Human papillomavirus, p16 and p53 expression associated with survival of head and neck cancer
- PMID: 20181227
- PMCID: PMC2841067
- DOI: 10.1186/1750-9378-5-4
Human papillomavirus, p16 and p53 expression associated with survival of head and neck cancer
Abstract
Background: P16 and p53 protein expression, and high-risk human papillomavirus (HPV-HR) types have been associated with survival in head and neck cancer (HNC). Evidence suggests that multiple molecular pathways need to be targeted to improve the poor prognosis of HNC. This study examined the individual and joint effects of tumor markers for differences in predicting HNC survival. P16 and p53 expression were detected from formalin-fixed, paraffin-embedded tissues by immunohistochemical staining. HPV DNA was detected by PCR and DNA sequencing in 237 histologically confirmed HNC patients.
Results: Overexpression of p16 (p16+) and p53 (p53+) occurred in 38% and 48% of HNC tumors, respectively. HPV-HR was detected in 28% of tumors. Worse prognosis was found in tumors that were p53+ (disease-specific mortality: adjusted hazard ratios, HR = 1.9, 95% CI: 1.04-3.4) or HPV- (overall survival: adj. HR = 2.1, 1.1-4.3) but no association in survival was found by p16 status. Compared to the molecular marker group with the best prognosis (p16+/p53-/HPV-HR: referent), the p16-/p53+/HPV- group had the lowest overall survival (84% vs. 60%, p < 0.01; HR = 4.1, 1.7-9.9) and disease-specific survival (86% vs. 66%, p < 0.01; HR = 4.0, 1.5-10.7). Compared to the referent, the HRs of the other six joint biomarker groups ranged from 1.6-3.4 for overall mortality and 0.9-3.9 for disease-specific mortality.
Conclusion: The p16/p53/HPV joint groups showed greater distinction in clinical outcomes compared to results based on the individual biomarkers alone. This finding suggests that assessing multiple molecular markers in HNC patients will better predict the diverse outcomes and potentially the type of treatment targeted to those markers.
Figures



Similar articles
-
P16INK4a expression, human papillomavirus, and survival in head and neck cancer.Oral Oncol. 2008 Feb;44(2):133-42. doi: 10.1016/j.oraloncology.2007.01.010. Epub 2007 Mar 13. Oral Oncol. 2008. PMID: 17360226
-
Association between p53 and human papillomavirus in head and neck cancer survival.Cancer Epidemiol Biomarkers Prev. 2008 Feb;17(2):421-7. doi: 10.1158/1055-9965.EPI-07-2597. Cancer Epidemiol Biomarkers Prev. 2008. PMID: 18268127
-
Prognostic significance of cell cycle-associated proteins p16, pRB, cyclin D1 and p53 in resected oropharyngeal carcinoma.J Otolaryngol Head Neck Surg. 2018 Sep 6;47(1):53. doi: 10.1186/s40463-018-0298-3. J Otolaryngol Head Neck Surg. 2018. PMID: 30189895 Free PMC article.
-
A Systematic Review and Meta-Analysis of Prognostic Biomarkers in Anal Squamous Cell Carcinoma Treated With Primary Chemoradiotherapy.Clin Oncol (R Coll Radiol). 2019 Dec;31(12):e1-e13. doi: 10.1016/j.clon.2019.06.013. Epub 2019 Jul 10. Clin Oncol (R Coll Radiol). 2019. PMID: 31301958
-
The prognostic value of p16 and p53 expression for survival after vulvar cancer: A systematic review and meta-analysis.Gynecol Oncol. 2019 Jan;152(1):208-217. doi: 10.1016/j.ygyno.2018.10.015. Epub 2018 Nov 8. Gynecol Oncol. 2019. PMID: 30415992
Cited by
-
A Decade of Global mRNA and miRNA Profiling of HPV-Positive Cell Lines and Clinical Specimens.Open Virol J. 2012;6:216-31. doi: 10.2174/1874357901206010216. Epub 2012 Dec 28. Open Virol J. 2012. PMID: 23341857 Free PMC article.
-
Combined Effect of HPV and Several Gene SNPs in Laryngeal Cancer.Medicina (Kaunas). 2020 Feb 17;56(2):81. doi: 10.3390/medicina56020081. Medicina (Kaunas). 2020. PMID: 32079256 Free PMC article.
-
Overexpression of prothymosin alpha predicts poor disease outcome in head and neck cancer.PLoS One. 2011 May 5;6(5):e19213. doi: 10.1371/journal.pone.0019213. PLoS One. 2011. PMID: 21573209 Free PMC article.
-
Human papillomavirus genotype and oropharynx cancer survival in the United States of America.Eur J Cancer. 2015 Dec;51(18):2759-67. doi: 10.1016/j.ejca.2015.09.005. Epub 2015 Nov 18. Eur J Cancer. 2015. PMID: 26602016 Free PMC article.
-
Genetic alterations of RD(INK4/ARF) enhancer in human cancer cells.Mol Carcinog. 2014 Mar;53(3):211-8. doi: 10.1002/mc.21965. Epub 2012 Oct 12. Mol Carcinog. 2014. PMID: 23065809 Free PMC article.
References
-
- Ries L, Eisner M, Kosary C, Hankey BF, Miller BA, Clegg L, Mariotto A, Feuer EJ, Edwards BK, (eds) SEER Cancer Statistics Review, 1975-2001. Bethesda, MD: National Cancer Institute; 2004.
-
- Haraf DJ, Nodzenski E, Brachman D, Mick R, Montag A, Graves D, Vokes EE, Weichselbaum RR. Human papilloma virus and p53 in head and neck cancer: clinical correlates and survival. Clin Cancer Res. 1996;2:755–62. - PubMed
-
- Smith EM, Ritchie JM, Summersgill KF, Hoffman HT, Wang DH, Haugen TH, Turek LP. Human papillomavirus in oral exfoliated cells and risk of head and neck cancer. J Natl Cancer Inst. 2004;96:449–55. - PubMed
-
- Andl T, Kahn T, Pfuhl A, Nicola T, Erber R, Conradt C, Klein W, Helbig M, Dietz A, Weidauer H, Bosch FX. Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control. Cancer Res. 1998;58:5–13. - PubMed
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous