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HPV vaccination in boys should not be discounted

Thursday, 19th of January 2017

The Lancet Public Health, Volume 1, No. 1, e2–e3, November 2016

HPV vaccination in boys should not be discounted

Samantha Tam et al.

Elsevier open access license policy

© 2016 The Author(s). Published by Elsevier Ltd.

In The Lancet Public Health, Marc Brisson and colleagues1x1Brisson, M, Benard, É, Drolet, M et al. Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models. Lancet Public Health. 2016; (published online Sept 27.)http://dx.doi.org/10.1016/S2468-2667(16)30001-9.

1 report pooled results from multiple mathematical models to predict the effect of human papillomavirus (HPV) vaccination on HPV infections. A unified input dataset was used to obtain results from 16 models that were combined using meta-analysis, yielding interesting findings about the dynamics of vaccination in girls and boys. Models such as those included in this study have become increasingly important to inform policy makers about predicted effects of interventions as well as other endpoints, such as cost, and the authors should be commended for their approach.

One major finding of this paper is that a high rate of HPV vaccination in girls confers adequate protection of boys through herd immunity. For example, for men, predicted overall prevalence of HPV 16 decreased by 36% (80% uncertainty interval 28–61) after 70 years of girls-only vaccination assuming 40% coverage, and by 83% (75–100) assuming 80% coverage. Notably, elimination of viral prevalence in boys, especially for HPV 16, was not achieved with this girls-only strategy. In view of the substantial herd effects of girls-only vaccination when coverage is moderate to high, the authors conclude that the incremental benefit of vaccinating boys is predicted to be small. Such conclusions could focus policy makers away from vaccination programmes targeting boys. However, HPV-related cancers have become an increasingly important issue for men in high-income countries.

HPV is thought to cause about 91% of anal cancers, 72% of oropharyngeal cancers, and 63% of penile cancers in the USA.2x2Saraiya, M, Unger, ER, Thompson, TD et al. US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines. J Natl Cancer Insti. 2015; 107: djv086

 |  |  (38), 3x3Chaturvedi, AK, Engels, EA, Pfeiffer, RM et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011; 29: 4294–4301

 |  |  (961) The vast majority of HPV-related cancers in men are attributable to type 16.4x4Kreimer, AR, Clifford, GM, Boyle, P, and Franceschi, S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005; 14: 467–475

 |  |  (1065), 5x5De Vuyst, H, Clifford, GM, Nascimento, MC, Madeleine, MM, and Franceschi, S. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer. 2009; 124: 1626–1636

 |  |  (431) Oropharyngeal cancers specifically have caused a substantial shift in the landscape of HPV-related cancers. Oropharyngeal carcinoma is approximately five times more common in middle-aged men than in middle-aged women.6x6Viens, LJ, Henley, SJ, Watson, M et al. Human papillomavirus-associated cancers—United States, 2008–2012. MMWR Morb Mortal Wkly Rep. 2016; 65: 661–666

 | 6 Incidence has been increasing at an alarming, even epidemic, rate, with an increase of 225% between 1988 and 2004 in the USA (from 0·8 cases per 100 000 people in 1988, to 2·6 cases per 100 000 people in 2004).3x3Chaturvedi, AK, Engels, EA, Pfeiffer, RM et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011; 29: 4294–4301

 |  |  (961)3 Meanwhile, comprehensive screening programmes have been successful in decreasing the incidence of cervical cancer in high-income countries. In 2010, incidence of oropharyngeal cancer overtook that of cervical cancer in the USA.3x3Chaturvedi, AK, Engels, EA, Pfeiffer, RM et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011; 29: 4294–4301

 |  |  (961)3 Furthermore, it is predicted that cases of HPV-related oropharyngeal cancer will surpass all cases of cervical cancer in 4 years, with more recent evidence suggesting that this might have already occurred in the USA.3x3Chaturvedi, AK, Engels, EA, Pfeiffer, RM et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011; 29: 4294–4301

 |  |  (961), 6x6Viens, LJ, Henley, SJ, Watson, M et al. Human papillomavirus-associated cancers—United States, 2008–2012. MMWR Morb Mortal Wkly Rep. 2016; 65: 661–666

 |

Unfortunately, unlike with Pap and HPV testing of the cervix, no effective screening measures are available for oropharyngeal cancer. As such, patients often present with late-stage disease, requiring extensive multimodality treatment, which often results in long-term morbidity.7x7Dahlstrom, KR, Calzada, G, Hanby, JD et al. An evolution in demographics, treatment, and outcomes of oropharyngeal cancer at a major cancer center: a staging system in need of repair. Cancer. 2013; 119: 81–89

 |  |  (45)7 Without any method of early detection of HPV-related oropharyngeal cancer in men, the importance of primary prevention through the vaccination of boys is further emphasised.

