STI Online First, published on April 21, 2015 as 10.1136/sextrans-2014-051808 Editorial Sex Transm Infect: first published as 10.1136/sextrans-2014-051808 on 21 April 2015. Downloaded from

and penile carcinogenesis are also increas- Exploring the implications of HPV ingly well described, with >80% of anal cancers21 and around 40% of penile infection for cancers being HPV-associated. However, for oropharyngeal cancers, the equivalent 1 2 Nigel Field, Matt Lechner precancerous lesions have yet to be defined. Good understanding of the transi- tion from a transient to persistent HPV Over recent years, human papillomavirus people reporting oral sex in the past year infection and then to cancer is also (HPV) has been shown to be a major risk occurred between 1990 and 2000, and lacking, and a biomarker that would factor for head and neck squamous cell this proportion remained high between enable risk assessment of lesions to distin- cancer (HNSCC), and particularly oro- 2000 and 2010.14 Similarly, around 75% 12 guish malignancy potential does not exist. pharyngeal . of men and 65% of women born between There is increasing evidence that the risk In 2007, the International Agency for 1946 and 1955 reported ever giving or of HPV-associated malignancies, such as Research on Cancer recognised HPV as a receiving oral sex, but this proportion was anal and , is higher in carcinogen associated with malignant over 90% among men and women born HIV-infected individuals and men who transformation in this subset of head and 20 years later. That oral sex is an almost have sex with men (MSM).22 If the risk of neck cancers. It is now well established ubiquitous exposure probably explains HNSCC is similarly increased in these that HPV-induced oropharyngeal cancers why some of the largest and methodo- groups (and a recent study has shown a and those caused by other factors (such as logically most robust studies have failed to higher incidence of HPV-associated — fi smoking and alcohol abuse a combin- nd an association between reporting oral HNSCCs among HIV-positive indivi- ation of heavy smoking and drinking sex and the detection of oral HPV infec- duals23), these groups may stand to benefit leads to an almost 50-fold increased risk tion.15 However, much remains to be 3 most from any screening programme. of oral and pharyngeal cancer ) are two understood about the acquisition and per- Although the effectiveness of HPV vac- separate entities, with distinct aetiologies, sistence of oral HPV infection, and the cination to protect against head and neck clinical characteristics, prognoses and a evidence for changes in sexual behaviour cancers is not yet proven, in some case different epidemiology and molecular driving increases in HPV-associated 4 series >70% of oropharyngeal cancers test basis. HNSCCs is still circumstantial. positive for high-risk HPV type-16.1 The incidence of HPV-associated The increase in HPV-induced HNSCC Immunisation against oncogenic HPV sub- HNSCC has risen rapidly in the Western has important clinical implications because 5–8 types, introduced in the UK for girls in world over the past 40 years. For this subset of cancers responds better to 2008, is likely to transform the epidemi- example, there has been an estimated chemotherapy and radiotherapy (82% vs ology of all HPV-associated cancers in the threefold increase in tonsillar cancer 55% response rate for HPV-negative cases) UK and in other countries where it has during this period,9 and the overall esti- and has a better disease-free and overall 16 been introduced. Dramatic changes in the mated population-level incidence of survival (95% vs 62% at 2 years). incidence of HPV-associated cancers are HPV-positive oropharyngeal cancer, Patients with HPV-induced HNSCC have therefore to be expected. There are also which was 2.6 per 100 000 in the USA in a lower incidence of second primary 6 several proposed changes to vaccination 2004, is set to triple again in the next tumours, as well as decreased risk (or http://sti.bmj.com/ 10 17 18 programmes that may further affect the 20 years. Interestingly, the overall inci- cumulative incidence) of relapse. incidence of HPV-associated cancers. A dence of HNSCC is falling at a time when In the same way that HPV testing has nonavalent vaccine is currently in clinical the incidence of HPV-induced cancer has been incorporated into the trials, which would protect against high-risk risen, with the result that the proportion screening programme for samples with HPV types not included in the current vac- of HPV-positive tonsillar cases has risen borderline or mild dyskaryosis to inform cines ( and protect against from <25% in the 1970s to 93% of cases clinical management,19 there is now inter- 7 HPV 16 and 18 and not HPV 31 and 33). on September 29, 2021 by guest. Protected copyright. by 2007 in parts of the developed world. est in developing a valid and reliable test to In the UK, the decision not to vaccinate It is also noteworthy that those affected determine the HPV status of oropharyn- boys is being revisited by the Joint fi tend to be younger patients (age geal tumours. This may enable risk strati - Committee on Vaccination and <50 years) who are frequently non- cation of patients to inform treatment Immunisation, in part due to increasing evi- smokers, and that men seem to be at decisions, as well as further elucidating the dence about the role of HPV in anal, higher risk of developing this type of molecular virology and mechanisms 11 penile, head and neck, and other cancers, cancer than women. underlying the advantage in drug response and in part due to the lack of herd protec- There is good evidence for sexual and survival seen in HPV-associated tion afforded to MSM. However, indivi- acquisition of oropharyngeal HPV infec- HNSCC. In order to do this, one needs to 12 13 duals currently infected with high-risk HPV tion, and an intriguing hypothesis is better understand how HPV-induced oro- in the oropharynx and the vast majority of that the increase in HPV-associated pharyngeal cancers evolve. It is well estab- the global population who have not been HNSCC might be driven in part and pre- lished that cervical cancer develops vaccinated remain at risk of developing dated by changes in population sexual through increasingly severe grades of neo- HPV-associated head and neck cancer. behaviour. In the UK, for example, a sig- plasia, and understanding of the sequence nificant increase in the proportion of of molecular changes underlying these Contributors This work was conceived and written events has supported implementation of jointly by NF and ML.

