Epidemiology and risk factors for head and neck cancer
- Kerstin M Stenson, MD, FACS
Kerstin M Stenson, MD, FACS
- Professor of Otolaryngology
- Chief, Head and Neck Cancer Program, Rush University Medical Center
- Department of Otolaryngology/Head and Neck Surgery
Head and neck cancer is common in several regions of the world. The primary risk factors associated with head and neck cancer include tobacco use, alcohol consumption, human papillomavirus (HPV) infection (for oropharyngeal cancer), and Epstein-Barr virus (EBV) infection (for nasopharyngeal cancer). The chronic exposure of the upper aerodigestive tract to these carcinogenic factors can result in dysplastic or premalignant lesions in the oropharyngeal mucosa and ultimately result in head and neck cancer. The relative prevalence of these risk factors contributes to the variations in the observed distribution of head and neck cancer in different areas of the world.
The epidemiology of head and neck cancer and the risk factors for and pathogenesis of these tumors will be reviewed here. Issues related to pathology, diagnosis, staging, and therapy are considered separately. (See appropriate topic reviews.)
Worldwide, head and neck cancer accounts for more than 550,000 cases and 380,000 deaths annually . In the United States, head and neck cancer accounts for 3 percent of malignancies, with approximately 63,000 Americans developing head and neck cancer annually and 13,000 dying from the disease . In Europe, there were approximately 250,000 cases (estimated 4 percent of the cancer incidence) and 63,500 deaths in 2012 .
Males are affected significantly more than females with a ratio ranging from 2:1 to 4:1. The incidence rate in males exceeds 20 per 100,000 in regions of France, Hong Kong, the Indian subcontinent, central and eastern Europe, Spain, Italy, Brazil, and among African Americans in the United States. Mouth and tongue cancers are more common in the Indian subcontinent; nasopharyngeal cancer is more common in Hong Kong; and pharyngeal and/or laryngeal cancers are more common in other populations; these factors contribute disproportionately to the overall cancer burden in these Asian countries [4,5].
The incidence of laryngeal cancer, but not oral cavity and pharyngeal cancer, is approximately 50 percent higher in African American men . The mortality associate with both laryngeal and oropharyngeal cancer is significantly higher in African American men, which may reflect the lower prevalence of human papillomavirus (HPV) positivity . (See "Human papillomavirus associated head and neck cancer", section on 'TNM staging system'.)
- Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, 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 2016.
- Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
- Gatta G, Botta L, Sanchez MJ, et al. Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 population-based study. Eur J Cancer 2015; 51:2130.
- 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; 132:1133.
- Lambert R, Sauvaget C, de Camargo Cancela M, Sankaranarayanan R. Epidemiology of cancer from the oral cavity and oropharynx. Eur J Gastroenterol Hepatol 2011; 23:633.
- DeSantis C, Naishadham D, Jemal A. Cancer statistics for African Americans, 2013. CA Cancer J Clin 2013; 63:151.
- Settle K, Posner MR, Schumaker LM, et al. Racial survival disparity in head and neck cancer results from low prevalence of human papillomavirus infection in black oropharyngeal cancer patients. Cancer Prev Res (Phila) 2009; 2:776.
- Sankaranarayanan R, Masuyer E, Swaminathan R, et al. Head and neck cancer: a global perspective on epidemiology and prognosis. Anticancer Res 1998; 18:4779.
- Wyss A, Hashibe M, Chuang SC, 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; 178:679.
- Blot WJ, McLaughlin JK, Winn DM, et al. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 1988; 48:3282.
- Spitz MR. Epidemiology and risk factors for head and neck cancer. Semin Oncol 1994; 21:281.
- Lewin F, Norell SE, Johansson H, 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; 82:1367.
- 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:301.
- Proia NK, Paszkiewicz GM, Nasca MA, et al. Smoking and smokeless tobacco-associated human buccal cell mutations and their association with oral cancer--a review. Cancer Epidemiol Biomarkers Prev 2006; 15:1061.
- Sapkota A, Gajalakshmi V, Jetly DH, et al. Smokeless tobacco and increased risk of hypopharyngeal and laryngeal cancers: a multicentric case-control study from India. Int J Cancer 2007; 121:1793.
- Rosenquist K, Wennerberg J, Schildt EB, et al. Use of Swedish moist snuff, smoking and alcohol consumption in the aetiology of oral and oropharyngeal squamous cell carcinoma. A population-based case-control study in southern Sweden. Acta Otolaryngol 2005; 125:991.