The cost of treating patients with oropharyngeal cancer has also been underestimated in the scientific literature. Costs for oropharyngeal cancers are often pooled with costs for oral cavity or salivary cancers, whose treatment and long-term outcomes, and hence costs, are on average much lower than that of oropharyngeal cancers.8x8Hu, D and Goldie, S. The economic burden of noncervical human papillomavirus disease in the United States. Am J Obstet Gynecol. 2008; 198: 500 (e1–7.)

Summary | Full Text |  |  |  (91), 9x9Jacobson, JJ, Epstein, JB, Eichmiller, FC et al. The cost burden of oral, oral pharyngeal, and salivary gland cancers in three groups: commercial insurance, Medicare, and Medicaid. Head Neck Oncol. 2012; 4: 15

 |  |  (23) Because most patients present with advanced disease, multimodality therapy is almost always required, substantially increasing health-care use and cost. Our group is currently investigating the cost of treating oropharyngeal cancer in Texas, USA, specifically omitting cancers of other head and neck sites. Our preliminary findings suggest that the true cost of oropharyngeal cancer treatment greatly exceeds the costs currently reported in the literature.

This changing landscape of HPV-related cancers is an essential factor that needs to inform policy on HPV vaccination programmes. Although programmes have traditionally focused on vaccination of girls, the importance of vaccination of boys needs to be addressed, especially as oropharyngeal cancer comes to the forefront of HPV-related cancers in high-income countries. This shift is particularly essential in countries where vaccination rates in both girls and boys are low, such as the USA, where only about 42% of girls and 28% of boys completed the government recommended schedule for HPV vaccination in 2015.10x10Reagan-Steiner, S, Yankey, D, Jeyarajah, J et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13–17 years—United States, 2015. MMWR Morb Mortal Wkly Rep. 2016; 65: 850–858

 | 10 It is essential not to diminish the importance of vaccination of boys, especially considering the increasing representation of men in the HPV-related cancer burden, substantial costs of treatment, and lack of screening for early detection of disease.

We declare no competing interests. We acknowledge funding contributions from the Christopher and Susan Damico Chair in Viral Associated Malignancies, the Stiefel Oropharyngeal Research Fund, and The University of Texas MD Anderson Moon Shots Program.

References

1Brisson, M, Benard, É, Drolet, M et al. Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models. Lancet Public Health. 2016; (published online Sept 27.)http://dx.doi.org/10.1016/S2468-2667(16)30001-9.View in Article 

2Saraiya, M, Unger, ER, Thompson, TD et al. US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines. J Natl Cancer Insti. 2015; 107: djv086

3Chaturvedi, AK, Engels, EA, Pfeiffer, RM et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011; 29: 4294–4301

4Kreimer, AR, Clifford, GM, Boyle, P, and Franceschi, S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005; 14: 467–475

5De Vuyst, H, Clifford, GM, Nascimento, MC, Madeleine, MM, and Franceschi, S. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer. 2009; 124: 1626–1636

6Viens, LJ, Henley, SJ, Watson, M et al. Human papillomavirus-associated cancers—United States, 2008–2012. MMWR Morb Mortal Wkly Rep. 2016; 65: 661–666

7Dahlstrom, KR, Calzada, G, Hanby, JD et al. An evolution in demographics, treatment, and outcomes of oropharyngeal cancer at a major cancer center: a staging system in need of repair. Cancer. 2013; 119: 81–89

8Hu, D and Goldie, S. The economic burden of noncervical human papillomavirus disease in the United States. Am J Obstet Gynecol. 2008; 198: 500 (e1–7.)

9Jacobson, JJ, Epstein, JB, Eichmiller, FC et al. The cost burden of oral, oral pharyngeal, and salivary gland cancers in three groups: commercial insurance, Medicare, and Medicaid. Head Neck Oncol. 2012; 4: 15

10Reagan-Steiner, S, Yankey, D, Jeyarajah, J et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13–17 years—United States, 2015. MMWR Morb Mortal Wkly Rep. 2016; 65: 850–858