1 screening programmes, which in turn have Competing interests None. Research Department of Infection & Population Health, fi 2 signi cantly reduced the mortality of cer- Provenance and peer review Commissioned; University College London, London, UK; UCL Cancer 20 Institute, University College London, London, UK vical cancer in the Western world. Anal internally peer reviewed.

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3 Rodriguez T, Altieri A, Chatenoud L, et al. Risk papillomavirus infection. J Infect Dis factors for oral and pharyngeal cancer in young 2009;199:1263–9. adults. Oral Oncol 2004;40:207–13. 14 Mercer CH, Tanton C, Prah P, et al. Changes in 4 Gillison ML. Human papillomavirus-associated head sexual attitudes and lifestyles in Britain through the and neck cancer is a distinct epidemiologic, clinical, life course and over time: findings from the National and molecular entity. Semin Oncol 2004;31:744–54. Surveys of Sexual Attitudes and Lifestyles (Natsal). 5 Chaturvedi AK, Engels EA, Anderson WF, et al. Lancet 2013;382:1781–94. Open Access This is an Open Access article Incidence trends for human papillomavirus-related 15 Kreimer AR, Pierce Campbell CM, Lin H-Y, et al. distributed in accordance with the Creative Commons and -unrelated oral squamous cell carcinomas in the Incidence and clearance of oral human Attribution Non Commercial (CC BY-NC 4.0) license, United States. J Clin Oncol 2008;26:612–19. papillomavirus infection in men: the HIM cohort which permits others to distribute, remix, adapt, build 6 Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human study. Lancet 2013;382:877–87. upon this work non-commercially, and license their papillomavirus and rising oropharyngeal cancer 16 Fakhry C, Westra WH, Li S, et al. Improved survival derivative works on different terms, provided the incidence in the United States. J Clin Oncol of patients with human papillomavirus-positive head original work is properly cited and the use is non- 2011;29:4294–301. and neck squamous cell carcinoma in a prospective commercial. See: http://creativecommons.org/licenses/ 7 Nasman A, Attner P, Hammarstedt L, et al. Incidence clinical trial. J Natl Cancer Inst 2008;100:261–9. by-nc/4.0/ of human papillomavirus (HPV) positive tonsillar 17 Licitra L, Perrone F, Bossi P, et al. High-risk human To cite Field N, Lechner M. Sex Transm Infect carcinoma in Stockholm, Sweden: an epidemic of papillomavirus affects prognosis in patients with Published Online First: [please include Day Month Year] viral-induced carcinoma? Int J Cancer surgically treated oropharyngeal squamous cell doi:10.1136/sextrans-2014-051808 2009;125:362–6. carcinoma. J Clin Oncol 2006;24:5630–6. 8 Garnaes E, Kiss K, Andersen L, et al. A high and 18 Hafkamp HC, Manni JJ, Haesevoets A, et al. Marked Accepted 19 November 2014 increasing HPV prevalence in tonsillar cancers in differences in survival rate between smokers and Eastern Denmark, 2000–2010: the largest nonsmokers with HPV 16-associated tonsillar registry-based study to date. Int J Cancer Published carcinomas. Int J Cancer 2008;122:2656–64. Online First: 4 Oct 2014. 19 England D.o.P.H., NHS Cervical Screening 9 Marur S, D’Souza G, Westra WH, et al. Programme. ▸ http://dx.doi.org/10.1136/sextrans-2014-051955 HPV-associated head and neck cancer: a virus-related 20 Peirson L, Fitzpatrick-Lewis D, Ciliska D, et al. cancer epidemic. Lancet Oncol 2010;11:781–9. Screening for cervical cancer: a systematic review and 10 Pytynia KB, Dahlstrom KR, Sturgis EM. Epidemiology meta-analysis. Syst Rev 2013;2:35. – Sex Transm Infect 2014;0:1 2. of HPV-associated oropharyngeal cancer. Oral Oncol 21 Frisch M, Glimelius B, van den Brule AJC, et al. doi:10.1136/sextrans-2014-051808 2014;50:380–6. Sexually transmitted infection as a cause of anal 11 Gillespie MB, Rubinchik S, Hoel B, et al. Human cancer. N Engl J Med 1997;337:1350–8. papillomavirus and oropharyngeal cancer: what you 22 Palefsky JM. Human papillomavirus-related disease need to know in 2009. Curr Treat Options Oncol in men: not just a women’s issue. J Adolesc Health REFERENCES 2009;10:296–307. 2010;46(4 Suppl):S12–19. 1D’Souza G, Kreimer AR, Viscidi R, et al. Case-control 12 Kreimer AR, Alberg AJ, Daniel R, et al. Oral human 23 Beachler DC, Abraham AG, Silverberg MJ, et al. study of human papillomavirus and oropharyngeal papillomavirus infection in adults is associated with Incidence and risk factors of HPV-related and cancer. N Engl J Med 2007;356:1944–56. sexual behavior and HIV serostatus. J Infect Dis HPV-unrelated Head and Neck Squamous Cell 2 Tran N, Rose BR, O’Brien CJ. Role of human 2004;189:686–98. Carcinoma in HIV-infected individuals. Oral Oncol papillomavirus in the etiology of head and neck 13 D’Souza G, Agrawal Y, Halpern J, et al. Oral sexual Published Online First: 6 Oct 2014. cancer. Head Neck 2007;29:64–70. behaviors associated with prevalent oral human http://sti.bmj.com/ on September 29, 2021 by guest. Protected copyright.

2 Field N, et al. Sex Transm Infect Month 2014 Vol 0 No 0