The number of non-small-cell lung cancer (NSCLC) patients reported as infected with human papillomavirus (HPV) varies among countries and by race and geographical location. Furthermore, the relationship between HPV and the expressions of p53 and p16 remains unclear. A large cohort of NSCLC patients from Shanghai was studied. Paraffin sections from 128 cases of lung adenocarcinoma (ADC) and 134 cases of squamous cell carcinoma (SQC) were collected from the Shanghai Chest Hospital. Samples were analyzed by polymerase chain reaction (PCR) and reverse dot blot for detection of HPV DNA and by immunohistochemistry for detection of p53 and p16 expressions. The rate of HPV infection in SQC cases was significantly higher than in ADC cases (12.69 versus 3.91 %). Females with SQC had a significantly higher rate of HPV infection compared to males with SQC (18.75 versus 7.14 %, p = 0.044). HPV infection was correlated with gender and age in SQC but not with the degree of tumor differentiation, TNM stage, or smoking. Koilocytosis was significantly correlated to the tumor differentiation grade, regardless of age and TNM stage. The expressions of p53 and p16 were correlated with HPV infection and the tumor histological type but not with the degree of tumor differentiation, TNM stage, smoking, gender, or age. p53-positive expression was significantly higher in HPV-infected SQC cases than in those not infected with HPV. There was no statistically significant difference in the expression of p16 between the two groups. Data showed that HPV infection may be an important virulence factor in SQC, particularly in female patients. HPV infection appears to be involved in cancer progression in SQC by promoting the expression of p53; however, p16 cannot be used as a surrogate marker for HPV infection in SQC.
Squamous cell carcinoma (SQC) Human papillomavirus (HPV) p53 p16
This is a preview of subscription content, log in to check access.
This work was supported by the Shanghai R&D public service platform project “common malignant tumor biobank (Network) construction” (2012).
Zhang YW, Jin B, Shao MH, Dong Y, Lou YQ, Huang AM, et al. Monitoring of carcinoembryonic antigen levels is predictive of EGFR mutations and efficacy of EGFR-TKI in patients with lung adenocarcinoma. Tumour Biol. 2014;35(5):4921–8.CrossRefPubMedGoogle Scholar
Zhai K, Ding J, Shi H. HPV and lung cancer risk: a meta-analysis. J Clin Virol. 2014;09(014).Google Scholar
Fei Y, Yang J, Hsieh WC, Wu JY, Wu TC, Goan YG, et al. Different human papillomavirus 16/18 infection in Chinese non-small cell lung cancer patients living in Wuhan. China Jpn J Clin Oncol. 2006;36(5):274–9.CrossRefPubMedGoogle Scholar
Yanagawa N, Wang A, Kohler D, Santos GC, Sykes J, Xu J, et al. Human papilloma virus genome is rare in North American non-small cell lung carcinoma patients. Lung Cancer. 2013;79:215–20.CrossRefPubMedGoogle Scholar
Doxtader EE, Katzenstein AL. The relationship between p16 expression and high-risk human papillomavirus infection in squamous cell carcinoma from sites other than uterine cervix: a study of 137 cases. Hum Pathol. 2012;43:327–32.CrossRefPubMedGoogle Scholar
Wu JB, Li XJ, Zhu W, Liu XP. Detection and pathological value of papillomavirus DNA and p16INK4A and p53 protein expression in cervical intraepithelial neoplasia. Oncol Lett. 2014;7:738–44.PubMedPubMedCentralGoogle Scholar
Shamanin V, Delius H, Villiers EM. Development of a broad spectrum PCR assay for papillomaviruses and its application in screening lung cancer biopsies. J Gen Virol. 1994;75:1149–56.CrossRefPubMedGoogle Scholar
Teng HH, Li XJ, Liu XP, Wu J, Zhang J. The absence of human papillomavirus in esophageal squamous cell carcinoma in East China. Int J Clin Exp Pathol. 2014;7(7):4184–93.PubMedPubMedCentralGoogle Scholar
Sarchianaki E, Derdas SP, Ntaoukakis M, Vakonaki E, Lagoudaki ED, Lasithiotaki I, et al. Detection and genotype analysis of human papillomavirus in non-small cell lung cancer patients. Tumour Biol. 2014;35(4):3203–9.CrossRefPubMedGoogle Scholar
Welt A, Hummel M, Niedobitek G, Stein H. Human papillomavirus infection is not associated with bronchial carcinoma: evaluation by in situ hybridization and the polymerase reaction. J Pathol. 1997;181:276–80.CrossRefPubMedGoogle Scholar
Klein F, Waleed FM, Amin K, Petersen I. Incidence of human papillomavirus in lung cancer. Lung Cancer. 2009;65:13–8.CrossRefPubMedGoogle Scholar
Aguayo F, Castillo A, Koriyama C, Higashi M, Itoh T, Capetillo M, et al. Huamn papillomavirus-16 is integrated in lung carcinomas: a study in Chile. Br J Cancer. 2007;97(1):85–91.CrossRefPubMedPubMedCentralGoogle Scholar
Chen YW, Chiou HL, Chen JT, Chou MC, Lin TS, Lai WW, et al. Gender difference in human papillomavirus infection for non-small cell lung cancer in Taiwan. Lung Cancer. 2004;46:165–70.CrossRefPubMedGoogle Scholar
Wang J, Chang YW, Wu DW, Chen JT, Chen CY, Chou MC, et al. Frequent fhit gene los of heterozygosity in human papillomavirus-infected nonsmoking female lung cancer in Taiwan. Cancer Lett. 2006;235:18–25.CrossRefPubMedGoogle Scholar
Fei M, Li J, Du J, You J, Zhang S, He W, et al. Distribution human papillomavirus 16 and 18 among high-risk women to cervical cancer. Zhonghua Liu Xing Bing Xue Za Zhi. 2014;35(5):514–8.PubMedGoogle Scholar
Hennig EM, Suo Z, Karlsen F, Holm R, Thoresen S, Nesland JM. HPV positive bronchopulmonary carcinomas in women with previous high-grade cervical intraepithelial neoplasis (CINIII). Acta Oncol. 1999;38:639–47.CrossRefPubMedGoogle Scholar
Katiyar S, Hedau S, Jain N, Kar P, Khuroo MS, Mohanta J, et al. P53 gene mutation and human papillomavirus (HPV) infection in esophaged carcinoma from three different endemic geographic regions of India. Cancer Lett. 2005;218:69–79.CrossRefPubMedGoogle Scholar
Hsu NY, Cheng YW, Chan IP, Ho HC, Chen CY, Hsu CP, et al. Association between expression of human papillomavirus 16/18 E6 oncoprotein and survival in patients with stage I non-small cell lung cancer. Oncol Rep. 2009;21(1):81–7.PubMedGoogle Scholar
Reimers N, Kasper HU, Weissenborn SU, Stutzer H, Preuss SF, Hoffmann TK, et al. Combined analysis of HPV-DNA, p16 and EGFR expression to precict prognosis in oropharyngeal cancer. Int J Cancer. 2007;120:1731–8.CrossRefPubMedGoogle Scholar