Association between human papillomavirus and EGFR mutations in advanced lung adenocarcinoma

Li,Ming; Deng,Fang; Qian,Li‑Ting; Meng,Shui‑Ping; Zhang,Yang; Shan,Wu‑Lin; Zhang,Xiao‑Lei; Wang,Bao‑Long

doi:10.3892/ol.2016.4847

Association between human papillomavirus and EGFR mutations in advanced lung adenocarcinoma

Authors:
- Ming Li
- Fang Deng
- Li‑Ting Qian
- Shui‑Ping Meng
- Yang Zhang
- Wu‑Lin Shan
- Xiao‑Lei Zhang
- Bao‑Long Wang
View Affiliations

Affiliations: Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230001, P.R. China, Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, Anhui 230031, P.R. China, Department of Respiratory Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui 230031, P.R. China
Published online on: July 12, 2016 https://doi.org/10.3892/ol.2016.4847
Pages: 1953-1958

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Previous studies have demonstrated an association between human papillomavirus (HPV) and mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer patients; however, few studies have investigated this association in advanced lung adenocarcinoma patients undergoing gefitinib treatment. The present study investigated the association between HPV and EGFR mutations in advanced lung adenocarcinoma patients. A total of 95 advanced lung adenocarcinoma patients were enrolled in the study. The HPV infection status and presence of EGFR mutations in tumor tissue was evaluated. Patient clinical characteristics were also determined and compared with HPV infection and EGFR mutation status to analyze their impact on progression‑free survival. HPV DNA was identified in 27/95 (28.4%) lung adenocarcinoma tumors and was most common in patients with lymph node metastasis (P=0.016). A total of 44/95 (46.3%) cases exhibited EGFR mutations, which were predominantly observed in female patients and non‑smokers. The presence of HPV DNA was significantly associated with EGFR mutations (P=0.012) and multivariate analysis also revealed that HPV DNA was significantly associated with EGFR mutations (odds ratio=3.971) in advanced lung adenocarcinoma. Patients with both HPV infections and EGFR mutations exhibit a marked decrease in the risk of lung cancer progression when compared with those without HPV infection or EGFR mutations (adjusted HR=0.640; 95% confidence interval: 0.488‑0.840; P=0.001). HPV infection was significantly associated with EGFR mutations in advanced lung adenocarcinoma patients. Furthermore, patients with HPV infections exhibited the longest progression-free survival times, which may be due to good response to tyrosine kinase inhibitor‑ or platinum‑based‑adjuvant therapy in these patients. Patients with EGFR mutations exhibited a better prognosis when compared with those exhibiting wild-type EGFR, regardless of HPV status.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Thun MJ, Hannan LM, Adams-Campbell LL, Boffetta P, Buring JE, Feskanich D, Flanders WD, Jee SH, Katanoda K, Kolonel LN, et al: Lung cancer occurrence in never-smokers: An analysis of 13 cohorts and 22 cancer registry studies. PLoS Med. 5:e1852008. View Article : Google Scholar : PubMed/NCBI
3	Klein F, Amin Kotb WF and Petersen I: Incidence of human papilloma virus in lung cancer. Lung Cancer. 65:13–18. 2009. View Article : Google Scholar : PubMed/NCBI
4	Yanagawa N, Wang A, Kohler D, Santos Gda C, Sykes J, Xu J, Pintilie M and Tsao MS: Human papilloma virus genome is rare in North American non-small cell lung carcinoma patients. Lung Cancer. 79:215–220. 2013. View Article : Google Scholar : PubMed/NCBI
5	Sagerup CM, Nymoen DA, Halvorsen AR, Lund-Iversen M, Helland A and Brustugun OT: Human papilloma virus detection and typing in 334 lung cancer patients. Acta Oncol. 53:952–957. 2014. View Article : Google Scholar : PubMed/NCBI
6	Sarchianaki E, Derdas SP, Ntaoukakis M, Vakonaki E, Lagoudaki ED, Lasithiotaki I, Sarchianaki A, Koutsopoulos A, Symvoulakis EK, Spandidos DA, et al: Detection and genotype analysis of human papillomavirus in non-small cell lung cancer patients. Tumour Biol. 35:3203–3209. 2014. View Article : Google Scholar : PubMed/NCBI
7	Anantharaman D, Gheit T, Waterboer T, Halec G, Carreira C, Abedi-Ardekani B, McKay-Chopin S, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, et al: No causal association identified for human papillomavirus infections in lung cancer. Cancer Res. 74:3525–3534. 2014. View Article : Google Scholar : PubMed/NCBI
8	Simen-Kapeu A, Surcel HM, Koskela P, Pukkala E and Lehtinen M: Lack of association between human papillomavirus type 16 and 18 infections and female lung cancer. Cancer Epidemiol Biomarkers Prev. 19:1879–1881. 2010. View Article : Google Scholar : PubMed/NCBI
