Human papillomavirus infection and its association with lung cancer: a case-control study (2011–2019)
Abstract
Background and Objectives: Human papillomavirus (HPV) causes about 4.5% of all new human cancers. The purpose of this study was to look into the prevalence of various HPV types in patients with lung cancer.
Materials and Methods: The study included a cohort of 61 individuals who had received treatment at Imam Khomeini Hospital in Ahvaz between 2011 and 2019. Paraffin-embedded tissues were used for molecular analysis. The primary goal was to assess the differences in HPV prevalence between lung cancer patients and a control group, using a Nested PCR assay followed by sequencing.
Results: Among the lung cancer patients, HPV DNA was detected in 10 individuals, while three individuals in the control group were also positive (16.3% versus 12.0%, P=0.65). Notably, every detected HPV variant was classified as the high-risk type 16. Additionally, the researchers investigated potential associations between age, sex, smoking habits, and lung cancer in both HPV-positive and negative patients. The study findings revealed that age, sex, and smoking habits did not show statistically significant associations with the presence of HPV (P>0.05). Moreover, Lung cancer incidence was not significantly correlated with HPV infection (P>0.05).
Conclusion: Therefore, according to the study's findings, smoking, HPV infection, and lung cancer prevalence were not significantly correlated in the population under investigation.
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7. McBride AA. Human papillomaviruses: diversity, infection and host interactions. Nat Rev Microbiol 2022; 20: 95-108.
8. Mehta K, Laimins L. High-Risk Human Papillomaviruses and DNA Repair. Recent Results Cancer Res 2021; 217: 141-155.
9. de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer 2017; 141: 664-670.
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11. Ferrari FA, Magni F, Bosco M, Biancotto G, Zorzato PC, Laganà AS, et al. The role of micronutrients in Human Papillomavirus infection, Cervical Dysplasia, and Neoplasm. Healthcare (Basel) 2023; 11: 1652.
12. Rai R, Nahar M, Jat D, Gupta N, Mishra SK. A systematic assessment of stress insomnia as the high-risk factor for cervical cancer and interplay of cervicovaginal microbiome. Front Cell Infect Microbiol 2022; 12: 1042663.
13. Dunne EF, Park IU. HPV and HPV-Associated Diseases. Infect Dis Clin North Am 2013; 27: 765-778.
14. Yu YQ, Hao JQ, Mendez MJG, Mohamed SB, Fu SL, Zhao FH, et al. The Prevalence of cervical HPV infection and genotype distribution in 856,535 Chinese women with normal and abnormal Cervical Lesions: A Systemic Review. J Cytol 2022; 39: 137-147.
15. Ebrahimi N, Yousefi Z, Khosravi G, Malayeri FE, Golabi M, Askarzadeh M, et al. Human papillomavirus vaccination in low- and middle-income countries: progression, barriers, and future prospective. Front Immunol 2023; 14: 1150238.
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17. Karnosky J, Dietmaier W, Knuettel H, Freigang V, Koch M, Koll F, et al. HPV and lung cancer: A systematic review and meta-analysis. Cancer Rep (Hoboken) 2021; 4(4): e1350.
18. Kontham SS, Walter CEJ, Raju M, Mohanapriya CD, Karuppasamy N, Shankaran ZS, et al. An Effective and viable DNA extraction protocol for FFPE tissues and its effect on downstream molecular application. Am J Biochem Biotechnol 2020; 16: 148-161.
19. Hearn RP, Arblaster KE. DNA extraction techniques for use in education. Biochem Mol Biol Educ 2010; 38: 161-166.
20. Pikor LA, Enfield KS, Cameron H, Lam WL. DNA Extraction from paraffin embedded material for genetic and epigenetic analyses. J Vis Exp 2011; (49): 2763.
21. Liu AW, Villar-Briones A, Luscombe NM, Plessy C. Automated phenol-chloroform extraction of high molecular weight genomic DNA for use in long-read single-molecule sequencing. F1000Res 2022; 11: 240.
22. Seiler C, Sharpe A, Barrett JC, Harrington EA, Jones EV, Marshall GB. Nucleic acid extraction from formalin-fixed paraffin-embedded cancer cell line samples: a tradeoff between quantity and quality? BMC Clin Pathol 2016; 16: 17.
