Cancer Epidemiology Biomarkers & Prevention, Vol 5, Issue 7 567-575, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Human papillomavirus and cancers of the upper aerodigestive tract: a review of epidemiological and experimental evidence

S Franceschi, N Munoz, XF Bosch, PJ Snijders and JM Walboomers
Servizio di Epidemiologia, Centro di Riferimento Oncologico, Aviano PN, Italy.

Human papillomaviruses (HPVs) are recognized as important causes of cancer of the anogenital tract and may be involved also in the etiology of cancers of the upper aerodigestive tract (UADT). Epidemiological and experimental evidence lend some support to this possibility. Increased risk of cancer of the oral cavity, pharynx, and larynx subsequent to the occurrence of cancer of the cervix has been found and suggests common etiological factors besides smoking. HPV has been found in a substantial proportion of benign UADT lesions, most notably laryngeal papillomas and oral verrucal-papillary lesions. Largest and most accurate case series (i.e., > 15 UADT cancer cases, based on best HPV detection techniques) showed HPV DNA in 46% of cancers of the oral cavity and pharynx, 15% of cancers of the esophagus, and 24% of cancers of the larynx, with however, great discrepancies from one study to another. An additional 14 case series with a comparison group of noncancer patients revealed approximately a 4-fold higher HPV prevalence in UADT cancer tissues than in normal ones. The only two strictly designed case-control studies dealt with cancer of the oral cavity and provided inconclusive results, possibly because of interference of primary treatment with HPV detection in buccal exfoliated cells. An increasing bulk of experimental and in vitro evidence suggests that at least a proportion of UADT cancers harbor a relatively high copy number of HPV DNA. E6/E7 region transcripts and a clonal association with HPV have been demonstrated in these tumors. The combination of a good study design with reliable and noninvasive viral measurement will ultimately allow researchers to elucidate the role of HPV in the development of UADT cancer. Allowance for the strong effect of smoking, alcohol drinking, and betel quid chewing on UADT cancer and exclusion of noncausal associations will be the most difficult challenges of such studies.

This article has been cited by other articles:

				D. Ting Hsiung, C. J. Marsit, E. A. Houseman, K. Eddy, C. S. Furniss, M. D. McClean, and K. T. Kelsey Global DNA Methylation Level in Whole Blood as a Biomarker in Head and Neck Squamous Cell Carcinoma Cancer Epidemiol. Biomarkers Prev., January 1, 2007; 16(1): 108 - 114. [Abstract] [Full Text] [PDF]

				P. M. Weinberger, Z. Yu, B. G. Haffty, D. Kowalski, M. Harigopal, J. Brandsma, C. Sasaki, J. Joe, R. L. Camp, D. L. Rimm, et al. Molecular Classification Identifies a Subset of Human Papillomavirus-Associated Oropharyngeal Cancers With Favorable Prognosis J. Clin. Oncol., February 10, 2006; 24(5): 736 - 747. [Abstract] [Full Text] [PDF]

				A. R. Kreimer, G. M. Clifford, P. Boyle, and S. Franceschi Human Papillomavirus Types in Head and Neck Squamous Cell Carcinomas Worldwide: A Systematic Review Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 467 - 475. [Abstract] [Full Text] [PDF]

				A. S. Tsao, E. S. Kim, and W. K. Hong Chemoprevention of Cancer CA Cancer J Clin, May 1, 2004; 54(3): 150 - 180. [Abstract] [Full Text] [PDF]

				S Syrjanen HPV infections and tonsillar carcinoma J. Clin. Pathol., May 1, 2004; 57(5): 449 - 455. [Abstract] [Full Text] [PDF]

				M. Dai, G. M. Clifford, F. le Calvez, X. Castellsague, P. J. F. Snijders, M. Pawlita, R. Herrero, P. Hainaut, and S. Franceschi Human Papillomavirus Type 16 and TP53 Mutation in Oral Cancer: Matched Analysis of the IARC Multicenter Study Cancer Res., January 15, 2004; 64(2): 468 - 471. [Abstract] [Full Text] [PDF]

				R. Herrero, X. Castellsague, M. Pawlita, J. Lissowska, F. Kee, P. Balaram, T. Rajkumar, H. Sridhar, B. Rose, J. Pintos, et al. Human Papillomavirus and Oral Cancer: The International Agency for Research on Cancer Multicenter Study J Natl Cancer Inst, December 3, 2003; 95(23): 1772 - 1783. [Abstract] [Full Text] [PDF]

				K. Devaraj, M. L. Gillison, and T.-C. Wu DEVELOPMENT OF HPV VACCINES FOR HPV-ASSOCIATED HEAD AND NECK SQUAMOUS CELL CARCINOMA Crit. Rev. Oral. Biol. Med., September 1, 2003; 14(5): 345 - 362. [Abstract] [Full Text] [PDF]

				S. M. Dong, D.-I. Sun, N. E. Benoit, I. Kuzmin, M. I. Lerman, and D. Sidransky Epigenetic Inactivation of RASSF1A in Head and Neck Cancer Clin. Cancer Res., September 1, 2003; 9(10): 3635 - 3640. [Abstract] [Full Text] [PDF]

				R. Herrero Chapter 7: Human Papillomavirus and Cancer of the Upper Aerodigestive Tract J Natl Cancer Inst Monographs, June 1, 2003; 2003(31): 47 - 51. [Abstract] [Full Text] [PDF]

				K J Syrjanen HPV infections and oesophageal cancer J. Clin. Pathol., October 1, 2002; 55(10): 721 - 728. [Abstract] [Full Text] [PDF]

				E. Ringstrom, E. Peters, M. Hasegawa, M. Posner, M. Liu, and K. T. Kelsey Human Papillomavirus Type 16 and Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., October 1, 2002; 8(10): 3187 - 3192. [Abstract] [Full Text] [PDF]

				P. K. Ha, S. I. Pai, W. H. Westra, M. L. Gillison, B. C. Tong, D. Sidransky, and J. A. Califano Real-Time Quantitative PCR Demonstrates Low Prevalence of Human Papillomavirus Type 16 in Premalignant and Malignant Lesions of the Oral Cavity Clin. Cancer Res., May 1, 2002; 8(5): 1203 - 1209. [Abstract] [Full Text] [PDF]

				L. Morris Brown, R. Hoover, D. Silverman, D. Baris, R. Hayes, G. M. Swanson, J. Schoenberg, R. Greenberg, J. Liff, A. Schwartz, et al. Excess Incidence of Squamous Cell Esophageal Cancer among US Black Men: Role of Social Class and Other Risk Factors Am. J. Epidemiol., January 15, 2001; 153(2): 114 - 122. [Abstract] [Full Text] [PDF]

				D. T. W. Wong and K. Munger Association of Human Papillomaviruses With a Subgroup of Head and Neck Squamous Cell Carcinomas J Natl Cancer Inst, May 3, 2000; 92(9): 675 - 677. [Full Text] [PDF]

				M. L. Gillison, W. M. Koch, R. B. Capone, M. Spafford, W. H. Westra, L. Wu, M. L. Zahurak, R. W. Daniel, M. Viglione, D. E. Symer, et al. Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers J Natl Cancer Inst, May 3, 2000; 92(9): 709 - 720. [Abstract] [Full Text] [PDF]