Ningshao Xia

Variations in the Natural History of High-Risk HPV Types Following HPV-16/18 Bivalent Vaccination in Females Aged 18-45 Years

Existing evidence regarding the impact of vaccination on the natural history of high-risk human papillomavirus (HPV) infections remains limited, understanding such effects is essential for optimizing cervical cancer screening in post-vaccination era. Using 10-year follow-up data from a phase 3 randomized trial of the Escherichia coli-produced HPV-16/18 bivalent vaccine (NCT01735006) and its extension study (NCT05045755, NCT04969445), we compared the spectra and natural history (persistence, clearance, and progression) of high-risk HPV infections between vaccinated and unvaccinated females aged 18-45 years. Data was analyzed using the Cox regression and the competing risk model. Our findings indicate that vaccination reduces the burden of HPV-16/18-associated lesions (HR = 0.12, p = 0.0041) primarily by preventing incident infections (HR = 0.45, p < 0.0001) and modifying the natural history of breakthrough infections (enhancing clearance: 98.5% vs. 93.8%, p < 0.0001; and attenuating progression: 1.5% vs. 6.2%, p = 0.0420). Conversely, the elevated burden of HPV-52-associated lesions (HR = 3.06, p = 0.0303) observed in the vaccine group stems mainly from altered natural history (reduced clearance: 90.3% vs. 97.9%, p = 0.0144; and increased progression: 9.7% vs. 2.1%, p = 0.0421), rather than an increase in incidence (HR = 1.09, p = 0.2669). In this work, the observed shifts in HPV infection profiles and natural history between vaccinated and unvaccinated populations suggest that cervical cancer screening recommendations may warrant adjustment for vaccinated individuals.

Comparing immunogenicity of the Escherichia coli-produced bivalent human papillomavirus vaccine in females of different ages

The safety and efficacy of a recently licensed Escherichia coli (E. coli)-produced bivalent HPV vaccine have been shown. Specific antibody levels are important indicators to evaluate the efficacy of vaccination. Therefore, we compared the immunogenicity of this HPV 16/18 vaccine in females of different ages in this study. Immunogenicity of the vaccine was analyzed in the per-protocol sets for immunogenicity (PPS-I) of a phase III trial and an immune-bridging trial. The serum samples were collected at month 0 and one month after the final dose (month 7) to assess the specific IgG antibody levels by ELISA. The seroconversion rates, geometric mean concentration (GMC), and geometric mean increase (GMI) were used to assess the immunogenicity of the test vaccine. The non-linear association of antibody levels with age was estimated via natural cubic splines and the Akaike information criterion was used to assess optimal model. By combining the PPS-I data from the two trials, nearly all of the females seroconverted for both HPV types. In the 3-dose group, the GMC of IgG to both HPV types decreased with increasing age, especially in adolescent girls and young women. For HPV-16 and -18, the declining trend slowed down in women older than 32 and 35 years old, respectively. The GMI ranged from 648 to 80 for HPV-16 and from 218 to 42 for HPV-18. In the 2-dose group, the specific antibodies for HPV-16 and -18 peaked in girls aged 10 years with GMIs of 401 and 98, respectively, and then decreased with age. The E. coli-produced bivalent HPV-16/18 vaccine induced specific antibody responses in females aged 9-45 years. The antibody levels were inversely associated with age, and the declining trends slowed down in women older than 32 or 35 years for HPV-16 and -18, respectively.