Human papillomavirus vaccine to prevent cervical intraepithelial neoplasia in Japan: A nationwide case‐control study

Abstract

Cervical cancer remains among the most common cancers in women worldwide and can be prevented by vaccination. The Ministry of Health, Labour and Welfare of Japan suspended active recommendation of regular human papillomavirus (HPV) vaccines in 2013 because of various symptoms including chronic pain and motor impairment. This nationwide case‐control study from April 2013 to March 2017 targeted women aged 20‐24 years old at cervical screening. We compared HPV vaccination exposure between those with abnormal and normal cytology. Abnormal cytology was classified based on the results of histological test and we calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 – OR) × 100. A total of 2483 cases and 12 296 controls (one‐to‐five matching) were eligible in 31 municipalities in Japan. The distribution of histological abnormalities among cases was 797 CIN1 (including dysplasia) (32.1%), 165 CIN2 (6.7%), 44 CIN3 (1.8%), and eight squamous cell carcinoma (SCC) (0.3%). The OR of HPV vaccination compared with no vaccination for abnormal cytology, CIN1+, CIN2+, and CIN3+ versus controls was 0.42 (95% CI, 0.34‐0.50), 0.42 (95% CI, 0.31‐0.58), 0.25 (95% CI, 0.12‐0.54), and 0.19 (95% CI, 0.03‐1.15), respectively, equating to a vaccine effectiveness of 58.5%, 57.9%, 74.8%, and 80.9%, respectively. Eight patients had SCC, none was vaccinated. This nationwide case‐control study in Japan demonstrated a substantial risk reduction in abnormal cytology and CIN among women who did versus those who did not receive HPV vaccination.

The difference in the effectiveness of human papillomavirus vaccine based on smoking status

“…Although there were four cases with CIN3+, none was in the inoculation group. Recently, Ikeda et al also reported that the nationwide case–control study in Japan demonstrated a risk reduction of 58% for CIN1+ and 75% for CIN2+ among women with versus those without HPV vaccination 17 . Ozawa et al also reported that the rates of CIN3+ were 0% (0/1002) with vaccination and 0.18% (9/4922) without vaccination in Japan 18 …”

Cervical Cancer Protection in Japan: Where Are We?

“…HPV vaccination led to a significant reduction in the incidence of abnormal cytology in vaccinated women born in 1994-1995 [32]. In a case-control study the size of one-tenth of the total Japanese population, a preventive effect of CIN2 was reported [33]. In research conducted in Matsuyama City, a preventive effect of CIN3 was reported [34].…”

Towards the elimination of cervical cancer in Japan

“…In June 2013, only two months after inclusion in the NIP, the Ministry of Health, Labour, and Welfare announced that, although the vaccine would remain in the NIP and would be free for 12–16-year-old girls, all proactive recommendations for it would be suspended. Over the past eight years, several large-scale epidemiological studies conducted in Japan have shown that the HPV vaccine is effective against both HPV infection [ 6 ] and precancerous disease [ 7 8 ], and safe [ 9 ]. However, as of May 2021, the situation remains unchanged, with the vaccine still available for free to the target age groups but not being proactively recommended.…”