LACK OF CORRELATION BETWEEN HUMAN PAPILLOMAVIRUS AND NASOPHARYNGEAL CANCER: A COMPREHENSIVE ASSESSMENT THROUGH SYSTEMATIC META-ANALYSIS

Main Article Content

Tang Xiangping
Jamal Muhammad Khan
Syeda Saba Sajjad
Sobia Khwaja
Yi Yongxiang
Li Junwei

Keywords

Nasopharyngeal cancer (NPC), Bradford Hill criteria, Human papillomavirus (HPV)

Abstract

Objectives: Decoding the involvement of human papillomavirus (HPV) in nasopharyngeal cancer (NPC) has yielded contradictory findings worldwide. Despite various statistical meta-analyses exploring this association, controversy persists due to inherent limitations of meta-analysis. In this study, we aimed to investigate the potential link between HPV and NPC using an alternative method, the Bradford Hill criteria, to provide a clearer perspective.


Methods: PubMed was utilized to extract studies associating HPV with NPC. We evaluated the potential association using the Bradford Hill criteria postulates, scrutinizing available data on HPV in NPC and normal/benign samples. Rigorous assessment of study methodologies enhanced the authenticity of our findings, considering the possibility of false-negative and false-positive results.


Results: A comprehensive evaluation against Bradford Hill criteria revealed unfulfilled major postulates, including strength, temporality, consistency, plausibility, biological gradient, experiment, specificity, and analogy.


Conclusion: Our findings suggest no causal association between HPV and NPC.

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References

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D. Global cancer statistics. CA: a cancer journal for clinicians 2011; 61: 69-90.
2. Khan M and Hameed Y. Discovery of novel six genes-based cervical cancer-associated biomarkers that are capable to break the heterogeneity barrier and applicable at the global level. Journal of Cancer Research and Therapeutics 2023;
3. Yasir M, Nawaz A, Ghazanfar S, Okla M, Chaudhary A, Al WH, Ajmal M, AbdElgawad H, Ahmad Z and Abbas F. Anti-bacterial activity of essential oils against multidrug-resistant foodborne pathogens isolated from raw milk. Brazilian Journal of Biology 2022; 84: e259449.
4. Parkin D and Muir C. Cancer Incidence in Five Continents. Comparability and quality of data. IARC scientific publications 1992; 45-173.
5. Zhang L, Sahar A, Li C, Chaudhary A, Yousaf I, Saeedah M, Mubarak A, Haris M, Nawaz M and Reem M. A detailed multi-omics analysis of GNB2 gene in human cancers. Brazilian Journal of Biology 2022; 84:
6. Robinson M, Suh Y-e, Paleri V, Devlin D, Ayaz B, Pertl L and Thavaraj S. Oncogenic human papillomavirus-associated nasopharyngeal carcinoma: an observational study of correlation with ethnicity, histological subtype and outcome in a UK population. Infectious Agents and Cancer 2013; 8: 30.
7. Giannoudis A, Ergazaki M, Segas J, Giotakis J, Adamopoulos G, Gorgoulis V and Spandidos D. Detection of Epstein-Barr virus and human papillomavirus in nasopharyngeal carcinoma by the polymerase chain reaction technique. Cancer letters 1995; 89: 177-181.
8. Hameed Y and Ejaz S. TP53 lacks tetramerization and N-terminal domains due to novel inactivating mutations detected in leukemia patients. Journal of Cancer Research and Therapeutics 2021; 17: 931-937.
9. Punwaney R, Brandwein MS, Zhang DY, Urken ML, Cheng R, Park CS, Li HB, Li XJH, Sciences NJft, Head Sot and Neck. Human papillomavirus may be common within nasopharyngeal carcinoma of Caucasian Americans: investigation of Epstein‐Barr virus and human papillomavirus in eastern and western nasopharyngeal carcinoma using ligation‐dependent polymerase chain reaction. 1999; 21: 21-29.
10. Rassekh CH, Rady PL, Arany I, Tyring SK, Knudsen S, Calhoun KH, Seikaly H and Bailey BJJTL. Combined Epstein‐Barr virus and human papillomavirus infection in nasopharyngeal carcinoma. 1998; 108: 362-367.
11. Laantri N, Attaleb M, Kandil M, Naji F, Mouttaki T, Dardari Rk, Belghmi K, Benchakroun N, El Mzibri M, Khyatti MJIa and cancer. Human papillomavirus detection in moroccan patients with nasopharyngeal carcinoma. 2011; 6: 1-6.
12. Maruyama H, Yasui T, Ishikawa‐Fujiwara T, Morii E, Yamamoto Y, Yoshii T, Takenaka Y, Nakahara S, Todo T and Hongyo TJCs. Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population. 2014; 105: 409-417.
13. Verma V, Simone CB, Lin CJH and neck. Human papillomavirus and nasopharyngeal cancer. 2018; 40: 696-706.
14. Barwad A, Sood S, Gupta N, Rajwanshi A, Panda N and Srinivasan RJDc. Human papilloma virus associated head and neck cancer: a PCR based study. 2012; 40: 893-897.
15. Yang F, Huang S, Wang M, Li J, Chen XJLCebyhtJwkzzJoCO, Head, and Surgery N. The correlation of human papillomavirus and EB virus infection in nasopharyngeal carcinoma in Fujian. 2014; 28: 1122-1125.
16. Tung Y-C, Lin K-H, Chu P-Y, Hsu C and Kuo W-RJTKjoms. Detection of human papilloma virus and Epstein-Barr virus DNA in nasopharyngeal carcinoma by polymerase chain reaction. 1999; 15: 256-262.
17. Lopez-Lizarraga E, Sanchez-Corona J, Montoya-Fuentes H, Bravo-Cuellar A, Campollo-Rivas O, Lopez-Demerutis E, Morgan-Villela G, Arcaute-Velazquez F, Monreal-Martinez JA, Troyo RJE, nose and journal t. Human papillomavirus in tonsillar and nasopharyngeal carcinoma: isolation of HPV subtype 31. 2000; 79: 942-944.
18. Giannoudis A, Ergazaki M, Segas J, Giotakis J, Adamopoulos G, Gorgoulis V and Spandidos DJCl. Detection of Epstein-Barr virus and human papillomavirus in nasopharyngeal carcinoma by the polymerase chain reaction technique. 1995; 89: 177-181.
