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Review
. 2010 Aug;11(8):781-9.
doi: 10.1016/S1470-2045(10)70017-6. Epub 2010 May 5.

HPV-associated head and neck cancer: a virus-related cancer epidemic

Shanthi Marur  1 , Gypsyamber D'Souza, William H Westra, Arlene A Forastiere
Affiliations
Review

HPV-associated head and neck cancer: a virus-related cancer epidemic

Shanthi Marur et al. Lancet Oncol. 2010 Aug.

Abstract

A rise in incidence of oropharyngeal squamous cell cancer--specifically of the lingual and palatine tonsils--in white men younger than age 50 years who have no history of alcohol or tobacco use has been recorded over the past decade. This malignant disease is associated with human papillomavirus (HPV) 16 infection. The biology of HPV-positive oropharyngeal cancer is distinct with P53 degradation, retinoblastoma RB pathway inactivation, and P16 upregulation. By contrast, tobacco-related oropharyngeal cancer is characterised by TP53 mutation and downregulation of CDKN2A (encoding P16). The best method to detect virus in tumour is controversial, and both in-situ hybridisation and PCR are commonly used; P16 immunohistochemistry could serve as a potential surrogate marker. HPV-positive oropharyngeal cancer seems to be more responsive to chemotherapy and radiation than HPV-negative disease. HPV 16 is a prognostic marker for enhanced overall and disease-free survival, but its use as a predictive marker has not yet been proven. Many questions about the natural history of oral HPV infection remain under investigation. For example, why does the increase in HPV-related oropharyngeal cancer dominate in men? What is the potential of HPV vaccines for primary prevention? Could an accurate method to detect HPV in tumour be developed? Which treatment strategies reduce toxic effects without compromising survival? Our aim with this review is to highlight current understanding of the epidemiology, biology, detection, and management of HPV-related oropharyngeal head and neck squamous cell carcinoma, and to describe unresolved issues.

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Conflict of interest statement

The authors declared not conflicts of interest.

Figures

Figure One
Figure One
Human Papilloma Virus-16 is the oncogenic form of all HPV types that is frequently associated with oropharyngeal HNSCC. This figure illustrates the genetic composition of HPV-16 DNA virus. E6 and E7 oncoproteins, dysregulation plays a key role in distinct biology of HPV associated oropharyngeal HNSCC. Image obtained from www.dnachip-link.com/Eng/library/HPV.asp. Biomedlab Co.
Figure Two
Figure Two
Proportion of oropharyngeal (panel A) and head and neck (panel B) squamous cell carcinoma (HNSCC) that are caused by HPV in North America and Europe. Only studies with more than 25 oropharynx (panel A: 27 studies), – or 50 HNSCC (panel B: 30 studies)–, , – cases were included.
Figure Three
Figure Three
Age-adjusted incidence rates of HPV-related (panels A & C) and HPV-unrelated (panels B & D) head and neck squamous cell cancer between 1973 and 2006, stratified by age at diagnosis. The annual percent change in incidence for each age category is shown next to each line; * indicates slope with p<0.05. As per Chaturvedi et al, HPV-related sites includes base of tongue, lingual tonsil, tonsil, oropharynx, and Waldeyer ring and HPV-unrelated sites includes other and unspecified parts of tongue, gum, floor of mouth, palate, and other parts of mouth. Graph generated with the assistance of Anil Chaturvedi, modified from similar graph in Chaturvedi et al. 2008 article.
Figure Four
Figure Four
Strips of metastatic non-keratinized squamous cell carcinoma aspirated from a cystic neck mass (A, hematoxylin and eosin). The presence of HPV is visualized as strong cytoplasmic and nuclear staining for p16 by immunohistochemistry (B), and as dot-like hybridization signals within the nuclei of tumor cells by HPV-16 in-situ hybridization (C).
See this image and copyright information in PMC

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