.09), as well as HPV-59 and HPV-69 (OR: < 0.01; 95%CI: < 0.01-0.68), suggesting potential type competition. However, no type competition pair was found in the cohort study. Conversely, women with vaccine-targeted types had a higher risk of acquiring other types (HR > 1.0).

Conclusions: Our findings suggested that HPV-6 and HPV-72, HPV-18 and HPV-72, HPV-31 and HPV-83, HPV-33 and HPV-26, HPV-45 and HPV-55, HPV-56 and HPV-26, HPV-59 and HPV-69 were potential type competition pairs.

Keywords: HPV vaccine; cervical cancer; human papillomavirus (HPV); infection; type competition.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
A flow diagram summarizing the study steps and data analysis procedures. a. Exposed group: baseline positivity for specific HPV (HPV-6/11/16/18/31/33/45/52/58/35/39/51/56/59/68).
Figure 2
Figure 2
HPV types distribution of single and multiple infections. The colors purple and pink indicate single and multiple infections.
Figure 3
Figure 3
Age-adjusted odds ratios (ORs) for coinfections involving vaccine-targeted HPV types and other HPV types. (a) HPV-6 and other HPV types, (b) HPV-11 and other HPV types, (c) HPV-16 and other HPV types, (d) HPV-18 and other HPV types, (e) HPV-31 and other HPV types, (f) HPV-33 and other HPV types, (g) HPV-45 and other HPV types, (h) HPV-52 and other HPV types, and (i) HPV-58 and other HPV types.
Figure 4
Figure 4
Hazard ratios and 95%CI for acquisition of non-vaccine-targeted HPV types in 2 years: women infected with HPV vaccine-targeted types (6, 11, 16, 18, 31, 33, 45, 52, and 58) vs. women with negative for HPV. (a) HPV-6 and other HPV types, (b) HPV-11 and other HPV types, (c) HPV-16 and other HPV types, (d) HPV-18 and other HPV types, (e) HPV-31 and other HPV types, (f) HPV-33 and other HPV types, (g) HPV-45 and other HPV types, (h) HPV-52 and other HPV types, and (i) HPV-58 and other HPV types.
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