23. Depuydt CE, Boulet GA, Horvath CA, Benoy IH, Vereecken AJ, Bogers JJ. Comparison of MY09/11 consensus PCR and type-specific PCRs in the detection of oncogenic HPV types. J Cell Mol Med 2007; 11: 881-891.
24. Nilyanimit P, Chansaenroj J, Poomipak W, Praianantathavorn K, Payungporn S, Poovorawan Y. Comparison of four human Papillomavirus Genotyping methods: Next-generation Sequencing, INNO-LiPA, Electrochemical DNA Chip, and Nested-PCR. Ann Lab Med 2018; 38: 139-146.
25. Lim YK, Choi JH, Park S, Kweon OJ, Park AJ. Comparison of three different commercial kits for the Human Papilloma Virus Genotyping. J Clin Lab Anal 2016; 30: 1110-1115.
26. Clifford GM, Vaccarella S, Franceschi S, Tenet V, Umulisa MC, Tshomo U, et al. Comparison of Two Widely Used Human Papillomavirus Detection and Genotyping Methods, GP5+/6+-Based PCR Followed by Reverse Line Blot Hybridization and Multiplex Type-Specific E7-Based PCR. J Clin Microbiol 2016; 54: 2031-2038.
27. Dastjerd NT, Abbasian L, Mohebbi SR, Banaem LM, Ashtiani MF, Rostamafshar Z, et al. Prevalence and distribution of human papillomavirus genotypes in women living with HIV: a cross-sectional study in Iran. BMC Infect Dis 2025; 25: 1471.
28. Bzhalava D, Eklund C, Dillner J. International standardization and classification of human papillomavirus types. Virology 2015; 476: 341-344.
29. Nakagawa T, Shigehara K, Kato Y, Kawaguchi S, Nakata H, Nakano T, et al. Are bladder washing samples suitable for investigation of HPV infection in urinary bladder? Comparison in HPV prevalence between urine and washing samples. J Med Virol 2023; 95(1): e28110.
30. Jiang YJ, Chao CC, Chang AC, Chen PC, Cheng FJ, Liu JF, et al. Cigarette smoke-promoted increases in osteopontin expression attract mesenchymal stem cell recruitment and facilitate lung cancer metastasis. J Adv Res 2022; 41: 77-87.
31. Li YJ, Tsai YC, Chen YC, Christiani DC. Human papilloma virus and female lung adenocarcinoma. Semin Oncol 2009; 36: 542-552.
32. Li M, Xu Y, Zhang Z, He Z, Yu X, Deng Z, et al. Association between human papillomavirus and EGFR mutations in advanced lung adenocarcinoma. Oncol Lett 2016; 12: 1953-1958.
33. He F, Xiong W, Yu F, Xiao R, Ye H, Li W, et al. Human papillomavirus infection maybe not associated with primary lung cancer in the Fujian population of China. Thorac Cancer 2020; 11: 561-569.
34. Anantharaman D, Gheit T, Waterboer T, Halec G, Carreira C, Abedi-Ardekani B, et al. No causal association identified for human papillomavirus infections in lung cancer. Cancer Res 2014; 74: 3525-3534.
35. Carpagnano GE, Koutelou A, Natalicchio MI, Martinelli D, Ruggieri C, Di Taranto A, et al. HPV in exhaled breath condensate of lung cancer patients. Br J Cancer 2011; 105: 1183-1190.
36. Giuliani L, Jaxmar T, Casadio C, Gariglio M, Manna A, D'Antonio D, et al. Detection of oncogenic viruses SV40, BKV, JCV, HCMV, HPV and p53 codon 72 polymorphism in lung carcinoma. Lung Cancer 2007; 57: 273-281.
37. Chiou HL, Wu MF, Liaw YC, Cheng YW, Wong RH, Chen CY, et al. The presence of Human Papillomavirus type 16/18 dna in blood circulation may act as a risk marker of lung cancer in taiwan. Cancer 2003; 97: 1558-1563.
