Women who have taken the bivalent human papillomavirus virus vaccine may still be vulnerable to HPV types not covered by the vaccine, according to findings from the  Costa Rica HPV Vaccine Trial published in The Lancet Oncology.¹

Participants, aged 18 to 25 years and who were generally healthy, were included in this study. A total of 3727 women were administered HPV vaccine, while the control group consisted of 2836 women who received hepatitis A vaccine. The HPV vaccine used in this study was the bivalent AS04-adjuvanted vaccine targeting HPV subtypes 16 and 18. After 4 years, women in the control group were also administered the HPV vaccine and they left the study. In their place, 2836 unvaccinated women entered the trial as the control group. The HPV vaccine group and the unvaccinated controls were followed further for a period of 7 years.

There was an excess of 9.2 CIN2+ (cervical intraepithelial neoplasia grade 2 or higher) due to HPV types not covered by the vaccine per 1000 women who had received the HPV vaccine compared to the unvaccinated controls resulting in  negative vaccine efficacy of -71.2% for these HPV types. With regard to CIN3+ lesions from the HPV types not covered by the vaccine, 8.3 more lesions were detected in the HPV vaccine group compared to the unvaccinated participants, with negative vaccine efficacy of -135%.

However, the vaccination was overall beneficial with 27 fewer CIN2+ lesions across all genotypes per 1000 women who received the vaccine during follow-up of 11 years. Also, there were fewer CIN3+ lesions (8.7) across all the HPV genotypes per 1000 vaccinated women.

HPV vaccination is routinely done at 11-12 years of age. As per the CDC, women who were inadequately vaccinated at younger age can still take the vaccine up to 26 years of age, but not beyond this. HPV 16 and 18 cause almost 70% of cervical cancers.

The higher rates of CIN2/3+ events in this study raise a possibility that the HPV types not covered by the vaccine could offset the protective effects of HPV vaccination. One must therefore continue to be cautious even if vaccinated. But since the vaccine was overall beneficial, HPV vaccination remains an important means for primary prevention of cervical cancer.

Reference

1. Jaimie Z Shing, et al; Costa Rica HPV Vaccine Trial Group. Precancerous cervical lesions caused by non-vaccine-preventable HPV types after vaccination with the bivalent AS04-adjuvanted HPV vaccine: an analysis of the long-term follow-up study from the randomised Costa Rica HPV Vaccine Trial. Lancet Oncol. 2022 Jun 13;S1470-2045(22)00291-1. doi: 10.1016/S1470-2045(22)00291-1.