- Znaor A, Brennan P, Gajalakshmi V, et al. Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men. Int J Cancer 2003; 105:681.
- Tan EH, Adelstein DJ, Droughton ML, et al. Squamous cell head and neck cancer in nonsmokers. Am J Clin Oncol 1997; 20:146.
- Wyss AB, Hashibe M, Lee YA, 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.
- Firth NA. Marijuana use and oral cancer: a review. Oral Oncol 1997; 33:398.
- Zhang ZF, Morgenstern H, Spitz MR, et al. Marijuana use and increased risk of squamous cell carcinoma of the head and neck. Cancer Epidemiol Biomarkers Prev 1999; 8:1071.
- Aldington S, Harwood M, Cox B, et al. Cannabis use and cancer of the head and neck: case-control study. Otolaryngol Head Neck Surg 2008; 138:374.
- Hashibe M, Morgenstern H, Cui Y, et al. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiol Biomarkers Prev 2006; 15:1829.
- Kato I, Nomura AM. Alcohol in the aetiology of upper aerodigestive tract cancer. Eur J Cancer B Oral Oncol 1994; 30B:75.
- Hashibe M, Brennan P, Benhamou S, 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; 99:777.
- De Stefani E, Boffetta P, Oreggia F, et al. Hard liquor drinking is associated with higher risk of cancer of the oral cavity and pharynx than wine drinking. A case-control study in Uruguay. Oral Oncol 1998; 34:99.
- Murata M, Takayama K, Choi BC, Pak AW. A nested case-control study on alcohol drinking, tobacco smoking, and cancer. Cancer Detect Prev 1996; 20:557.
- Druesne-Pecollo N, Tehard B, Mallet Y, et al. Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer. Lancet Oncol 2009; 10:173.
- Cruz I, Van den Brule AJ, Steenbergen RD, et al. Prevalence of Epstein-Barr virus in oral squamous cell carcinomas, premalignant lesions and normal mucosa--a study using the polymerase chain reaction. Oral Oncol 1997; 33:182.
- Kobayashi I, Shima K, Saito I, et al. Prevalence of Epstein-Barr virus in oral squamous cell carcinoma. J Pathol 1999; 189:34.
- Cruz I, Van Den Brule AJ, Brink AA, et al. No direct role for Epstein-Barr virus in oral carcinogenesis: a study at the DNA, RNA and protein levels. Int J Cancer 2000; 86:356.
- Goldenberg D, Benoit NE, Begum S, et al. Epstein-Barr virus in head and neck cancer assessed by quantitative polymerase chain reaction. Laryngoscope 2004; 114:1027.
- Shillitoe EJ, Greenspan D, Greenspan JS, Silverman S Jr. Five-year survival of patients with oral cancer and its association with antibody to herpes simplex virus. Cancer 1986; 58:2256.
- Larsson PA, Edström S, Westin T, et al. Reactivity against herpes simplex virus in patients with head and neck cancer. Int J Cancer 1991; 49:14.
- Das CM, Schantz SP, Shillitoe EJ. Antibody to a mutagenic peptide of herpes simplex virus in young adult patients with cancer of the head and neck. Oral Surg Oral Med Oral Pathol 1993; 75:610.
- Mahale P, Sturgis EM, Tweardy DJ, et al. Association Between Hepatitis C Virus and Head and Neck Cancers. J Natl Cancer Inst 2016; 108.
- Rabinovics N, Mizrachi A, Hadar T, et al. Cancer of the head and neck region in solid organ transplant recipients. Head Neck 2014; 36:181.
- 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; 135:1433.
- Vaughan TL, Stewart PA, Davis S, Thomas DB. Work in dry cleaning and the incidence of cancer of the oral cavity, larynx, and oesophagus. Occup Environ Med 1997; 54:692.
- Becher H, Ramroth H, Ahrens W, et al. Occupation, exposure to polycyclic aromatic hydrocarbons and laryngeal cancer risk. Int J Cancer 2005; 116:451.
- Gordon I, Boffetta P, Demers PA. A case study comparing a meta-analysis and a pooled analysis of studies of sinonasal cancer among wood workers. Epidemiology 1998; 9:518.
