Potential effectiveness of prophylactic HPV immunization for men who have sex with men in the Netherlands: A multi-model approach.
Journal
PLoS medicine
ISSN: 1549-1676
Titre abrégé: PLoS Med
Pays: United States
ID NLM: 101231360
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
20
07
2018
accepted:
31
01
2019
entrez:
5
3
2019
pubmed:
5
3
2019
medline:
23
10
2019
Statut:
epublish
Résumé
Men who have sex with men (MSM) are at high risk for anal cancer, primarily related to human papillomavirus genotype 16 (HPV16) infections. At 8.5 per 100,000 per year, the incidence rate of anal cancer among MSM is similar to that of cervical cancer among adult women in the Netherlands. However, MSM are not included in most HPV vaccination programs. We explored the potential effectiveness of prophylactic immunization in reducing anogenital HPV16 transmission among MSM in the Netherlands. We developed a range of mathematical models for penile-anal HPV16 transmission, varying in sexual contact structure and natural history of infection, to provide robust and plausible predictions about the effectiveness of targeted vaccination. Models were informed by an observational cohort study among MSM in Amsterdam, 2010-2013. Parameters on sexual behavior and HPV16 infections were obtained by fitting the models to data from 461 HIV-negative study participants, considered representative of the local MSM population. We assumed 85% efficacy of vaccination against future HPV16 infections as reported for HIV-negative MSM, and age-specific uptake rates similar to those for hepatitis B vaccination among MSM in the Netherlands. Targeted vaccination was contrasted with vaccination of 12-year-old boys at 40% uptake in base-case scenarios, and we also considered the effectiveness of a combined strategy. Offering vaccine to MSM without age restrictions resulted in a model-averaged 27.3% reduction (90% prediction interval [PI] 11.9%-37.5%) in prevalence of anal HPV16 infections, assuming similar uptake among MSM as achieved for hepatitis B vaccination. The predicted reduction improved to 46.1% (90% PI 21.8%-62.4%) if uptake rates among MSM were doubled. The reductions in HPV16 infection prevalence were mostly achieved within 30 years of a targeted immunization campaign, during which they exceeded those induced by vaccinating 40% of preadolescent boys, if started simultaneously. The reduction in anal HPV16 prevalence amounted to 74.8% (90% PI 59.8%-93.0%) under a combined vaccination strategy. HPV16 prevalence reductions mostly exceeded vaccine coverage projections among MSM, illustrating the efficiency of prophylactic immunization even when the HPV vaccine is given after sexual debut. Mode of protection was identified as the key limitation to potential effectiveness of targeted vaccination, as the projected reductions were strongly reduced if we assumed no protection against future infections in recipients with prevalent infection or infection-derived immunity at the time of immunization. Unverified limitations of our study include the sparsity of data to inform the models, the omission of oral sex in transmission to the penile or anal site, and the restriction that our modeling results apply primarily to HIV-negative MSM. Our findings suggest that targeted vaccination may generate considerable reductions in anogenital HPV16 infections among MSM, and has the potential to accelerate anal cancer prevention, especially when combined with sex-neutral vaccination in preadolescence.
Sections du résumé
BACKGROUND
Men who have sex with men (MSM) are at high risk for anal cancer, primarily related to human papillomavirus genotype 16 (HPV16) infections. At 8.5 per 100,000 per year, the incidence rate of anal cancer among MSM is similar to that of cervical cancer among adult women in the Netherlands. However, MSM are not included in most HPV vaccination programs. We explored the potential effectiveness of prophylactic immunization in reducing anogenital HPV16 transmission among MSM in the Netherlands.
METHODS AND FINDINGS
We developed a range of mathematical models for penile-anal HPV16 transmission, varying in sexual contact structure and natural history of infection, to provide robust and plausible predictions about the effectiveness of targeted vaccination. Models were informed by an observational cohort study among MSM in Amsterdam, 2010-2013. Parameters on sexual behavior and HPV16 infections were obtained by fitting the models to data from 461 HIV-negative study participants, considered representative of the local MSM population. We assumed 85% efficacy of vaccination against future HPV16 infections as reported for HIV-negative MSM, and age-specific uptake rates similar to those for hepatitis B vaccination among MSM in the Netherlands. Targeted vaccination was contrasted with vaccination of 12-year-old boys at 40% uptake in base-case scenarios, and we also considered the effectiveness of a combined strategy. Offering vaccine to MSM without age restrictions resulted in a model-averaged 27.3% reduction (90% prediction interval [PI] 11.9%-37.5%) in prevalence of anal HPV16 infections, assuming similar uptake among MSM as achieved for hepatitis B vaccination. The predicted reduction improved to 46.1% (90% PI 21.8%-62.4%) if uptake rates among MSM were doubled. The reductions in HPV16 infection prevalence were mostly achieved within 30 years of a targeted immunization campaign, during which they exceeded those induced by vaccinating 40% of preadolescent boys, if started simultaneously. The reduction in anal HPV16 prevalence amounted to 74.8% (90% PI 59.8%-93.0%) under a combined vaccination strategy. HPV16 prevalence reductions mostly exceeded vaccine coverage projections among MSM, illustrating the efficiency of prophylactic immunization even when the HPV vaccine is given after sexual debut. Mode of protection was identified as the key limitation to potential effectiveness of targeted vaccination, as the projected reductions were strongly reduced if we assumed no protection against future infections in recipients with prevalent infection or infection-derived immunity at the time of immunization. Unverified limitations of our study include the sparsity of data to inform the models, the omission of oral sex in transmission to the penile or anal site, and the restriction that our modeling results apply primarily to HIV-negative MSM.
