Opinion statement
The epidemiology of head and neck squamous cell carcinoma (HNSCC) has shifted dramatically over the last 50 years, as smoking-related HNSCCs decrease in incidence while human papillomavirus (HPV)-related cancers rise. The shift in HNSCC risk factors has changed patient demographics, the distribution of affected anatomical subsites, and prognosis of this illness. As such, the medical community has responded by devising novel staging systems and prevention strategies. The medical community will require continued vigilance in reducing HNSCC traditional risks factors for HNSCC, such as cigarette use, and emerging risk like HPV infection.
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References and Recommended Reading
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•• Global Burden of Disease Cancer C, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3(4):524–48 A large comprehensive assessment of the global burden of cancers, including HNSCC.
Simard EP, Torre LA, Jemal A. International trends in head and neck cancer incidence rates: differences by country, sex and anatomic site. Oral Oncol. 2014;50(5):387–403.
• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30 The yearly evaluation of cancer burden in the USA.
Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132(5):1133–45.
Lambert R, Sauvaget C, de Camargo Cancela M, Sankaranarayanan R. Epidemiology of cancer from the oral cavity and oropharynx. Eur J Gastroenterol Hepatol. 2011;23(8):633–41.
DeSantis C, Naishadham D, Jemal A. Cancer statistics for African Americans, 2013. CA Cancer J Clin. 2013;63(3):151–66.
Sankaranarayanan R, Masuyer E, Swaminathan R, Ferlay J, Whelan S. Head and neck cancer: a global perspective on epidemiology and prognosis. Anticancer Res. 1998;18(6B):4779–86.
Pezzuto F, Buonaguro L, Caponigro F, Ionna F, Starita N, Annunziata C, et al. Update on head and neck cancer: current knowledge on epidemiology, risk factors, molecular features and novel therapies. Oncology. 2015;89(3):125–36.
Hashibe M, Brennan P, Benhamou S, Castellsague X, Chen C, Curado MP, et al. Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer Inst. 2007;99(10):777–89.
Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston-Martin S, et al. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res. 1988;48(11):3282–7.
Wyss A, Hashibe M, Chuang SC, Lee YC, Zhang ZF, Yu GP, et al. Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Am J Epidemiol. 2013;178(5):679–90.
Lewin F, Norell SE, Johansson H, Gustavsson P, Wennerberg J, Biorklund A, et al. Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden. Cancer. 1998;82(7):1367–75.
Zhou J, Michaud DS, Langevin SM, McClean MD, Eliot M, Kelsey KT. Smokeless tobacco and risk of head and neck cancer: evidence from a case-control study in New England. Int J Cancer. 2013;132(8):1911–7.
Wyss AB, Hashibe M, Lee YA, Chuang SC, Muscat J, Chen C, et al. Smokeless tobacco use and the risk of head and neck cancer: pooled analysis of US studies in the INHANCE Consortium. Am J Epidemiol. 2016;184(10):703–16.
Kato I, Nomura AM. Alcohol in the aetiology of upper aerodigestive tract cancer. Eur J Cancer B Oral Oncol. 1994;30B(2):75–81.
Murata M, Takayama K, Choi BC, Pak AW. A nested case-control study on alcohol drinking, tobacco smoking, and cancer. Cancer Detect Prev. 1996;20(6):557–65.
Andre K, Schraub S, Mercier M, Bontemps P. Role of alcohol and tobacco in the aetiology of head and neck cancer: a case-control study in the Doubs region of France. Eur J Cancer B Oral Oncol. 1995;31B(5):301–9.
• Voltzke KJ, Lee YA, Zhang ZF, Zevallos JP, Yu GP, Winn DM, et al. Racial differences in the relationship between tobacco, alcohol, and the risk of head and neck cancer: pooled analysis of US studies in the INHANCE Consortium. Cancer Causes Control. 2018. Updated analysis of risk factors for head and neck squamous cell carcinoma;29:619–30.
Stanford-Moore G, Bradshaw PT, Weissler MC, Zevallos JP, Brennan P, Anantharaman D, et al. Interaction between known risk factors for head and neck cancer and socioeconomic status: the Carolina Head and Neck Cancer Study. Cancer Causes Control. 2018;29(9):863–73.
•• O’Sullivan B, Huang SH, Su J, Garden AS, Sturgis EM, Dahlstrom K, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol. 2016;17(4):440–51 A large, multi-center study used to create the 8th edition TNM staging system for oropharynx cancer.
Vokes EE, Agrawal N, Seiwert TY. HPV-associated head and neck cancer. J Natl Cancer Inst. 2015;107(12):djv344.
