Gender‐neutral vaccination provides improved control of human papillomavirus types 18/31/33/35 through herd immunity: Results of a community randomized trial (III)

• Published in: International journal of cancer 2018-11, Vol.143 (9), p.2299-2310
• Main Authors: Lehtinen, Matti, Luostarinen, Tapio, Vänskä, Simopekka, Söderlund‐Strand, Anna, 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, Nieminen, Pekka, Dillner, Joakim, Dubin, Gary, Garnett, Geoff
• Format: Article
• Language: English
• Subjects: Adolescent; Cancer; Child; Cohort Studies; Female; Females; Finland - epidemiology; Follow-Up Studies; Gender; gender‐neutral; Health risks; Hepatitis; Hepatitis B; herd effect; Herd immunity; Human papillomavirus; Humans; Immunity, Herd - immunology; impact; Male; Males; Medical research; Medicin och hälsovetenskap; Papillomaviridae - classification; Papillomaviridae - immunology; Papillomavirus Infections - epidemiology; Papillomavirus Infections - immunology; Papillomavirus Infections - prevention & control; Papillomavirus Vaccines - therapeutic use; Prognosis; randomized trial; Sex Factors; Typing; vaccination; Vaccine efficacy; Vaccines; Viruses
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.31618

With optimal strategy, human papillomavirus (HPV) vaccines have the potential to control HPV. We have assessed vaccine efficacy (VE), herd effect (HE) of HPV vaccination and overall protective effectiveness (PE) against high‐risk HPV infections by HPV type and vaccination strategy in a community‐randomized trial using the bivalent HPV16/18 vaccine. We randomized 33 communities to gender‐neutral HPV vaccination (Arm A), HPV vaccination of girls and hepatitis B‐virus (HBV) vaccination of boys (Arm B) and gender‐neutral HBV vaccination (Arm C). Entire 1992–1995 male (40,852) and female (39,420) birth cohorts were invited, and 11,662 males and 20,513 females vaccinated with 20–30% and 45% coverage in 2007–2010. During 2010–2014, 11,396 cervicovaginal samples were collected from 13,545 18.5‐year‐old attendees. HPV typing was performed by a high‐throughput PCR. VE was calculated for HPV vaccinated women and HE for non‐HPV‐vaccinated women, using the HBV vaccinated, for HE all non‐HPV vaccinated, Arm C women as controls. PE was calculated as coverage rate‐weighted mean of VE + HE. HPV16/18/45 and 31/33/35 VEs varied between 86–94% and 30–66%, respectively. Only the gender‐neutral vaccination provided significant HEs against HPV18 (61%) and HPV31 (72%) in the 1995 birth cohort—increased HEs against HPV33 (39%) and HPV35 (42%) were also observed. Due to the increased HEs, PEs for HPV16/18/45 and HPV31/33/35 were comparable in the gender‐neutral arm 1995 birth cohort. High vaccine efficacy against HPV16/18/45 and, gender‐neutral vaccination‐enforced, herd effect against HPV18/31/33/35 by the bivalent vaccine rapidly provides comparable overall protective effectiveness against six oncogenic HPV types: 16/18/31/33/35/45. What's new? Human papillomavirus (HPV) vaccination coverage has remained low to moderate in most countries. An optimal vaccination program should therefore aim to generate herd effect even with low coverage. Here, the authors report results from a community‐randomized trial with low to moderate vaccination coverage comparing the bivalent vaccine efficacy, herd effect, and overall protective effectiveness of gender‐neutral or girls‐only vaccination strategies against up to 16 HPV types with special emphasis on types 16/18/31/33/35/45. High vaccine efficacy against HPV16/18/45 and gender‐neutral vaccination‐enforced herd effect against HPV18/31/33/35 by the bivalent vaccine rapidly provided comparable overall protective effectiveness against six high‐ri