38. Crusz SM, El-Shakankery K, Miller RE. Targeting hpv in gynaecological cancers – current status, ongoing challenges and future directions. Womens Health (Lond) 2020; 16: 1745506520961709.
39. Ragin C, Obikoya-Malomo M, Kim S, Chen Z, Flores-Obando R, Gibbs D, et al. HPV-associated lung cancers: an international pooled analysis. Carcinogenesis 2014; 35: 1267-1275.
40. Nie Z, Zhang K, Li Z, Bing X, Jin S, Li M. Human papillomavirus 16 E6 promotes angiogenesis of lung cancer via SNHG1. Cell Biochem Biophys 2023; 81: 325-336.
41. Argyri E, Tsimplaki E, Marketos C, Politis G, Panotopoulou E. Investigating the role of human papillomavirus in lung cancer. Papillomavirus Res 2017; 7-10.
42. Simen-Kapeu A, Surcel HM, Koskela P, Pukkala E, Lehtinen M. Lack of association between human papillomavirus type 16 and 18 infections and female lung cancer. Cancer Epidemiol Biomarkers Prev 2010; 19: 1879-1881.
43. Sirera G, Videla S, Saludes V, Castellà E, Sanz C, Ariza A, et al. Prevalence of HPV-DNA and E6 mRNA in lung cancer of HIV-infected patients. Sci Rep 2022; 12: 13196.
44. Park MS, Chang YS, Shin JH, Kim DJ, Chung KY, Shin DH, et al. The prevalence of human papillomavirus infection in Korean non-small cell lung cancer patients. Yonsei Med J 2007; 48: 69-77.
45. Badillo-Almaraz I, Zapata-Benavides P, Saavedra-Alonso S, Zamora-Avila D, Reséndez-Pérez D, Tamez-Guerra R, et al. Human papillomavirus 16/18 infections in lung cancer patients in Mexico. Intervirology 2013; 56: 310-315.
2. Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y. The new World Health Organization classification of lung tumours. Eur Respir J 2001; 18: 1059-1068.
3. Fol M, Koziński P, Kulesza J, Białecki P, Druszczyńska M. Dual Nature of Relationship between Mycobacteria and Cancer. Int J Mol Sci 2021; 22: 8332.
4. Prabhu PR, Jayalekshmi D, Pillai MR. Lung cancer and human papilloma viruses (HPVs): examining the molecular evidence. J Oncol 2012; 2012: 750270.
5. Klein F, Amin Kotb WF, Petersen I. Incidence of human papilloma virus in lung cancer. Lung Cancer 2009; 65: 13-18.
6. Li X, Ling Y, Hu L, Zhang L, Lin S, Zhang X, et al. Detection of Human papillomavirus DNA, E6/E7 messenger RNA, and p16INK4a in lung cancer: A Systematic review and Meta-analysis. J Infect Dis 2023; 228: 1137-1145.
7. McBride AA. Human papillomaviruses: diversity, infection and host interactions. Nat Rev Microbiol 2022; 20: 95-108.
8. Mehta K, Laimins L. High-Risk Human Papillomaviruses and DNA Repair. Recent Results Cancer Res 2021; 217: 141-155.
9. de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer 2017; 141: 664-670.
10. Shapshak P, Sinnott JT, Somboonwit C, Kuhn JH (2015). Global Virology I - Identifying and Investigating Viral Diseases. New York: Springer.
11. Ferrari FA, Magni F, Bosco M, Biancotto G, Zorzato PC, Laganà AS, et al. The role of micronutrients in Human Papillomavirus infection, Cervical Dysplasia, and Neoplasm. Healthcare (Basel) 2023; 11: 1652.
12. Rai R, Nahar M, Jat D, Gupta N, Mishra SK. A systematic assessment of stress insomnia as the high-risk factor for cervical cancer and interplay of cervicovaginal microbiome. Front Cell Infect Microbiol 2022; 12: 1042663.
13. Dunne EF, Park IU. HPV and HPV-Associated Diseases. Infect Dis Clin North Am 2013; 27: 765-778.
14. Yu YQ, Hao JQ, Mendez MJG, Mohamed SB, Fu SL, Zhao FH, et al. The Prevalence of cervical HPV infection and genotype distribution in 856,535 Chinese women with normal and abnormal Cervical Lesions: A Systemic Review. J Cytol 2022; 39: 137-147.
15. Ebrahimi N, Yousefi Z, Khosravi G, Malayeri FE, Golabi M, Askarzadeh M, et al. Human papillomavirus vaccination in low- and middle-income countries: progression, barriers, and future prospective. Front Immunol 2023; 14: 1150238.
16. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. IARC Monogr Eval Carcinog Risks Hum 2012; 100: 1-441.
17. Karnosky J, Dietmaier W, Knuettel H, Freigang V, Koch M, Koll F, et al. HPV and lung cancer: A systematic review and meta-analysis. Cancer Rep (Hoboken) 2021; 4(4): e1350.
18. Kontham SS, Walter CEJ, Raju M, Mohanapriya CD, Karuppasamy N, Shankaran ZS, et al. An Effective and viable DNA extraction protocol for FFPE tissues and its effect on downstream molecular application. Am J Biochem Biotechnol 2020; 16: 148-161.
19. Hearn RP, Arblaster KE. DNA extraction techniques for use in education. Biochem Mol Biol Educ 2010; 38: 161-166.
20. Pikor LA, Enfield KS, Cameron H, Lam WL. DNA Extraction from paraffin embedded material for genetic and epigenetic analyses. J Vis Exp 2011; (49): 2763.
21. Liu AW, Villar-Briones A, Luscombe NM, Plessy C. Automated phenol-chloroform extraction of high molecular weight genomic DNA for use in long-read single-molecule sequencing. F1000Res 2022; 11: 240.
22. Seiler C, Sharpe A, Barrett JC, Harrington EA, Jones EV, Marshall GB. Nucleic acid extraction from formalin-fixed paraffin-embedded cancer cell line samples: a tradeoff between quantity and quality? BMC Clin Pathol 2016; 16: 17.
23. Depuydt CE, Boulet GA, Horvath CA, Benoy IH, Vereecken AJ, Bogers JJ. Comparison of MY09/11 consensus PCR and type-specific PCRs in the detection of oncogenic HPV types. J Cell Mol Med 2007; 11: 881-891.
24. Nilyanimit P, Chansaenroj J, Poomipak W, Praianantathavorn K, Payungporn S, Poovorawan Y. Comparison of four human Papillomavirus Genotyping methods: Next-generation Sequencing, INNO-LiPA, Electrochemical DNA Chip, and Nested-PCR. Ann Lab Med 2018; 38: 139-146.
25. Lim YK, Choi JH, Park S, Kweon OJ, Park AJ. Comparison of three different commercial kits for the Human Papilloma Virus Genotyping. J Clin Lab Anal 2016; 30: 1110-1115.
26. Clifford GM, Vaccarella S, Franceschi S, Tenet V, Umulisa MC, Tshomo U, et al. Comparison of Two Widely Used Human Papillomavirus Detection and Genotyping Methods, GP5+/6+-Based PCR Followed by Reverse Line Blot Hybridization and Multiplex Type-Specific E7-Based PCR. J Clin Microbiol 2016; 54: 2031-2038.
27. Dastjerd NT, Abbasian L, Mohebbi SR, Banaem LM, Ashtiani MF, Rostamafshar Z, et al. Prevalence and distribution of human papillomavirus genotypes in women living with HIV: a cross-sectional study in Iran. BMC Infect Dis 2025; 25: 1471.
28. Bzhalava D, Eklund C, Dillner J. International standardization and classification of human papillomavirus types. Virology 2015; 476: 341-344.
29. Nakagawa T, Shigehara K, Kato Y, Kawaguchi S, Nakata H, Nakano T, et al. Are bladder washing samples suitable for investigation of HPV infection in urinary bladder? Comparison in HPV prevalence between urine and washing samples. J Med Virol 2023; 95(1): e28110.
30. Jiang YJ, Chao CC, Chang AC, Chen PC, Cheng FJ, Liu JF, et al. Cigarette smoke-promoted increases in osteopontin expression attract mesenchymal stem cell recruitment and facilitate lung cancer metastasis. J Adv Res 2022; 41: 77-87.
