HPV Vaccination in China: Evaluating Efficacy and Safety of Bivalent, Quadrivalent, and Nonavalent Vaccines

Introduction

Cervical cancer is the fourth most common cancer among women worldwide. In 2022, it resulted in about 660,000 new cases and 350,000 deaths, primarily affecting low- and middle-income countries. Persistent infection with human papillomavirus (HPV) is the leading factor in the development of cervical cancer. HPV types 16 and 18 account for 71% of cervical cancer cases and are also linked to various other cancers in the anogenital tract and head and neck.

There are twelve high-risk HPV types that increase cancer risk, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. The prevalence of these HPV types varies by region. For example, in Taiwan, Japan, and East Africa, HPV type 52 is most common, while type 16 is predominant in many other areas. In Europe, HPV16, 31, and 18 prevail. Notably, studies in China show that HPV16, 52, and 58 are the most common high-risk types among women.

Preventing cervical cancer focuses on HPV vaccination and early detection and treatment of precancerous lesions. In November 2020, the World Health Organization (WHO) introduced a strategy aimed at eliminating cervical cancer as a public health issue. This strategy emphasizes HPV vaccination as an effective preventive measure.

Since the first HPV vaccine was introduced in 2006, three main vaccine types are available: bivalent, quadrivalent, and nonavalent. In China, two domestic bivalent vaccines (Cecolin® and Walrinvax®) are licensed, along with three imported vaccines (Cervarix®, Gardasil®, and Gardasil 9®). These options provide varied protection against HPV.

Cecolin 2, an E. coli-produced bivalent vaccine, is cost-effective and well-tolerated. It has shown high efficacy against HPV16- and 18-related high-grade lesions in clinical trials. Long-term studies confirm the efficacy of the bivalent (Cervarix 2) and quadrivalent (Gardasil 4) vaccines against HPV16/18-related cervical intraepithelial neoplasia (CIN). The nonavalent Gardasil 9 vaccine maintains strong antibody responses for approximately 10 years.

In August 2020, China launched its first free government-led HPV vaccination campaign. Inner Mongolia’s Ordos City and Guangdong Province initiated free vaccinations for eligible girls. However, delayed domestic trial data slowed the entry of HPV vaccines into the market.

Research is needed to assess the effectiveness and side effects of different HPV vaccines used in China. Current studies on the immunogenicity of Cecolin, especially concerning HPV-neutralizing antibodies, are limited. While Cecolin has shown comparable immunogenicity to Gardasil, there is a lack of comprehensive immune response analysis.

To address this gap, our study includes fully immunized females in Guangzhou City who received bivalent, quadrivalent, and nonavalent HPV vaccines. We utilized the pseudovirion-based neutralization assay (PBNA) to measure neutralizing antibodies, following WHO’s recommended standards.