Inverse Relationship between Human Papillomavirus-16 Infection and Disruptivep53Gene Mutations in Squamous Cell Carcinoma of the Head and Neck
Top Cited Papers
- 15 January 2008
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 14 (2), 366-369
- https://doi.org/10.1158/1078-0432.ccr-07-1402
Abstract
Purpose: Squamous cell carcinomas of the head and neck (HNSCC) often harbor p53 mutations, but p53 protein degradation by the viral oncoprotein E6 may supercede p53 mutations in human papillomavirus 16 (HPV16)–positive tumors. The prevalence of p53 mutations in HPV-positive HNSCCs is indeed lower, but in some tumors these alterations coexist. The purpose of this study was to discern whether HNSCCs differ in the type of p53 mutations as a function of HPV16 status. Experimental Design: The study was nested within a prospective multicenter study (ECOGE 4393/RTOG R9614) of patients with HNSCC treated surgically with curative intent. Tumors from one study center were used to construct a tissue microarray. The tumors were well characterized with respect to p53 mutational status. The tissue microarray was evaluated by HPV16 in situ hybridization. HPV16 analysis was also done on a select group of tonsillar carcinomas known to harbor disruptive p53 mutations defined as stop mutations or nonconservative mutations within the DNA binding domain. Results: HPV16 was detected in 12 of 89 (13%) HNSCCs. By tumor site, HPV16 was detected in 12 of 21 (57%) tumors from the palatine/lingual tonsils, but in none of 68 tumors from nontonsillar sites (P < 0.00001). Both HPV16-positive and HPV16-negative HNSCCs harbored p53 mutations (25% versus 52%), but disruptive mutations were only encountered in HPV16-negative carcinomas. Of seven tonsillar carcinomas with disruptive p53 mutations, none were HPV16 positive, in contrast to HPV16-positive tonsillar carcinomas without disruptive p53 mutations (0% versus 57%; P = 0.008). Conclusions: Although HPV16 and mutated p53 may coexist in a subset of HNSCCs, HPV16 and disruptive p53 mutations seem to be nonoverlapping events. A less calamitous genetic profile, including the absence of disruptive p53 mutations, may underlie the emerging clinical profile of HPV16-positive HNSCC such as improved patient outcome.Keywords
This publication has 28 references indexed in Scilit:
- TP53Mutations and Survival in Squamous-Cell Carcinoma of the Head and NeckNew England Journal of Medicine, 2007
- High-Risk Human Papillomavirus Affects Prognosis in Patients With Surgically Treated Oropharyngeal Squamous Cell CarcinomaJournal of Clinical Oncology, 2006
- Human papillomavirus and p53 mutational status as prognostic factors in head and neck carcinomaHead & Neck, 2002
- Human papillomavirus positive squamous cell carcinoma of the oropharynxCancer, 2001
- Human Papillomavirus Infection as a Risk Factor for Squamous-Cell Carcinoma of the Head and NeckNew England Journal of Medicine, 2001
- Induction of the p53-target gene GADD45 in HPV-positive cancer cellsOncogene, 1999
- `Gain of function' phenotype of tumor-derived mutant p53 requires the oligomerization/nonsequence-specific nucleic acid-binding domainOncogene, 1998
- TP53 DNA contact mutations are selectively associated with allelic loss and have a strong clinical impact in head and neck cancerOncogene, 1998
- Analysis of p53 status in tonsillar carcinomas associated with human papillomavirusJournal of General Virology, 1994
- Crystal Structure of a p53 Tumor Suppressor-DNA Complex: Understanding Tumorigenic MutationsScience, 1994