19. Atighechi S, Ahmadpour BM, Mirvakili S, Sheikhha M, Baradaranfar M, Dadgarnia M and Behniafard NJEo. Human papilloma virus and nasopharyngeal carcinoma: pathology, prognosis, recurrence and mortality of the disease. 2014; 215-216.
20. Dickens P, Srivastava G and Liu YT. Human papillomavirus 16/18 and nasopharyngeal carcinoma. 1992; 45: 81-82.
21. Asante D-B, Asmah RH, Adjei AA, Kyei F, Simpong DL, Brown CA and Gyasi RKJTSWJ. Detection of human papillomavirus genotypes and epstein-barr virus in nasopharyngeal carcinomas at the korle-bu teaching hospital, Ghana. 2017; 2017:
22. Sekee TR, Burt FJ, Goedhals D, Goedhals J, Munsamy Y and Seedat RYJPR. Human papillomavirus in head and neck squamous cell carcinomas in a South African cohort. 2018; 6: 58-62.
23. Stenmark MH, McHugh JB, Schipper M, Walline HM, Komarck C, Feng FY, Worden FP, Wolf GT, Chepeha DB and Prince MEJIJoROBP. Nonendemic HPV-positive nasopharyngeal carcinoma: association with poor prognosis. 2014; 88: 580-588.
24. Maxwell JH, Kumar B, Feng FY, McHugh JB, Cordell KG, Eisbruch A, Worden FP, Wolf GT, Prince ME, Moyer JSJH and neck. HPV‐positive/p16‐positive/EBV‐negative nasopharyngeal carcinoma in white North Americans. 2010; 32: 562-567.
25. Lo EJ, Bell D, Woo JS, Li G, Hanna EY, El‐Naggar AK and Sturgis EMJTL. Human papillomavirus and WHO type I nasopharyngeal carcinoma. 2010; 120: 1990-1997.
26. Walline HM, Komarck C, McHugh JB, Byrd SA, Spector ME, Hauff SJ, Graham MP, Bellile E, Moyer JS, Prince MEJJoh and surgery n. High-risk human papillomavirus detection in oropharyngeal, nasopharyngeal, and oral cavity cancers: comparison of multiple methods. 2013; 139: 1320-1327.
27. Fakhry C, Westra WH, Wang SJ, van Zante A, Zhang Y, Rettig E, Yin LX, Ryan WR, Ha PK and Wentz AJC. The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer. 2017; 123: 1566-1575.
28. Wilson DD, Crandley EF, Sim A, Stelow EB, Majithia N, Shonka DC, Jameson MJ, Levine PA, Read PWJJOH and Surgery N. Prognostic significance of p16 and its relationship with human papillomavirus in pharyngeal squamous cell carcinomas. 2014; 140: 647-653.
29. Dogan S, Hedberg ML, Ferris RL, Rath TJ, Assaad AM, Chiosea SIJH and neck. Human papillomavirus and Epstein–Barr virus in nasopharyngeal carcinoma in a low‐incidence population. 2014; 36: 511-516.
30. Robinson M, Suh Y-e, Paleri V, Devlin D, Ayaz B, Pertl L, Thavaraj SJIa and cancer. Oncogenic human papillomavirus-associated nasopharyngeal carcinoma: an observational study of correlation with ethnicity, histological subtype and outcome in a UK population. 2013; 8: 1-7.
31. Simon J, Schroeder L, Ingarfield K, Diehl S, Werner J, Brenner N, Liu Z, Pawlita M, Pring M and Butt JJIjoc. Epstein‐Barr virus and human papillomavirus serum antibodies define the viral status of nasopharyngeal carcinoma in a low endemic country. 2020; 147: 461-471.
32. Lin Z, Khong B, Kwok S, Cao H, West RB, Le QT, Kong CSJH and neck. Human papillomavirus 16 detected in nasopharyngeal carcinomas in white Americans but not in endemic Southern Chinese patients. 2014; 36: 709-714.
33. Kano M, Kondo S, Wakisaka N, Moriyama-Kita M, Nakanishi Y, Endo K, Murono S, Nakamura H and Yoshizaki TJANL. The influence of human papillomavirus on nasopharyngeal carcinoma in Japan. 2017; 44: 327-332.
34. Deng Z, Hasegawa M, Aoki K, Matayoshi S, Kiyuna A, Yamashita Y, Uehara T, Agena S, Maeda H and Xie MJIjoo. A comprehensive evaluation of human papillomavirus positive status and p16INK4a overexpression as a prognostic biomarker in head and neck squamous cell carcinoma. 2014; 45: 67-76.
35. Ruuskanen M, Irjala H, Minn H, Vahlberg T, Randen‐Brady R, Hagström J, Syrjänen S, Leivo IJH and neck. Epstein‐Barr virus and human papillomaviruses as favorable prognostic factors in nasopharyngeal carcinoma: a nationwide study in Finland. 2019; 41: 349-357.
36. Huang C-C, Hsiao J-R, Yang M-W, Wu Y-H, Hsu K-F, Chang Y, Chen C-W, Tsai S-T, Wei H-P and Jin Y-TJJocp. Human papilloma virus detection in neoplastic and non-neoplastic nasopharyngeal tissues in Taiwan. 2011; 64: 571-577.
