Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck.

Abstract

PURPOSE:

A subset of head and neck cancers is associated with the human papillomavirus (HPV). Viral infection is closely correlated with expression of p16(INK4A) in these tumors. We evaluated p16(INK4A) as a prognostic marker of treatment response and survival in a well-defined and prospectively collected cohort of patients treated solely with conventional radiotherapy in the Danish Head and Neck Cancer Group (DAHANCA) 5 trial.

PATIENTS AND METHODS:

Immunohistochemical expression of p16(INK4A) was analyzed in pretreatment paraffin-embedded tumor blocks from 156 patients treated with conventional primary radiotherapy alone. The influence of p16(INK4A) status on locoregional tumor control, disease-specific survival, and overall survival after radiotherapy was evaluated.

RESULTS:

p16(INK4A) positivity was found in 35 tumors (22%). Tumor-positivity for p16(INK4A) was significantly correlated with improved locoregional tumor control (5-year actuarial values 58% v 28%; P = .0005), improved disease-specific survival (72% v 34%; P = .0006), and improved overall survival (62% v 26%; P = .0003). In multivariate analysis, p16(INK4A) remained a strong independent prognostic factor for locoregional failure (hazard ratio [HR], 0.35; 95% CI, 0.19 to 0.64), disease-specific death (HR, 0.36; 95% CI, 0.20 to 0.64), and overall death (HR, 0.44; 95% CI, 0.28 to 0.68).

CONCLUSION:

Expression of p16(INK4A) has a major impact on treatment response and survival in patients with head and neck cancer treated with conventional radiotherapy.

• Authors: Pernille Lassen, Jesper G Eriksen, Stephen Hamilton-Dutoit, Trine Tramm, Jan Alsner, Jens Overgaard
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 12 Pg. 1992-8 (Apr 20 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19289615 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Cyclin-Dependent Kinase Inhibitor p16
• Placebos

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Carcinoma, Squamous Cell (metabolism, mortality, radiotherapy, virology)
• Cohort Studies
• Cyclin-Dependent Kinase Inhibitor p16 (metabolism)
• Female
• Follow-Up Studies
• Head and Neck Neoplasms (metabolism, mortality, radiotherapy, virology)
• Humans
• In Situ Hybridization
• Male
• Middle Aged
• Neoplasm Staging
• Papillomaviridae (isolation & purification)
• Papillomavirus Infections (metabolism, mortality, radiotherapy, virology)
• Placebos
• Prognosis
• Prospective Studies
• Survival Rate
• Treatment Outcome
• Young Adult