The significance of p16 protein expression in oral squamous cell carcinoma
Authors:
S. Maléřová 1; D. Kalfeřt 1; M. Grega 2; R. Tachezy 3
; J. Klozar 1
Authors place of work:
Klinika otorinolaryngologie a chirurgie hlavy a krku, 2. lékařská fakulta, Univerzita Karlova v Praze, Fakultní nemocnice v Motole, Praha
1; Ústav patologie a molekulární medicíny 2. lékařská fakulta, Univerzita Karlova v Praze, Fakultní nemocnice v Motole, Praha
2; Katedra genetiky a mikrobiologie, Přírodovědecká fakulta Univerzity Karlovy, BIOCEV, Praha
3
Published in the journal:
Epidemiol. Mikrobiol. Imunol. 69, 2020, č. 2, s. 64-72
Category:
Original Papers
Summary
Introduction: Human papillomavirus (HPV) infection plays an important role in the etiopathogenesis of oropharyngeal squamous cell carcinomas. HPV detection in these tumours is a positive prognostic marker. The p16 protein expression, which is detected immunohistochemically, is an indirect marker of active HPV infection. Unlike in oropharyngeal carcinoma, in oral carcinoma, the prognostic significance of HPV/p16 positivity is unclear. Some studies even show a worse prognosis in patients with HPV/p16 positive oral carcinoma. The aim of our study is to consider the significance of p16 protein expression in relation to clinicopathological parameters and prognosis in patients with oral squamous cell carcinomas.
Methods: One hundred and twenty patients treated surgically for oral carcinoma were enrolled in the study. The most common anatomical sites of oral carcinoma were the tongue body (54; 45% of cases) and floor of mouth (35; 29.2% of cases). All tumours were analysed immunohistochemically for p16 protein expression. The results were correlated with the clinicopathological parameters and analysed statistically.
Results: Ten patients (8.3%) tested positive for p16 expression. In the study cohort, p16 expression was identified as the most significant factor with a negative effect on survival (p=0.019). Based on the Cox proportional hazard model, the p16-positive patients had four times worse survival than the p16-negative ones. Other factors with a statistically significant effect on survival were T status, N status, and recurrence.
Conclusion: The significance of p16 expression differs between oral and oropharyngeal carcinomas. The p16 positivity seems to be a negative prognostic factor in oral carcinomas. Nevertheless, the significance of HPV presence in tumours outside the oropharyngeal area remains unclear.
Keywords:
Prognosis – p16 expression – oral carcinoma
Zdroje
1. Abrahao R, Anantharaman D, Gaborieau V, et al. The influence of smoking, age and stage at diagnosis on the survival after larynx, hypopharynx and oral cavity cancers in Europe: The ARCAGE study. Int J Cancer, 2018;143(1):32–44.
2. Blahak J, Zelinka J, Gumulec J, et al. HPV, protein p16 and squamous cell carcinoma of the oral cavity. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2019. [Ahead of Print].
3. Blot WJ, McLaughlin JK, Winn DM, et al. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res, 1988;48(11):3282–3287.
4. De Morais EF, Mafra RP, Gonzaga AKG, et al. Prognostic factors of oral squamous cell carcinoma in young patients: A systematic review. J Oral Maxillofac Surg, 2017;75(7):1555–1566.
5. Dediol E, Sabol I, Virag M, et al. HPV prevalence and p16INKa overexpression in non-smoking non-drinking oral cavity cancer patients. Oral Dis, 2016;22(6):517–522.
6. Duray A, Descamps G, Decaestecker C, et al. Human papillomavirus DNA strongly correlates with a poorer prognosis in oral cavity carcinoma. Laryngoscope, 2012;122(7):1558–1565.
7. Gotz C, Drecoll E, Straub M, et al. Impact of HPV infection on oral squamous cell carcinoma. Oncotarget, 2016;7(47):76704–76712.
8. Grobe A, Hanken H, Kluwe L, et al. Immunohistochemical analysis of p16 expression, HPV infection and its prognostic utility in oral squamous cell carcinoma. J Oral Pathol Med, 2013;42(9):676–681.
9. Hoffmann M, Tribius S, Quabius ES, et al. HPV DNA, E6*I-mRNA expression and p16INK4A immunohistochemistry in head and neck cancer – how valid is p16INK4A as surrogate marker? Cancer Lett, 2012;323(1):88–96.
