Mối liên quan giữa Human Papillomavirus với biểu hiện P16, P53, PRB ở bệnh nhân ung thư biểu mô tế bào gai vùng khẩu hầu
Nội dung chính của bài viết
Tóm tắt
Virus gây u nhú ở người type nguy cơ cao (High-risk human papillomavirus (HR-HPV)) là một trong các nguyên nhân gây ung thư khẩu hầu được ghi nhận gia tăng ở nhiều quần thể. Nghiên cứu này nhằm xác định tỷ lệ nhiễm HR-HPV, sự biểu hiện các protein p16, p53, pRb và mối liên quan giữa HR-HPV với p16, p53, pRb trên bệnh nhân ung thư biểu mô tế bào gai khẩu hầu. Mô tả cắt ngang 146 bệnh nhân, dùng real-time PCR để xác định các type HR-HPV và nhuộm hóa mô miễn dịch để khảo sát biểu hiện p16, p53, pRb trên mô FFPE. Tuổi trung bình: 58,3. Nam giới chiếm 89%. U thường gặp nhất ở amiđan (48,6%). Giai đoạn IV chiếm 80,8%. HR-HPV(+) là 63,7%, trong đó HPV16 là 77,4%. Tỷ lệ p16(+) là 43,2%, p53(-) là 74,7%, pRb(-) là 61,0%. Có mối liên quan giữa HR-HPV với p16 và p53 (p = 0,04 và p = 0,009).
Chi tiết bài viết
Từ khóa
Ung thư biểu mô tế bào gai vùng khẩu hầu, HR-HPV, p16, p53, pRb
Tài liệu tham khảo
2. Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J, Sasaki C, Joe J, Camp RL, Rimm DL, Psyrri A. Molecular classification identifies a subset of human papillomavirus-associated oropharyngeal cancers with favorable prognosis. J Clin Oncol. 2006 Feb 10; 24(5): 736-47. doi: 10.1200/JCO.2004.00.3335. Epub 2006 Jan 9. PMID: 16401683.
3. Plath M, Broglie MA, Förbs D, Stoeckli SJ, Jochum W. Prognostic significance of cell cycle-associated proteins p16, pRB, cyclin D1 and p53 in resected oropharyngeal carcinoma. Journal of Otolaryngology - Head & Neck Surgery. 2018; 47(1). doi:10.1186/s40463-018-0298-3.
4. Benzerdjeb N, Tantot J, Blanchet C, Philouze P, Mekki Y, Lopez J, Devouassoux-Shisheboran M. Oropharyngeal squamous cell carcinoma: p16/p53 immunohistochemistry as a strong predictor of HPV tumour status. Histopathology. 2021 Sep; 79(3): 381-390. doi: 10.1111/his.14350. Epub 2021 May 7. PMID: 33560536.
5. Jiromaru R, Yamamoto H, Yasumatsu R, Hongo T, Nozaki Y, Nakano T, Hashimoto K, Nakagawa T, Oda Y. p16 overexpression and Rb loss correlate with high-risk HPV infection in oropharyngeal squamous cell carcinoma. Histopathology. 2021 Sep; 79(3): 358-369. doi: 10.1111/his.14337. Epub 2021 May 6. PMID: 33450095.
6. Zumsteg ZS, Luu M, Rosenberg PS, et al. Global epidemiologic patterns of oropharyngeal cancer incidence trends. J Natl Cancer Inst. 2023 Dec 6; 115(12): 1544-1554. doi: 10.1093/jnci/djad169. PMID: 37603716; PMCID: PMC10699798.
7. Saiya P, Jantharapattana K, Dechaphunkul A, et al. HPV-Related Oropharyngeal Cancer in Southern Thailand: Proportion Trend and Survival Outcome. Asian Pac J Cancer Prev. 2024 Jan 1; 25(1): 57-64. doi: 10.31557/APJCP.2024.25.1.57. PMID: 38285767; PMCID: PMC10911748.
8. Saito Y, Hayashi R, Iida Y, et al. Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan. Cancer. 2020 Sep 15; 126(18): 4177-4187. doi: 10.1002/cncr.33062. Epub 2020 Jul 10. PMID: 32648953.
9. Budrukkar, A., Kashid, S.R., Swain, M. et al. Long-term outcomes of consecutive patients of oropharyngeal cancer treated with radical radiotherapy. BJC Rep 3, 54 (2025). https://doi.org/10.1038/s44276-025-00164-z.
10. Hung NV, Viet NH, Duc DT, Dieu TT, Binh NT, Hoang LH, Trung NQ. Analysis of HPV and NKG2D rs1049174 Polymorphism in Vietnamese Patients With Oropharyngeal Squamous Cell Carcinoma. Cancer Control. 2025 Jan-Dec; 32:10732748251362943. doi: 10.1177/10732748251362943. Epub 2025 Aug 12. PMID: 40795938; PMCID: PMC12344339.
11. Kouka M, Gerlach L, Büntzel J, Kaftan H, Böger D, Müller AH, Ernst T, Guntinas-Lichius O. Impact of Human Papillomavirus-Negative Dominance in Oropharyngeal Cancer on Overall Survival: A Population-Based Analysis in Germany from 2018 to 2020. Cancers (Basel). 2023 Nov 2; 15(21):5259. doi: 10.3390/cancers15215259. PMID: 37958431; PMCID: PMC10650408.
12. Youssef I, Yoon J, Mohamed N, et al. Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Oropharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy. JAMA Netw Open. 2022 Nov 1; 5(11): e2241538. doi: 10.1001/jamanetworkopen.2022.41538. Erratum in: JAMA Netw Open. 2022 Dec 1; 5(12): e2250485. doi: 10.1001/jamanetworkopen.2022.50485. PMID: 36367724; PMCID: PMC9652753.
13. Kim SI, Lee JW, Eun YG, Lee YC. A SEER-based analysis of trends in HPV-associated oropharyngeal squamous cell carcinoma. Infect Agent Cancer. 2024 Jun 28; 19(1): 29. doi: 10.1186/s13027-024-00592-5. PMID: 38943144; PMCID: PMC11214209.
14. Faraji F, Zaidi M, Fakhry C, Gaykalova DA. Molecular mechanisms of human papillomavirus-related carcinogenesis in head and neck cancer. Microbes Infect. 2017 Sep-Oct; 19(9-10): 464-475. doi: 10.1016/j.micinf.2017.06.001. Epub 2017 Jun 12. PMID: 28619685; PMCID: PMC5603399.
15. Bosshart SL, Morand GB, Broglie MA. Frequency and Localization of Second Primary Tumors in Patients with Oropharyngeal Carcinoma-The Influence of the Human Papilloma Virus. Cancers. 2021; 13(8): 1755. https://doi.org/10.3390/cancers13081755.
16. Psyrri A, Psychogios G, Kyrodimos E, Constantinidis J, Agelaki S, Boukovinas I, Lygeros S, Ploiarchopoulou K, Spathis A, Economopoulou P, Litsou E, Dimitriadis I, Athanasopoulos C, Zioga S, Trimis G, Poughias L, Panayiotides I. Evaluation of the attributable fraction and burden of HPV-related oropharyngeal cancers in Greece-the ORPHEAS study. ESMO Open. 2024 Oct; 9(10): 103724. doi: 10.1016/j.esmoop.2024.103724. Epub 2024 Sep 18. PMID: 39298992; PMCID: PMC11426035.
17. Oliva C, Carrillo-Beltrán D, Boettiger P, Gallegos I, Aguayo F. Human Papillomavirus Detected in Oropharyngeal Cancers from Chilean Subjects. Viruses. 2022; 14(6): 1212. https://doi.org/10.3390/v14061212.
18. Guarda V, Schroeder L, Pawlita M, Ikenberg K, Rupp NJ, Jochum W, Stoeckli SJ, Holzinger D and Broglie MA. Prevalence of Transcriptionally Active HPV Infection in Tumor-Free Oropharyngeal Tissue of OPSCC-Patients. Front. Oncol. 2022; 12:835814. doi: 10.3389/fonc.2022.835814.
19. Shaikh MH, McMillan NA, Johnson NW. HPV-associated head and neck cancers in the Asia Pacific: A critical literature review & meta-analysis. Cancer Epidemiol. 2015 Dec; 39(6): 923-38. doi: 10.1016/j.canep.2015.09.013. Epub 2015 Nov 9. PMID: 26523982.
20. Smith EM, Rubenstein LM, Henry H, et al. Human papillomavirus, p16 and p53 expression associated with survival of head and neck cancer. Infectious agents and cancer. 2010; 5: 4. doi: 10.1186/1750-9378-5-4.
21. Lewis JS Jr, Beadle B, Bishop JA, Chernock RD, Colasacco C, Lacchetti C, Moncur JT, Rocco JW, Schwartz MR, Seethala RR, Thomas NE, Westra WH, Faquin WC. Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists. Arch Pathol Lab Med. 2018 May; 142(5): 559-597. doi: 10.5858/arpa.2017-0286-CP. Epub 2017 Dec 18. PMID: 29251996.
22. Shinohara S, Kikuchi M, Tona R, et al. Prognostic impact of p16 and p53 expression in oropharyngeal squamous cell carcinomas. Japanese journal of clinical oncology. 2014 Mar; 44(3): 232-40. doi: 10.1093/jjco/hyt223.