Reliability evaluation of predictors in human papilloma virus-associated oropharyngeal squamous cell carcinoma
Keywords:
oropharyngeal squamous cell carcinoma, human papillomavirus status, PD-L1, p53, immunohistochemistry, predictor, correlationAbstract
Introduction. The progressive epidemic of the human papillomavirus (HPV) has led to an increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC). Positive HPV status is not always a reliable predictor of risk stratification in patients with OPSCC. Therefore, in order to improve the quality of the repertoire of prognostic predictors, it is necessary to identify additional indicators canonically related to the pathogenesis of HPV+OPSCC.
Methods. The study included 62 patients treated with OPSCC T1-4N0-3M0 (7th edition, AJCC) in 2015-2020 at the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology and in the Tashkent and Samarkand city branches. An immunohistochemical analysis was performed for p16INK4a, PD-L1, and p53 proteins. In the study, the correlation between predictors and HPV status was assessed by the Pearson coefficient, and their predictive potential was determined by the method of logistic regression.
Results. The most suitable predictors for establishing a positive HPV status in OPSCC are considered to be a relatively young age (up to 60 years) of patients, localization of the tumor in the palatine tonsils, negative expression of p53mutant, positive expression of p53wild regardless of intensity, low and medium levels (L and M) of PD-L1 expression, primary tumors on T1 and T2, early tumor stages according to the 8th edition of the TNM classification. Clinical demographic and molecular prognostic models based on these parameters have excellent predictive potential (AUC>0.9) and can be a reliable tool in the diagnosis of HPV+OPSCC (p<0.001).
Conclusion. Modern oncology certainly contributes to the effective assessment of toxicity, while facilitating the continuous evaluation of the effectiveness of ongoing therapy, which leads to more logical design of clinical trials than standard approaches. Therefore, it is very important to understand the impact of predictors with excellent predictive power on HPV+ patients when planning treatment and testing deintensification strategies.
References
Nichols AC, Theurer J, Prisman E, et al. Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial. J Clin Oncol. 2022;40(8):866-875. https://doi.org/10.1200/JCO.21.01961
Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. https://doi.org/10.1056/NEJMoa0912217
Chera BS, Amdur RJ. Current Status and Future Directions of Treatment Deintensification in Human Papilloma Virus-associated Oropharyngeal Squamous Cell Carcinoma. Semin Radiat Oncol. 2018;28(1):27-34. https://doi.org/10.1016/j.semradonc.2017.08.001
Ling DC, Bakkenist CJ, Ferris RL, Clump DA. Role of Immunotherapy in Head and Neck Cancer. Semin Radiat Oncol. 2018;28(1):12-16. https://doi.org/10.1016/j.semradonc.2017.08.009
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):559–97. https://doi.org/10.5858/arpa.2017-0286-CP
Harden ME, Munger K. Human papillomavirus molecular biology. Mutat Res Rev Mutat Res. 2017 Apr-Jun;772:3-12. https://doi.org/10.1016/j.mrrev.2016.07.002
Cosper PF, Bradley S, Luo L, Kimple RJ. Biology of HPV Mediated Carcinogenesis and Tumor Progression. Semin Radiat Oncol. 2021 Oct;31(4):265-273. https://doi.org/10.1016/j.semradonc.2021.02.006
Sanjuán R, Pereira-Gómez M, Risso J, Chapter 3 - Genome Instability in DNA Viruses, Genome Stability, From Virus to Human Application. Academic Press. 2016, Pages 37-47, ISBN 9780128033098. https://doi.org/10.1016/B978-0-12-803309-8.00003-3
Vande Pol SB, Klingelhutz AJ. Papillomavirus E6 oncoproteins. Virology. 2013;445(1-2):115-137. https://doi.org/10.1016/j.virol.2013.04.026
Kono T, Laimins L. Genomic Instability and DNA Damage Repair Pathways Induced by Human Papillomaviruses. Viruses. 2021; 13(9):1821. https://doi.org/10.3390/v13091821
Westrich JA, Warren CJ, Pyeon D. Evasion of host immune defenses by human papillomavirus. Virus Res. 2017 Mar 2;231:21-33. https://doi.org/10.1016/j.virusres.2016.11.023
Liu C, Lu J, Tian H, et al. Increased expression of PD‑L1 by the human papillomavirus 16 E7 oncoprotein inhibits anticancer immunity. Mol Med Rep. 2017;15(3):1063-1070. https://doi.org/10.3892/mmr.2017.6102
Hong AM, Ferguson P, Dodds T, et al. Significant association of PD-L1 expression with human papillomavirus positivity and its prognostic impact in oropharyngeal cancer. Oral Oncol. 2019;92:33-39. https://doi.org/10.1016/j.oraloncology.2019.03.012
Salmaninejad A, Khoramshahi V, Azani A, et al. PD-1 and cancer: molecular mechanisms and polymorphisms. Immunogenetics. 2018 Feb;70(2):73-86. https://doi.org/10.1007/s00251-017-1015-5
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