9	Hasegawa Y, Ando M, Kubo A, Isa S, Yamamoto S, Tsujino K, Kurata T, Ou SH, Takada M and Kawaguchi T: Human papilloma virus in non-small cell lung cancer in never smokers: A systematic review of the literature. Lung Cancer. 83:8–13. 2014. View Article : Google Scholar : PubMed/NCBI
10	Baba M, Castillo A, Koriyama C, Yanagi M, Matsumoto H, Natsugoe S, Shuyama KY, Khan N, Higashi M, Itoh T, et al: Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas. Oncol Rep. 23:1085–1092. 2010.PubMed/NCBI
11	Tung MC, Wu HH, Cheng YW, Wang L, Chen CY, Yeh SD, Wu TC and Lee H: Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non-small cell lung cancer. Cancer. 119:3367–3376. 2013. View Article : Google Scholar : PubMed/NCBI
12	Kato T, Koriyama C, Khan N, Samukawa T, Yanagi M, Hamada T, Yokomakura N, Otsuka T, Inoue H, Sato M, et al: EGFR mutations and human papillomavirus in lung cancer. Lung Cancer. 78:144–147. 2012. View Article : Google Scholar : PubMed/NCBI
13	Wood DE, Kazerooni E, Baum SL, Dransfield MT, Eapen GA, Ettinger DS, Hou L, Jackman DM, Klippenstein D, Kumar R, et al: Lung cancer screening, version 1.2015: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 13:23–34. 2015.PubMed/NCBI
14	Wei W, Shi Q, Guo F, Zhang BY, Chen C, Zhang NS and Dong XP: The distribution of human papillomavirus in tissues from patients with head and neck squamous cell carcinoma. Oncol Rep. 28:1750–1756. 2012.PubMed/NCBI
15	Zhou Q, Zhang XC, Chen ZH, Yin XL, Yang JJ, Xu CR, Yan HH, Chen HJ, Su J, Zhong WZ, et al: Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer. J Clin Oncol. 29:3316–3321. 2011. View Article : Google Scholar : PubMed/NCBI
16	Syrjänen K: Detection of human papillomavirus in lung cancer: Systematic review and meta-analysis. Anticancer Res. 32:3235–3250. 2012.PubMed/NCBI
17	Ragin C, Obikoya-Malomo M, Kim S, Chen Z, Flores-Obando R, Gibbs D, Koriyama C, Aguayo F, Koshiol J, Caporaso NE, et al: HPV-associated lung cancers: An international pooled analysis. Carcinogenesis. 35:1267–1275. 2014. View Article : Google Scholar : PubMed/NCBI
18	Wang JL, Fang CL, Wang M, Yu MC, Bai KJ, Lu PC and Liu HE: Human papillomavirus infections as a marker to predict overall survival in lung adenocarcinoma. Int J Cancer. 134:65–71. 2014. View Article : Google Scholar : PubMed/NCBI
19	Cheng YW, Chiou HL, Sheu GT, Hsieh LL, Chen JT, Chen CY, Su JM and Lee H: The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women. Cancer Res. 61:2799–2803. 2001.PubMed/NCBI
20	Pallis AG and Syrigos KN: Lung cancer in never smokers: Disease characteristics and risk factors. Crit Rev Oncol Hematol. 88:494–503. 2013. View Article : Google Scholar : PubMed/NCBI
21	Mitsudomi T, Kosaka T and Yatabe Y: Biological and clinical implications of EGFR mutations in lung cancer. Int J Clin Oncol. 11:190–198. 2006. View Article : Google Scholar : PubMed/NCBI
22	Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II, Fong KM, Lee H, Toyooka S, Shimizu N, et al: Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 97:339–346. 2005. View Article : Google Scholar : PubMed/NCBI
23	Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al: EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI
24	Hsu NY, Cheng YW, Chan IP, Ho HC, Chen CY, Hsu CP, Lin MH and Chou MC: Association between expression of human papillomavirus 16/18 E6 oncoprotein and survival in patients with stage I non-small cell lung cancer. Oncol Rep. 21:81–87. 2009.PubMed/NCBI
25	Márquez-Medina D, Gasol-Cudós A, Taberner-Bonastre MT, Samamé Pérez-Vargas JC, Salud-Salvia A and Llombart-Cussac A: Human papillomavirus in non-small-cell lung cancer: The impact of EGFR mutations and the response to erlotinib. Arch Bronconeumol. 49:79–81. 2013.(In English, Spanish). View Article : Google Scholar : PubMed/NCBI
26	Wu HH, Wu JY, Cheng YW, Chen CY, Lee MC, Goan YG and Lee H: cIAP2 upregulated by E6 oncoprotein via epidermal growth factor receptor/phosphatidylinositol 3-kinase/AKT pathway confers resistance to cisplatin in human papillomavirus 16/18-infected lung cancer. Clin Cancer Res. 16:5200–5210. 2010. View Article : Google Scholar : PubMed/NCBI
27	Zhang E, Feng X, Liu F, Zhang P, Liang J and Tang X: Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells. PLoS One. 9:e1034402014. View Article : Google Scholar : PubMed/NCBI
28	Sung WW and Lee H: The role of interleukin-10 in the progression of human papillomavirus-associated lung carcinoma. Oncoimmunology. 2:e258542013. View Article : Google Scholar : PubMed/NCBI