Impact of gender‐neutral or girls‐only vaccination against human papillomavirus—Results of a community‐randomized clinical trial (I). Issue 5 (9th November 2017)

• Record Type: Journal Article
• Authors: Lehtinen, Matti; Söderlund‐Strand, Anna; Vänskä, Simopekka; Luostarinen, Tapio; Eriksson, Tiina; Natunen, Kari; Apter, Dan; Baussano, Iacopo; Harjula, Katja; Hokkanen, Mari; Kuortti, Marjo; Palmroth, Johanna; Petäjä, Tiina; Pukkala, Eero; Rekonen, Sirpa; Siitari‐Mattila, Mari; Surcel, Heljä‐Marja; Tuomivaara, Leena; Paavonen, Jorma; Dillner, Joakim; Dubin, Gary; Garnett, Geoffrey
• Is Part Of: International journal of cancer. Volume 142:Issue 5(2018)
• Page Start: 949
• Page End: 958
• Publication Date: 2017-11-09
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31119
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Human papillomavirus (HPV) vaccine is efficacious but the real‐life effectiveness of gender‐neutral and girls‐only vaccination strategies is unknown. We report a community‐randomized trial on the protective effectiveness [(PE) = vaccine efficacy (VE) + herd effect (HE)] of the two strategies among females in virtually HPV vaccination naïve population. We randomized 33 Finnish communities into Arm A) gender‐neutral vaccination with AS04‐adjuvanted HPV16/18 vaccine (11 communities), Arm B) HPV vaccination of girls and hepatitis B‐virus (HBV) vaccination of boys (11 communities) or Arm C) gender‐neutral HBV vaccination (11 communities). All resident 39, 420 females and 40, 852 males born 1992‐95 were invited in 2007–09. Virtually all (99%) 12‐ to 15‐year‐old participating males (11, 662) and females (20, 513) received three doses resulting in uniform 20–30% male and 50% female vaccination coverage by birth cohort. Four years later (2010–14) 11, 396 cervicovaginal samples obtained from 18.5 year‐old women were tested for HPV DNA, and prevalence of cervical HPV infections by trial arm and birth cohort was the main outcome measure. VEs against HPV16/18 varied between 89.2% and 95.2% across birth cohorts in arms A and B. The VEs against non‐vaccine types consistent with cross‐protection were highest in those born 1994–95 for HPV45 (VEA 82.8%; VEB 86.1%) and for HPV31 (VEA 77.6%, VEB 84.6%). The HEs in the non HPV‐vaccinated were statistically significant in those born 1994–95 for HPV18 (HEA 51.0%; 95% CI 8.3–73.8, HEB 47.2%; 6.5–70.2) and for HPV31/33 in arm A (HEA 53.7%; 22.1–72.5). For HPV16 and 45 no significant herd effects were detected. PE estimates against HPV16/18 were similar by both strategies (PEA 58.1%; 45.1–69.4; PEB 55.7%; 42.9–66.6). PE estimates against HPV31/33 were higher by the gender‐neutral vaccination (PEA 60.5%; 43.6–73.4; PEB 44.5%; 24.9–60.6). In conclusion, while gender‐neutral strategy enhanced the effectiveness of HPV vaccination for cross‐protected HPV types with low to moderate coverage, high coverage in males appears to be key to providing a substantial public health benefit also to unvaccinated females. Trial registration www.clinicaltrials.gov.com NCT000534638 Abstract : What's new? Vaccines against cancer‐causing human papillomaviruses (HPVs) effectively prevent HPV infection. However, whether it is better in terms of health and cost to vaccinate only girls or to vaccinate both boys and girls remains unclear. The present report details the results of a community‐randomized trial of the two strategies in an HPV vaccination‐naïve population born between 1992 and 1995 in Finland. Overall, low‐ to moderate‐coverage gender‐neutral vaccination provided the greatest protection against HPV. Gender‐neutral vaccination of early adolescents was associated with significant herd effects and cross‐protection against a number of non‐vaccine HPV types.