Summary and Further Reading

Chapter 1 - Epidemiology, Risk Factors and Pathogenesis of Squamous Cell Tumours


  • HNSCC encompasses a heterogeneous group of upper aerodigestive malignancies originating in the lip, oral cavity, pharynx and larynx
  • It is the sixth most common cancer worldwide, accounting for 1%–2% of all cancer-related deaths
  • Historically, HNSCC has been associated with tobacco smoking and alcohol use
  • Globally, the incidence of tobacco-related HNSCC is associated with patterns of tobacco use and is decreasing in countries with declining rates of tobacco consumption
  • In the past decade, infection with high-risk HPV and especially with HPV16 has been implicated in the pathogenesis of a growing subset of HNSCCs, mainly those arising from the oropharynx
  • HPV-related OPC represents a distinct entity in terms of biology and clinical behaviour
  • Five-year survival rates for all stages of HNSCC is approximately 65%. High cure rates are reported with localised and locoregional disease, but prognosis is dismal for recurrent or metastatic disease
  • For HNSCC, malignant transformation of normal mucosa to invasive carcinoma follows a molecular progression model of multistep carcinogenesis
  • Tobacco-related HNSCC demonstrates mutation of the p53 gene and downregulation of the p16 protein
  • On the contrary, HPV-associated OPC is typically characterised by wild-type p53 and RB genes and upregulation of p53 protein levels

Further Reading

Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 2008; 26:612–619.

Gatta G, Botta L, Sánchez 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; 51:2130–2143. 

Hashibe M, Brennan P, Chuang SC, et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 2009; 18:541–550.

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60:277–300.

Klein JD, Grandis JR. The molecular pathogenesis of head and neck cancer. Cancer Biol Ther 2010; 9:1–7.

Marur S, D’Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 2010; 11:781–789.

Park BJ, Chiosea SI, Grandis JR. Molecular changes in the multistage pathogenesis of head and neck cancer. Cancer Biomark 2010; 9:325–339.

Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol 2014; 25:2101–2115.

Psyrri A, Seiwert TY, Jimeno A. Molecular pathways in head and neck cancer: EGFR, PI3K, and more. Am Soc Clin Oncol Educ Book 2013:246–255. 

Rampias T, Sasaki C, Psyrri A. Molecular mechanisms of HPV induced carcinogenesis in head and neck. Oral Oncol 2014; 50:356–363. 

Rettig EM, D’Souza G. Epidemiology of head and neck cancer. Surg Oncol Clin N Am 2015; 24:379–396.

Last update: 26 July 2017