Guha N, Warnakulasuriya S, Vlaanderen J, Straif K. Betel quid chewing and the risk of oral and oropharyngeal cancers: a meta-analysis with implications for cancer control. Int J Cancer. 2014;135(6):1433–43.
Hu YJ, Chen J, Zhong WS, Ling TY, Jian XC, Lu RH, et al. Trend analysis of betel nut-associated oral cancer and health burden in China. Chin J Dent Res. 2017;20(2):69–78.
Guha N, Boffetta P, Wunsch Filho V, Eluf Neto J, Shangina O, Zaridze D, et al. Oral health and risk of squamous cell carcinoma of the head and neck and esophagus: results of two multicentric case-control studies. Am J Epidemiol. 2007;166(10):1159–73.
Mazul AL, Taylor JM, Divaris K, Weissler MC, Brennan P, Anantharaman D, et al. Oral health and human papillomavirus-associated head and neck squamous cell carcinoma. Cancer. 2017;123(1):71–80.
Economides MP, Amit M, Mahale PS, Hosry JJ, Jiang Y, Bharadwaj U, et al. Impact of chronic hepatitis C virus infection on the survival of patients with oropharyngeal cancer. Cancer. 2018;124(5):960–5.
Mahale P, Sturgis EM, Tweardy DJ, Ariza-Heredia EJ, Torres HA. Association between hepatitis C virus and head and neck cancers. J Natl Cancer Inst. 2016;108(8):djw035.
D’Souza G, Carey TE, William WN Jr, Nguyen ML, Ko EC, Riddell JT, et al. Epidemiology of head and neck squamous cell cancer among HIV-infected patients. J Acquir Immune Defic Syndr. 2014;65(5):603–10.
Liu Q, Yan L, Xu C, Gu A, Zhao P, Jiang ZY. Increased incidence of head and neck cancer in liver transplant recipients: a meta-analysis. BMC Cancer. 2014;14:776.
Rabinovics N, Mizrachi A, Hadar T, Ad-El D, Feinmesser R, Guttman D, et al. Cancer of the head and neck region in solid organ transplant recipients. Head Neck. 2014;36(2):181–6.
Vigneswaran N, Williams MD. Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am. 2014;26(2):123–41.
Vukovic V, Stojanovic J, Vecchioni A, Pastorino R, Boccia S. Systematic review and meta-analysis of SNPs from genome-wide association studies of head and neck cancer. Otolaryngol Head Neck Surg. 2018;159(4):615–24.
Snijders PJ, Cromme FV, van den Brule AJ, Schrijnemakers HF, Snow GB, Meijer CJ, et al. Prevalence and expression of human papillomavirus in tonsillar carcinomas, indicating a possible viral etiology. Int J Cancer. 1992;51(6):845–50.
Haraf DJ, Nodzenski E, Brachman D, Mick R, Montag A, Graves D, et al. Human papilloma virus and p53 in head and neck cancer: clinical correlates and survival. Clin Cancer Res. 1996;2(4):755–62.
Palefsky JM, Holly EA. Molecular virology and epidemiology of human papillomavirus and cervical cancer. Cancer Epidemiol Biomark Prev. 1995;4(4):415–28.
Gillison ML, Broutian T, Pickard RK, Tong ZY, Xiao W, Kahle L, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 2012;307(7):693–703.
Trottier H, Mayrand MH, Coutlee F, Monnier P, Laporte L, Niyibizi J, et al. Human papillomavirus (HPV) perinatal transmission and risk of HPV persistence among children: design, methods and preliminary results of the HERITAGE study. Papillomavirus Res. 2016;2:145–52.
• de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017;141(4):664–70 A large epidemiologic study evaluating the role of HPV in global cancer burden.
Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer--systematic review and meta-analysis of trends by time and region. Head Neck. 2013;35(5):747–55.
Mourad M, Jetmore T, Jategaonkar AA, Moubayed S, Moshier E, Urken ML. Epidemiological trends of head and neck cancer in the United States: a SEER population study. J Oral Maxillofac Surg. 2017;75(12):2562–72.
Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294–301.
Liederbach E, Kyrillos A, Wang CH, Liu JC, Sturgis EM, Bhayani MK. The national landscape of human papillomavirus-associated oropharynx squamous cell carcinoma. Int J Cancer. 2017;140(3):504–12.
Rettig EM, Zaidi M, Faraji F, Eisele DW, El Asmar M, Fung N, et al. Oropharyngeal cancer is no longer a disease of younger patients and the prognostic advantage of human papillomavirus is attenuated among older patients: analysis of the National Cancer Database. Oral Oncol. 2018;83:147–53.