- Dietz A, Ramroth H, Urban T, et al. Exposure to cement dust, related occupational groups and laryngeal cancer risk: results of a population based case-control study. Int J Cancer 2004; 108:907.
- Maier H, De Vries N, Snow GB. Occupational factors in the aetiology of head and neck cancer. Clin Otolaryngol Allied Sci 1991; 16:406.
- Vaughan TL, Strader C, Davis S, Daling JR. Formaldehyde and cancers of the pharynx, sinus and nasal cavity: I. Occupational exposures. Int J Cancer 1986; 38:677.
- Hauptmann M, Lubin JH, Stewart PA, et al. Mortality from solid cancers among workers in formaldehyde industries. Am J Epidemiol 2004; 159:1117.
- Vaughan TL, Stewart PA, Teschke K, et al. Occupational exposure to formaldehyde and wood dust and nasopharyngeal carcinoma. Occup Environ Med 2000; 57:376.
- Schneider AB, Lubin J, Ron E, et al. Salivary gland tumors after childhood radiation treatment for benign conditions of the head and neck: dose-response relationships. Radiat Res 1998; 149:625.
- Miyahara H, Sato T, Yoshino K. Radiation-induced cancers of the head and neck region. Acta Otolaryngol Suppl 1998; 533:60.
- van der Laan BF, Baris G, Gregor RT, et al. Radiation-induced tumours of the head and neck. J Laryngol Otol 1995; 109:346.
- Sale KA, Wallace DI, Girod DA, Tsue TT. Radiation-induced malignancy of the head and neck. Otolaryngol Head Neck Surg 2004; 131:643.
- Whatley WS, Thompson JW, Rao B. Salivary gland tumors in survivors of childhood cancer. Otolaryngol Head Neck Surg 2006; 134:385.
- Kang HK. Feasibility of an epidemiologic study of submariners who received radium irradiation treatment. Otolaryngol Head Neck Surg 1996; 115:433.
- Freedman ND, Park Y, Subar AF, et al. Fruit and vegetable intake and head and neck cancer risk in a large United States prospective cohort study. Int J Cancer 2008; 122:2330.
- Boeing H, Dietrich T, Hoffmann K, et al. Intake of fruits and vegetables and risk of cancer of the upper aero-digestive tract: the prospective EPIC-study. Cancer Causes Control 2006; 17:957.
- Farrow DC, Vaughan TL, Berwick M, et al. Diet and nasopharyngeal cancer in a low-risk population. Int J Cancer 1998; 78:675.
- Lacko M, Braakhuis BJ, Sturgis EM, et al. Genetic susceptibility to head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2014; 89:38.
- Kutler DI, Singh B, Satagopan J, et al. A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood 2003; 101:1249.
- Rosenberg PS, Alter BP, Ebell W. Cancer risks in Fanconi anemia: findings from the German Fanconi Anemia Registry. Haematologica 2008; 93:511.
- Birkeland AC, Auerbach AD, Sanborn E, et al. Postoperative clinical radiosensitivity in patients with fanconi anemia and head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2011; 137:930.
- Velly AM, Franco EL, Schlecht N, et al. Relationship between dental factors and risk of upper aerodigestive tract cancer. Oral Oncol 1998; 34:284.
- Tezal M, Sullivan MA, Reid ME, et al. Chronic periodontitis and the risk of tongue cancer. Arch Otolaryngol Head Neck Surg 2007; 133:450.
- Campbell BH, Mark DH, Soneson EA, et al. The role of dental prostheses in alveolar ridge squamous carcinomas. Arch Otolaryngol Head Neck Surg 1997; 123:1112.
- Morse DE, Katz RV, Pendrys DG, et al. Mouthwash use and dentures in relation to oral epithelial dysplasia. Oral Oncol 1997; 33:338.
- Lockhart PB, Norris CM Jr, Pulliam C. Dental factors in the genesis of squamous cell carcinoma of the oral cavity. Oral Oncol 1998; 34:133.
- Schildt EB, Eriksson M, Hardell L, Magnuson A. Oral infections and dental factors in relation to oral cancer: a Swedish case--control study. Eur J Cancer Prev 1998; 7:201.
- Gandini S, Negri E, Boffetta P, et al. Mouthwash and oral cancer risk quantitative meta-analysis of epidemiologic studies. Ann Agric Environ Med 2012; 19:173.
- Guha N, Boffetta P, Wünsch Filho V, 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; 166:1159.