Ten-year evaluation of HPV vaccine influence on non-vaccine-type-related cervical infections and precancers in Chinese females - follow-up from a randomized control trial

Sep 29, 2026

Uploaded by Fahsai

Long-term effects of human papillomavirus (HPV) vaccination on untargeted HPV types remain poorly understood. This study evaluated how AS04-HPV-16/18 vaccination influenced non-vaccine-type infections and precancers using post-hoc analyses of China’s first HPV vaccine randomized trial, incorporating a 10-year extended follow-up. Virological and pathological endpoints were used to assess cross-protection, type replacement, and grade 2-or-worse cervical intraepithelial neoplasia outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Introduction

Global burden of cervical cancer

HPV vaccines and limitations

Cross-protection vs type replacement

Methods

Randomized trial design and follow-up

Post-hoc analyses and endpoints

Results

Cross-protection against non-vaccine types

Precancer outcomes (CIN2+)

Type replacement assessment

Conclusions

Journal of the National Cancer Center 5 (2025) 586–592 Contents lists available at ScienceDirect Journal of the National Cancer Center journal [homepage:](homepage: www.elsevier.com/locate/jncc)[ www.elsevier.com/locate/jncc](homepage: www.elsevier.com/locate/jncc) | Full Length Article | | | | | | --- | --- | --- | --- | --- | | Ten-year evaluation of HPV vaccine inﬂuence on non-vaccine-type-related cervical infections and precancers in Chinese females: follow-up from a randomized control trial | | | | | | Tianmeng Wen1,†, Changchang Dun2,†, Shangying Hu1, Qinjing Pan1, Xun Zhang1, Fanghui Zhao 1,2,∗
1 Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2 School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China | | | | | | a r t i c l e | i n f o | | a b s t r a c t | | | Keywords: | | | Objective: The long-term inﬂuence of human papillomavirus (HPV) vaccination on untargeted types is poorly understood. The study assessed the inﬂuence of AS04-HPV-16/18 vaccination on non-vaccine-type infections and precancers through post-hoc analyses of a 10-year follow-up of China’s ﬁrst HPV vaccine trial.
Methods: In the clinical trial, females aged 18–25 years (N = 6051) were randomized 1:1 to receive either three doses ofAS04-HPV-16/18 vaccine or control and followed for 6 years. After this trial, all participants were invited to an extended 10-year follow-up. The present post-hoc analyses evaluated cross-protection and type replacement based on virological and pathological endpoints.
Results: The AS04-HPV-16/18 vaccine provided 43.15 %(95 % CI: 20.17 %–59.96 %) cross-protection against 6-month persistent infections related to HPV-31/33/45, while cross-protection against other non-vaccine types (HPV-35/39/51/52/56/58/59/66/68) was non-signiﬁcant. Notably, an increase in non-vaccine-preventabletype-related cervical intraepithelial neoplasia of grade 2 (CIN2) or worse was noted in the vaccine group (attributable proportion: 48.40 %), compared to 29.52 % in the control group (P = 0.020). No signiﬁcant diﬀerencesin incidence or prevalence of non-vaccine-preventable-type infections were found between groups.
Conclusions: A signiﬁcant increase in precancers caused by the non-vaccine-preventable types was demonstrated, despite no evidence of viral replacement 10 years post-vaccination. | | | Human papillomavirus Genotype attribution Type replacement Cross-protection | vaccines | | | | | Cervical intraepithelial | neoplasia | | | | 1. Introduction Cervical cancer is a global health issue, particularly aﬀecting females in low-and middle-income countries (LMICs). In 2022, China accounted for 22.8 % of the new cases and 16.0 % of deaths worldwide.1 Approximately 70 % of cervical cancer cases are attributable to human papillomavirus (HPV) types 16 and 18, while an additional 20 % are linked to types 31, 33, 45, 52, and 58.2 With prophylactic HPV vaccines recognized by the WHO as foundational for accelerating cervical cancer elimination,3 over 140 countries have incorporated them into national immunization programs (NIPs).4 However, due to the high cost of 9-valent HPV vaccines, nearly 70 %(95 out of 142) of these countries rely on bivalent or/and quadrivalent vaccines,5 which do not protect against some high-prevalence types such as 31, 52, and 58.6 In addition, existing HPV vaccines target highly con- ∗ Corresponding author. E-mail address: [zhaofangh@cicams.ac.cn](zhaofangh@cicams.ac.cn) (F. Zhao).† These authors contributed equally to this work. served, type-speciﬁc L1 proteins as antigens, limiting cross-protection against multiple HPV types.7 Although previous studies have shown some level of cross-protection against infection of several non-vaccine types,8 , 9 data rema

FAQs

What was the main objective of the 10-year evaluation study?

To assess the long-term influence of AS04-HPV-16/18 vaccination on infections and precancers caused by HPV non-vaccine types in Chinese females.

How were participants followed in this trial and post-hoc analysis?

Females aged 18–25 years were randomized 1:1 to receive three doses of AS04-HPV-16/18 vaccine or control and were followed for 6 years, after which all participants were invited to an extended 10-year follow-up.

Did vaccination show evidence of viral type replacement after 10 years?

No evidence of viral replacement was demonstrated 10 years post-vaccination, although precancers related to non-vaccine-preventable types increased in the vaccine group.

Sep 29, 2026

Uploaded by Fahsai