Effectiveness of prophylactic HPV vaccines against cervical abnormalities and HPV infection in Japan: The J-HERS 2021 multicenter study

Abstract

This study investigated the efficacy of the prophylactic human papillomavirus (HPV) vaccine, which was initiated between 2009 and 2013 in Japan. The study involved 1529 eligible women aged 16-39 years who visited 11 outpatient clinics in Japan for various reasons. These patients underwent HPV genotype analysis and a Pap test of cervical cell samples. A total of 299 women (19.6%) had received the prophylactic HPV vaccine (bivalent:quadrivalent vaccine ratio = 2:1). Of the 5062 participants in the Japanese Human Papillomavirus Disease Education and Research Survey (J-HERS 2011), which was conducted in the pre-vaccination era, 3236 eligible participants were included as controls. In this study (J-HERS 2021), the highest rate of HPV vaccination (53%) was observed in patients aged 22-27 years. Vaccinated individuals exhibited a 49% rate of protection against low-grade intraepithelial lesions (LSILs) and atypical squamous cells, not excluding high-grade squamous intraepithelial lesions (ASCH) or worse (LSIL/ASCH+), and a 100% rate of protection against high-grade squamous intraepithelial lesions (HSILs) or worse (HSIL+). Significant reductions in HPV16 (95%) and HPV18 (100%) infections were noted, but no differences were observed in HPV6 and HPV11 infections. The prevalences of HPV51 and HPV59 increased with vaccination, although these changes were not confirmed in the comparative study with J-HERS 2011. Comparing the prevaccination (J-HERS 2011) and postvaccination (J-HERS 2021) periods, 43%, 51%, 88%, and 62% reductions in HPV16, HPV18, HPV16/18, and HPV31/58 infection rates were observed, respectively. Similarly, 62% and 71% reductions in LSIL/ASCH+ and HSIL+ rates were noted, respectively. There were 88% and 87% reductions in LSIL/ASCH+ and HSIL+ rates in 16-21- and 28-33-year-old patients, respectively. Bivalent or quadrivalent vaccines provided 100% protection against high-grade squamous cell lesions (suggestive of CIN2 or CIN3) in young women aged <39 years at 9-12 years after initiation of Japan's first nationwide HPV vaccination program. Cross-protection against HPV31 and HPV58 is likely to occur, although some HPV-type replacements are inconsistent across vaccination regimens. This demonstrates the effectiveness of the HPV vaccine. However, continuous monitoring of cervical cancer and precancer is necessary in younger generations (born 1997-2007), who were rarely vaccinated due to the prolonged suspension of the vaccine recommendations in Japan.

Keywords: HPV type; bi-valent of quadri-valent prophylactic HPV vaccine; cervical abnormality; efficacy; human papillomavirus.