Sonawane K, Suk R, Chiao EY, Chhatwal J, Qiu P, Wilkin T, et al. Oral human papillomavirus infection: differences in prevalence between sexes and concordance with genital human papillomavirus infection, NHANES 2011 to 2014. Ann Intern Med. 2017;167(10):714–24.
Berenson AB, Hirth JM, Chang M. Change in human papillomavirus prevalence among U.S. women aged 18-59 years, 2009-2014. Obstet Gynecol. 2017;130(4):693–701.
Anantharaman D, Abedi-Ardekani B, Beachler DC, Gheit T, Olshan AF, Wisniewski K, et al. Geographic heterogeneity in the prevalence of human papillomavirus in head and neck cancer. Int J Cancer. 2017;140(9):1968–75.
Ndiaye C, Mena M, Alemany L, Arbyn M, Castellsague X, Laporte L, et al. HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. Lancet Oncol. 2014;15(12):1319–31.
Mehanna H, Franklin N, Compton N, Robinson M, Powell N, Biswas-Baldwin N, et al. Geographic variation in human papillomavirus-related oropharyngeal cancer: data from 4 multinational randomized trials. Head Neck. 2016;38(Suppl 1):E1863–9.
Chan MH, Wang F, Mang WK, Tse LA. Sex differences in time trends on incidence rates of oropharyngeal and oral cavity cancers in Hong Kong. Ann Otol Rhinol Laryngol. 2018;127(12):895–902.
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.
Negri E, La Vecchia C, Franceschi S, Tavani A. Attributable risk for oral cancer in northern Italy. Cancer Epidemiol Biomark Prev. 1993;2(3):189–93.
Kim L, King T, Agulnik M. Head and neck cancer: changing epidemiology and public health implications. Oncology (Williston Park). 2010;24(10):915–24.
Phillips E, Wang TW, Husten CG, Corey CG, Apelberg BJ, Jamal A, et al. Tobacco product use among adults - United States, 2015. MMWR Morb Mortal Wkly Rep. 2017;66(44):1209–15.
Kasza KA, Ambrose BK, Conway KP, Borek N, Taylor K, Goniewicz ML, et al. Tobacco-product use by adults and youths in the United States in 2013 and 2014. N Engl J Med. 2017;376(4):342–53.
Zatonski W, Przewozniak K, Sulkowska U, West R, Wojtyla A. Tobacco smoking in countries of the European Union. Ann Agric Environ Med. 2012;19(2):181–92.
Mifsud M, Eskander A, Irish J, Gullane P, Gilbert R, Brown D, et al. Evolving trends in head and neck cancer epidemiology: Ontario, Canada 1993-2010. Head Neck. 2017;39(9):1770–8.
Marcon A, Pesce G, Calciano L, Bellisario V, Dharmage SC, Garcia-Aymerich J, et al. Trends in smoking initiation in Europe over 40 years: a retrospective cohort study. PLoS One. 2018;13(8):e0201881.
Peacock A, Leung J, Larney S, Colledge S, Hickman M, Rehm J, et al. Global statistics on alcohol, tobacco and illicit drug use: 2017 status report. Addiction. 2018;113(10):1905–26.
Huang SH, Xu W, Waldron J, Siu L, Shen X, Tong L, et al. Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas. J Clin Oncol. 2015;33(8):836–45.
Dahlstrom KR, Garden AS, William WN Jr, Lim MY, Sturgis EM. Proposed staging system for patients with HPV-related oropharyngeal cancer based on nasopharyngeal cancer N categories. J Clin Oncol. 2016;34(16):1848–54.
Malm IJ, Fan CJ, Yin LX, Li DX, Koch WM, Gourin CG, et al. Evaluation of proposed staging systems for human papillomavirus-related oropharyngeal squamous cell carcinoma. Cancer. 2017;123(10):1768–77.
•• Haughey BH, Sinha P, Kallogjeri D, Goldberg RL, Lewis JS Jr, Piccirillo JF, et al. Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx. Oral Oncol. 2016;62:11–9 A large multicenter study used to establish the surgical TNM staging for 8th edition.
Amin MB, American Joint Committee on Cancer, American Cancer Society. AJCC cancer staging manual. Eight edition / editor-in-chief, Mahul B. Amin, MD, FCAP ; editors, Stephen B. Edge, MD, FACS and 16 others ; Donna M. Gress, RHIT, CTR - Technical editor ; Laura R. Meyer, CAPM - Managing editor. ed. Chicago IL: American Joint Committee on Cancer, Springer; 2017. xvii, 1024 pages p.