31. Li YJ, Tsai YC, Chen YC, Christiani DC. Human papilloma virus and female lung adenocarcinoma. Semin Oncol 2009; 36: 542-552.
32. Li M, Xu Y, Zhang Z, He Z, Yu X, Deng Z, et al. Association between human papillomavirus and EGFR mutations in advanced lung adenocarcinoma. Oncol Lett 2016; 12: 1953-1958.
33. He F, Xiong W, Yu F, Xiao R, Ye H, Li W, et al. Human papillomavirus infection maybe not associated with primary lung cancer in the Fujian population of China. Thorac Cancer 2020; 11: 561-569.
34. Anantharaman D, Gheit T, Waterboer T, Halec G, Carreira C, Abedi-Ardekani B, et al. No causal association identified for human papillomavirus infections in lung cancer. Cancer Res 2014; 74: 3525-3534.
35. Carpagnano GE, Koutelou A, Natalicchio MI, Martinelli D, Ruggieri C, Di Taranto A, et al. HPV in exhaled breath condensate of lung cancer patients. Br J Cancer 2011; 105: 1183-1190.
36. Giuliani L, Jaxmar T, Casadio C, Gariglio M, Manna A, D'Antonio D, et al. Detection of oncogenic viruses SV40, BKV, JCV, HCMV, HPV and p53 codon 72 polymorphism in lung carcinoma. Lung Cancer 2007; 57: 273-281.
37. Chiou HL, Wu MF, Liaw YC, Cheng YW, Wong RH, Chen CY, et al. The presence of Human Papillomavirus type 16/18 dna in blood circulation may act as a risk marker of lung cancer in taiwan. Cancer 2003; 97: 1558-1563.
38. Crusz SM, El-Shakankery K, Miller RE. Targeting hpv in gynaecological cancers – current status, ongoing challenges and future directions. Womens Health (Lond) 2020; 16: 1745506520961709.
39. Ragin C, Obikoya-Malomo M, Kim S, Chen Z, Flores-Obando R, Gibbs D, et al. HPV-associated lung cancers: an international pooled analysis. Carcinogenesis 2014; 35: 1267-1275.
40. Nie Z, Zhang K, Li Z, Bing X, Jin S, Li M. Human papillomavirus 16 E6 promotes angiogenesis of lung cancer via SNHG1. Cell Biochem Biophys 2023; 81: 325-336.
41. Argyri E, Tsimplaki E, Marketos C, Politis G, Panotopoulou E. Investigating the role of human papillomavirus in lung cancer. Papillomavirus Res 2017; 7-10.
42. Simen-Kapeu A, Surcel HM, Koskela P, Pukkala E, Lehtinen M. Lack of association between human papillomavirus type 16 and 18 infections and female lung cancer. Cancer Epidemiol Biomarkers Prev 2010; 19: 1879-1881.
43. Sirera G, Videla S, Saludes V, Castellà E, Sanz C, Ariza A, et al. Prevalence of HPV-DNA and E6 mRNA in lung cancer of HIV-infected patients. Sci Rep 2022; 12: 13196.
44. Park MS, Chang YS, Shin JH, Kim DJ, Chung KY, Shin DH, et al. The prevalence of human papillomavirus infection in Korean non-small cell lung cancer patients. Yonsei Med J 2007; 48: 69-77.
45. Badillo-Almaraz I, Zapata-Benavides P, Saavedra-Alonso S, Zamora-Avila D, Reséndez-Pérez D, Tamez-Guerra R, et al. Human papillomavirus 16/18 infections in lung cancer patients in Mexico. Intervirology 2013; 56: 310-315.
| Files | ||
| Issue | Vol 17 No 6 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i6.20372 | |
| Keywords | ||
| Human papillomaviruses Lung neoplasms Polymerase chain reaction Tissues Iran | ||
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How to Cite
1.
Shakeri Z, Makvandi M, Mirzaei H, Kanani M, Jalilian S. Human papillomavirus infection and its association with lung cancer: a case-control study (2011–2019). Iran J Microbiol. 2025;17(6):1033-1041.
