Effectiveness on high-grade cervical abnormalities and long-term safety of the quadrivalent human papillomavirus vaccine in Japanese women

• Published in: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Vol. 25; no. 7; pp. 520 - 525
• Main Authors: Sakamoto, Masaru, Miyagi, Etsuko, Sumi, Yukari, Aisaka, Kohzo, Kuno, Naohiko, Nagano, Hiroshi, Asahara, Saiko, Han, Shi Rong, Wakana, Akira, Murata, Shinya, Sawata, Miyuki, Tanaka, Yoshiyuki
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-07-2019
• Subjects: Adolescent; Adult; Cervical Intraepithelial Neoplasia - epidemiology; Cervical Intraepithelial Neoplasia - prevention & control; Cervical Intraepithelial Neoplasia - virology; Double-Blind Method; Effectiveness; Female; Follow-Up Studies; Human papillomavirus; Humans; Immunization Schedule; Incidence; Japan; Japan - epidemiology; Papillomavirus Infections - epidemiology; Papillomavirus Infections - prevention & control; Papillomavirus Infections - virology; Papillomavirus Vaccines - administration & dosage; Papillomavirus Vaccines - adverse effects; Quadrivalent vaccine; Safety; Time Factors; Uterine Cervical Neoplasms - epidemiology; Uterine Cervical Neoplasms - prevention & control; Uterine Cervical Neoplasms - virology; Vaccination - adverse effects; Vaccination - methods; Young Adult; Japan; Human papillomavirus; Effectiveness; Safety; Japan; Quadrivalent vaccine
• ISSN: 1341-321X; 1437-7780
• DOI: 10.1016/j.jiac.2019.02.012

This study for the first time assessed quadrivalent human papillomavirus (qHPV) vaccine effectiveness against HPV6/11/16/18-related high-grade cervical disease in Japanese women (16–26 years old), as previously demonstrated in overseas trials, and vaccine safety in a longer term (48-month) open-label study (NCT01544478). Participants received three doses of qHPV vaccine (Day 1, Month 2, Month 6). Effectiveness endpoints, assessed in the per-protocol population, included incidence of HPV6/11/16/18-related cervical intraepithelial neoplasia (CIN) Grade 2 or worse (CIN Grade 2 and 3, adenocarcinoma in situ, and/or cervical cancer) as primary endpoint and incidence of external genital lesions (EGLs). Disease related to other high-risk HPV types was also assessed. Adverse events (AEs) and serious AEs (SAEs) were collected from Days 1–15 after any vaccination; vaccine-related SAEs, deaths, and new medical conditions were collected throughout the study. A total of 1030 women received at least one vaccination. No cases of CIN2 or worse or EGLs were reported in the per-protocol population. Injection site-related AEs were reported in 14.5% of participants; most were mild and resolved within 15 days. Vaccine-related systemic AEs occurred in 8.6% of participants, most commonly headache (2.3%), malaise (1.7%), and pyrexia (1.3%). There were no vaccine-related SAEs; one participant discontinued due to a vaccine-related AE of mild uticaria. Overall, qHPV vaccine effectiveness against HPV6/11/16/18-related high-grade cervical disease and EGLs was indicated in Japanese women. The vaccine was well-tolerated, without new safety signals throughout the 48-month study period. Findings are consistent with overseas qHPV vaccine pivotal trials.
clinicaltrials.gov; NCT01544478.