CONCLUSIONS
Our findings suggest that targeted vaccination may generate considerable reductions in anogenital HPV16 infections among MSM, and has the potential to accelerate anal cancer prevention, especially when combined with sex-neutral vaccination in preadolescence.
Identifiants
pubmed: 30830901
doi: 10.1371/journal.pmed.1002756
pii: PMEDICINE-D-18-02579
pmc: PMC6398832
doi:
Substances chimiques
Papillomavirus Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1002756Déclaration de conflit d'intérêts
I have read the journal's policy and the authors of this manuscript have the following competing interests: JAB, SHM and MX declare that they have no conflict of interest. The institution of MFSvdL received study funding from Sanofi Pasteur MSD and Janssen Infectious Diseases and Vaccines; he was a co-investigator in a Merck-funded investigator-initiated study; he was an investigator on a Sanofi Pasteur MSD sponsored trial; he served on a vaccine advisory board of GSK; his institution received in-kind contribution for an HPV study from Stichting Pathologie Onderzoek en Ontwikkeling (SPOO).
Références
Br J Cancer. 2011 Jun 28;105(1):28-37
pubmed: 21629249
Lancet Public Health. 2016 Nov;1(1):e8-e17
pubmed: 29253379
Epidemics. 2017 Dec;21:80-87
pubmed: 28916210
Int J Cancer. 2009 May 15;124(10):2375-83
pubmed: 19189402
Clin Infect Dis. 2018 Oct 15;67(9):1339-1346
pubmed: 29659751
AIDS. 2013 Nov 28;27(18):2921-31
pubmed: 23921617
PLoS Med. 2011 Dec;8(12):e1001147
pubmed: 22205887
PLoS One. 2014 Apr 08;9(4):e93393
pubmed: 24714693
AIDS Care. 2011 Aug;23(8):1014-25
pubmed: 21400315
J Acquir Immune Defic Syndr. 2012 May 1;60(1):83-90
pubmed: 22522237
Lancet Infect Dis. 2010 Dec;10(12):845-52
pubmed: 21051295
Papillomavirus Res. 2016 Dec;2:178-184
pubmed: 29074179
Eur Urol. 2016 May;69(5):953-61
pubmed: 26762611
J Infect Dis. 2017 Aug 1;216(3):336-344
pubmed: 28859431
Lancet Oncol. 2012 May;13(5):487-500
pubmed: 22445259
J Med Screen. 2014 Mar;21(1):38-50
pubmed: 24488594
Sex Transm Infect. 2013 Dec;89(8):666-71
pubmed: 23812794
Future Microbiol. 2014;9(7):837-44
pubmed: 25156373
Clin Infect Dis. 2019 Apr 24;68(9):1556-1565
pubmed: 30169621
Value Health Reg Issues. 2016 Dec;11:17-23
pubmed: 27986194
Lancet Infect Dis. 2015 Jan;15(1):65-73
pubmed: 25435055
Drugs. 2012 Mar 26;72(5):715-43
pubmed: 22413761
BMJ. 2015 May 12;350:h2016
pubmed: 25985328
J Hepatol. 2013 Dec;59(6):1177-83
pubmed: 23954670
Sex Transm Dis. 2002 Nov;29(11):725-35
pubmed: 12438912
Br J Health Psychol. 2017 May;22(2):345-361
pubmed: 28191723
Lancet Infect Dis. 2017 Jan;17(1):68-77
pubmed: 27282422
Clin Infect Dis. 2012 Apr;54(7):891-8
pubmed: 22291111
Lancet Infect Dis. 2011 Jan;11(1):39-44
pubmed: 21067976
Clin Infect Dis. 2017 Mar 1;64(5):580-588
pubmed: 28011615
BMC Infect Dis. 2014 Dec 31;14:668
pubmed: 25551194
Oral Oncol. 2014 May;50(5):364-9
pubmed: 24080455
Nat Rev Cancer. 2018 Apr;18(4):240-254
pubmed: 29497146
Papillomavirus Res. 2016 Dec;2:85-88
pubmed: 29074190
J Infect Dis. 2018 Aug 24;218(7):1018-1026
pubmed: 29771378
N Engl J Med. 2011 Oct 27;365(17):1576-85
pubmed: 22029979
PLoS One. 2015 Jun 19;10(6):e0129877
pubmed: 26090814
J Infect Dis. 2017 Jul 15;216(2):210-219
pubmed: 28586466
N Engl J Med. 2011 Feb 3;364(5):401-11
pubmed: 21288094
MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65(33):850-8
pubmed: 27561081
J Clin Invest. 2011 Dec;121(12):4593-9
pubmed: 22133884
J Infect Dis. 2013 Aug 1;208(3):373-84
pubmed: 23644283
Lancet Oncol. 2018 Mar;19(3):e148
pubmed: 29456089
Int J Cancer. 2018 Nov 1;143(9):2299-2310
pubmed: 29845626
AIDS. 2016 Jan 2;30(1):121-32
pubmed: 26474302
J Acquir Immune Defic Syndr. 2015 Oct 1;70(2):186-94
pubmed: 26102448
Curr HIV/AIDS Rep. 2014 Sep;11(3):250-62
pubmed: 24990810
J Pathol. 1999 Sep;189(1):12-9
pubmed: 10451482
Expert Rev Vaccines. 2018 Dec;17(12):1093-1104
pubmed: 30417704
Vaccine. 2017 Sep 5;35(37):4923-4929
pubmed: 28789853
J Stat Softw. 2010 Aug;36(2):
pubmed: 25285054
AIDS. 2018 Jul 17;32(11):1527-1532
pubmed: 29762169