37. Jiang L, Caifeng L, Hongyi L and Chen HJAJoSMMU. Expression of E6 oncoprotein of HPV16, cyclin D_1, and human telomerase transcriptase in nasopharyngeal carcinoma tissues and its significance. 1999;
38. Svajdler Jr M, Kaspirkova J, Mezencev R, Laco J, Torday T, Dubinsky P, Straka L, Ondic O, Michal M and Skalova AJN. Human papillomavirus and Epstein-Barr virus in nasopharyngeal carcinoma in a non-endemic eastern european population. 2016; 63: 107-114.
39. Mirzamani N, Salehian P, Farhadi MJE and pathology m. Detection of EBV and HPV in nasopharyngeal carcinoma by in situ hybridization. 2006; 81: 231-234.
40. Hørding U, Nielsen HW, Daugaard S and Albeck HJTL. Human papillomavirus types 11 and 16 detected in nasopharyngeal carcinomas by the polymerase chain reaction. 1994; 104: 99-102.
41. Doğan HT, Kılıçarslan A, Doğan M, Süngü N, Tezel GG, Güler GJP-R and Practice. Retrospective analysis of oncogenic human papilloma virus and Epstein-Barr virus prevalence in Turkish nasopharyngeal cancer patients. 2016; 212: 1021-1026.
42. Altekin I, Taş A, Yalcin O, Guven SG, Aslan Z, Adali MK and Karasalihoğlu ARJEAoO-R-L. Frequency of Epstein–Barr virus and human papilloma virus in patients with nasopharyngeal carcinoma. 2020; 1-7.
43. Kang H, Kwon M, Park JJ, Kim JP, Woo SH, Ahn S-K, Lee JS, Seo JH and Hwa JSJOo. Clinical implications of human papilloma virus and other biologic markers in nasopharyngeal cancer. 2016; 55: e7-e10.
44. Narisawa‐Saito M and Kiyono T. Basic mechanisms of high‐risk human papillomavirus‐induced carcinogenesis: Roles of E6 and E7 proteins. Cancer science 2007; 98: 1505-1511.
45. Malik SS, Batool R, Masood N and Yasmin A. Risk factors for prostate cancer: A multifactorial case-control study. Curr Probl Cancer 2018; 42: 337-343.
46. Whitaker NJ, Glenn WK, Sahrudin A, Orde MM, Delprado W and Lawson JS. Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer. The Prostate 2013; 73: 236-241.
47. Anzivino E, Rodio DM, Mischitelli M, Bellizzi A, Sciarra A, Salciccia S, Gentile V and Pietropaolo V. High frequency of JCV DNA detection in prostate cancer tissues. Cancer Genomics-Proteomics 2015; 12: 189-200.
48. Zammarchi F, Pistello M, Piersigilli A, Murr R, Cristofano CD, Naccarato AG and Bevilacqua G. MMTV‐like sequences in human breast cancer: a fluorescent PCR/laser microdissection approach. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland 2006; 209: 436-444.
49. Al Dossary R, Alkharsah KR and Kussaibi H. Prevalence of Mouse Mammary Tumor Virus (MMTV)-like sequences in human breast cancer tissues and adjacent normal breast tissues in Saudi Arabia. BMC cancer 2018; 18: 1-10.
50. Hameed Y, Usman M, Liang S and Ejaz S. Novel diagnostic and prognostic biomarkers of colorectal cancer: capable to overcome the heterogeneity-specific barrier and valid for global applications. Plos one 2021; 16: e0256020.
51. Zhu X, Tang L, Mao J, Hameed Y, Zhang J, Li N, Wu D, Huang Y and Li C. Decoding the mechanism behind the pathogenesis of the focal segmental glomerulosclerosis. Computational and Mathematical Methods in Medicine 2022:
52. Usman M, Hameed Y, Ahmad M, Rehman JU, Ahmed H, Hussain MS, Asif R, Murtaza MG, Jawad MT and Iqbal MJ. Breast cancer risk and human papillomavirus infection: a Bradford Hill criteria based evaluation. Infectious Disorders-Drug Targets (Formerly Current Drug Targets-Infectious Disorders) 2022; 22: 41-50.
53. Hameed Y, Usman M and Ahmad M. Does mouse mammary tumor-like virus cause human breast cancer? Applying Bradford Hill criteria postulates. Bulletin of the National Research Centre 2020; 44: 1-13.
54. Awadh A, Chughtai AA, Dyda A, Sheikh M, Heslop DJ and MacIntyre CR. Does Zika virus cause microcephaly-applying the Bradford Hill viewpoints. PLoS currents 2017; 9:
55. Song D, Li H, Li H and Dai J. Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer. Oncology letters 2015; 10: 600-606.

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