10. Kalfert D, Ludvikova M, Topolcan O, et al. Analysis of preoperative serum levels of MMP1, -2, and -9 in patients with site-specific head and neck squamous cell cancer. Anticancer Res, 2014;34(12):7431–7441.
11. Klozar J. Clinical relevance of human papillomavirus outside of oropharynx. Curr Opin Otolaryngol Head Neck Surg, 2019;27(2):80–84.
12. Koslabova E, Hamsikova E, Salakova M, et al. Markers of HPV infection and survival in patients with head and neck tumors. Int J Cancer, 2013;133(8):1832–1839.
13. Lee LA, Huang CG, Tsao KC, et al. Human Papillomavirus Infections are Common and Predict Mortality in a Retrospective Cohort Study of Taiwanese Patients With Oral Cavity Cancer. Medicine (Baltimore), 2015;94(47):e2069.
14. Lewis JS Jr, Beadle B, Bishop JA, et al. Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists. Arch Pathol Lab Med., 2018;142(5):559–597.
15. Lydiatt WM, Patel SG, O‘Sullivan B, et al. Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin, 2017;67(2):122–137.
16. Meshman J, Wang PC, Chin R, et al. Prognostic significance of p16 in squamous cell carcinoma of the larynx and hypopharynx. Am J Otolaryngol, 2017;38(1):31–37.
17. Minami K, Kogashiwa Y, Ebihara Y, et al. Human papillomavirus and p16 protein expression as prognostic biomarkers in mobile tongue cancer. Acta Otolaryngol, 2017;137(10):1121–1126.
18. Nemes JA, Deli L, Nemes Z, et al. Expression of p16(INK4A), p53, and Rb proteins are independent from the presence of human papillomavirus genes in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2006;102(3):344–352.
19. Novák Š, Bandurová V, Mifková A, et al. Nádorové mikroprostredi. Otorinolaryng a Foniat., 2019;68(1):41–51.
20. O‘Sullivan B, Huang SH, Su J, et al. Development and valida-tion of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol, 2016;17(4):440–451.
21. Omura-Minamisawa M, Diccianni MB, Chang RC, et al. p16/p14(ARF) cell cycle regulatory pathways in primary neuroblastoma: p16 expres-sion is associated with advanced stage disease. Clin Cancer Res, 2001;7(11):3481–3490.
22. Rodriguez-Santamarta T, Rodrigo JP, Garcia-Pedrero JM, et al. Prevalence of human papillomavirus in oral squamous cell carcinomas in northern Spain. Eur Arch Otorhinolaryngol, 2016;273(12):4549–4559.
23. Rotnaglova E, Tachezy R, Salakova M, et al. HPV involvement in tonsillar cancer: prognostic significance and clinically relevant markers. Int J Cancer, 2011;129(1):101–110.
24. Saghravanian N, Zamanzadeh M, Meshkat Z, et al. Evaluation of the Prevalence Rate and the Prognostic Effect of Human Papilloma Virus Infection in a Group of Patients With Oral Cavity Squamous Cell Carcinoma. Iran J Cancer Prev, 2016;9(3):e3998.
25. Satgunaseelan L, Virk SA, Lum T, et al. p16 expression independent of human papillomavirus is associated with lower stage and longer disease-free survival in oral cavity squamous cell carcinoma. Pathology, 2016;48(5):441–448.
26. Simonidesova S, Hamsikova E, Klozar J, et al. Výskyt orální HPV infekce u zdravé populace – systematický přehled se zaměřením na evropskou populaci. Epidemiol. Mikrobiol. Imunol, 2018;67(4):175–183.
27. Tachezy R, Smahelova J, Kaspirkova J, et al. Human papillomavirus type-specific prevalence in the cervical cancer screening population of Czech women. PLoS One, 2013;8:e79156.
28. Yanagawa N, Tamura G, Oizumi H, et al. Frequent epigenetic silencing of the p16 gene in non-small cell lung cancers of tobacco smokers. Jpn J Cancer Res, 2002;93(10):1107–1113.
Štítky
Hygiene and epidemiology Medical virology Clinical microbiologyČlánok vyšiel v časopise
Epidemiology, Microbiology, Immunology
2020 Číslo 2
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