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Papillomavirus Res. 2019 Jul 15;8:100177. doi: 10.1016/j.pvr.2019.100177. [Epub ahead of print]

Is one dose of human papillomavirus vaccine as effective as three?: A national cohort analysis.

Author information

1
National HPV Vaccination Program Register, VCS Population Health, VCS Foundation, East Melbourne, Victoria, Australia; Melbourne School of Population and Global Health, University of Melbourne, Victoria, Australia. Electronic address: jbrother@vcs.org.au.
2
Screening Analysis and Monitoring Unit, Australian Institute of Health and Welfare, Canberra, Australia. Electronic address: Alison.budd@aihw.gov.au.
3
Screening Analysis and Monitoring Unit, Australian Institute of Health and Welfare, Canberra, Australia. Electronic address: christopher.rompotis@aihw.gov.au.
4
Screening Analysis and Monitoring Unit, Australian Institute of Health and Welfare, Canberra, Australia. Electronic address: Natasha.Bartlett@aihw.gov.au.
5
National HPV Vaccination Program Register, VCS Population Health, VCS Foundation, East Melbourne, Victoria, Australia; Melbourne School of Population and Global Health, University of Melbourne, Victoria, Australia. Electronic address: mmalloy@vcs.org.au.
6
Screening and Preventive Health Services, Department of Health and Human Services, Melbourne, Victoria, Australia. Electronic address: Rachael.Andersen@dhhs.vic.gov.au.
7
Cancer Screening Services, Department of Health, Northern Territory Government, Casuarina, Northern Territory, Australia. Electronic address: Kim.Coulter@nt.gov.au.
8
ACT Cervical Screening Program, Population, Health Protection and Prevention, ACT Health, Canberra, Australian Capital Territory, Australia. Electronic address: Peter.Couvee@act.gov.au.
9
WA Cervical Cancer Prevention Program, Women and Newborn Health Service, North Metropolitan Health Service, Western Australia, Australia; Institute for Health, University of Notre Dame Australia, Fremantle, Western Australia, Australia. Electronic address: Nerida.Steel@health.wa.gov.au.
10
Population Screening and Cancer Prevention, Tasmanian Health Service, Hobart, Tasmania, Australia. Electronic address: gail.ward@ths.tas.gov.au.
11
VCS Foundation, Carlton, Victoria, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia. Electronic address: msaville@vcs.org.au.

Abstract

AIM:

Prophylactic human papillomavirus (HPV) vaccines are highly effective at preventing pre-cancerous cervical lesions when given in a three-dose schedule. Some post-hoc trial data suggest that one dose prevents HPV infection. If one dose could prevent pre-cancerous cervical lesions, then global cervical cancer prevention would be greatly facilitated. We assessed the effectiveness of quadrivalent HPV vaccine by number of doses against cervical intraepithelial neoplasia (CIN) 2 or 3/adenocarcinoma-in-situ (AIS)/cancer in Australia up to seven years post vaccination.

METHODS:

We linked registry data from all 8 jurisdictional cervical screening registers, with the national HPV vaccination register, death index and cancer registers for all Australian women aged 15 or under when eligible for vaccine who screened between April 2007 (when vaccination commenced) and 31 December 2014. We performed Cox proportional hazard regression, adjusted a priori for age, socioeconomic status, and area of residence, to estimate hazard ratios of histologically confirmed CIN2/CIN3/AIS/cancer.

RESULTS:

We included 250,648 women: 48,845 (19·5%) unvaccinated, 174,995 (69·8%) had received three doses, 18,190 (7·3%) two doses and 8,618 (3·4%) one dose. The adjusted hazard ratio was significantly lower for all dose groups compared to unvaccinated women (1 dose 0·65 (95%CI 0·52-0·81), 2 doses 0·61 (0·52-0·72) and 3 doses 0·59 (0·54-0·65).) With adjustment for age at vaccination amongst the vaccinated group, the adjusted hazard ratios for one dose and two dose recipients were comparable to three dose recipients (one dose 1.01 (95%CI 0.81-1.26), two doses 1.00 (0.85-1.17).) Multiple sensitivity analyses, including use of different dose assignment methods, produced consistent findings. Comparison with a historical cohort of age matched women showed that the result was not due to herd protection alone.

CONCLUSIONS:

One dose had comparable effectiveness as two or three doses in preventing high-grade disease in a high coverage setting. These findings support the hypothesis that one dose vaccination may be a viable strategy when working towards the global elimination of cervical cancer.

KEYWORDS:

Australia; Cervical intraepithelial neoplasia; Effectiveness; Human papillomavirus; Vaccination

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