Chung CH, Zhang Q, Kong CS, Harris J, Fertig EJ, Harari PM, et al. p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma. J Clin Oncol. 2014;32(35):3930–8.
Fakhry C, Westra WH, Wang SJ, van Zante A, Zhang Y, Rettig E, et al. The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer. Cancer. 2017;123(9):1566–75.
zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2(5):342–50.
Van Dyne EA, Henley SJ, Saraiya M, Thomas CC, Markowitz LE, Benard VB. Trends in human papillomavirus-associated cancers - United States, 1999-2015. MMWR Morb Mortal Wkly Rep. 2018;67(33):918–24.
Munoz N, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, et al. Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women. J Natl Cancer Inst. 2010;102(5):325–39.
Lehtinen M, Paavonen J, Wheeler CM, Jaisamrarn U, Garland SM, Castellsague X, et al. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012;13(1):89–99.
Palefsky JM, Giuliano AR, Goldstone S, Moreira ED Jr, Aranda C, Jessen H, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med. 2011;365(17):1576–85.
Ahn J, Peng S, Hung CF, Roden RBS, Best SR. Prophylactic immunization with human papillomavirus vaccines induces oral immunity in mice. Laryngoscope. 2018;128(1):E16–20.
Handisurya A, Schellenbacher C, Haitel A, Senger T, Kirnbauer R. Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids. Br J Cancer. 2016;114(4):409–16.
Herrero R, Wacholder S, Rodriguez AC, Solomon D, Gonzalez P, Kreimer AR, et al. Prevention of persistent human papillomavirus infection by an HPV16/18 vaccine: a community-based randomized clinical trial in Guanacaste, Costa Rica. Cancer Discov. 2011;1(5):408–19.
Walker TY, Elam-Evans LD, Yankey D, Markowitz LE, Williams CL, Mbaeyi SA, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years - United States, 2017. MMWR Morb Mortal Wkly Rep. 2018;67(33):909–17.
FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old [Available from: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm622715.htm.
Human papillomavirus (HPV) vaccination coverage in adolescent females in England: 2016/17 [Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/666087/HPV_vaccination_coverage_in_adolescent_females_in_England_2016_to_2017.pdf.
National (Australia) HPV 3 dose vaccination coverage for adolescents turning 15 years of age [Available from: http://www.hpvregister.org.au/research/coverage-data. Accessed 4 Apr 2019.
Giuliano AR, Nyitray AG, Kreimer AR, Pierce Campbell CM, Goodman MT, Sudenga SL, et al. EUROGIN 2014 roadmap: differences in human papillomavirus infection natural history, transmission and human papillomavirus-related cancer incidence by gender and anatomic site of infection. Int J Cancer. 2015;136(12):2752–60.
Roteli-Martins CM, Naud P, De Borba P, Teixeira JC, De Carvalho NS, Zahaf T, et al. Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up. Hum Vaccin Immunother. 2012;8(3):390–7.
Primack BA, Shensa A, Sidani JE, Hoffman BL, Soneji S, Sargent JD, et al. Initiation of traditional cigarette smoking after electronic cigarette use among tobacco-naive US young adults. Am J Med. 2018;131(4):443 e1–9.
McQueen N, Partington EJ, Harrington KF, Rosenthal EL, Carroll WR, Schmalbach CE. Smoking cessation and electronic cigarette use among head and neck cancer patients. Otolaryngol Head Neck Surg. 2016;154(1):73–9.
Hartmann-Boyce J, McRobbie H, Bullen C, Begh R, Stead LF, Hajek P. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2016;9:CD010216.
Yu V, Rahimy M, Korrapati A, Xuan Y, Zou AE, Krishnan AR, et al. Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Oral Oncol. 2016;52:58–65.
FDA seeks tighter restrictions on E-cigarettes. Cancer Discov. 2019;9(1):OF3. https://doi.org/10.1158/2159-8290.CD-NB2018-158.
Gupta PC, Warnakulasuriya S. Global epidemiology of areca nut usage. Addict Biol. 2002;7(1):77–83.
Mehrtash H, Duncan K, Parascandola M, David A, Gritz ER, Gupta PC, et al. Defining a global research and policy agenda for betel quid and areca nut. Lancet Oncol. 2017;18(12):e767–e75.
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McDermott, J.D., Bowles, D.W. Epidemiology of Head and Neck Squamous Cell Carcinomas: Impact on Staging and Prevention Strategies. Curr. Treat. Options in Oncol. 20, 43 (2019). https://doi.org/10.1007/s11864-019-0650-5
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DOI: https://doi.org/10.1007/s11864-019-0650-5