Human papillomavirus infection as a prognostic marker for lung adenocarcinoma: a systematic review and meta-analysis

Abstract

Although a number of studies have investigated the association between human papillomavirus (HPV) and lung cancer prognosis, the results remain inconsistent. We therefore conducted a meta-analysis of epidemiologic studies to address this issue. Searches of the MEDLINE and EMBASE electronic databases from their inception until June 30, 2016 yielded nine studies involving a total of 1,205 lung cancer cases that were used to conduct the meta-analysis. Study-specific risk estimates were pooled using a random-effects model. The pooled hazard ratio (HR) comparing HPV-positive to HPV-negative cancers 1.00 (95% confidence interval (CI): 0.78-1.28) was not significantly correlated with overall survival. However, lung adenocarcinoma patients with HPV infections exhibited a survival benefit compared to those without HPV infection (HR=0.69, 95% CI: 0.50-0.96). This meta-analysis suggests HPV infection is a prognostic marker in lung adenocarcinoma. To further elucidate the epidemiology and pathogenesis of HPV infections in lung cancer, future large prospective studies are encouraged to stratify survival analysis based on the pathological type and clinical stage of the cancer.

Human papillomavirus is not associated to non-small cell lung cancer: data from a prospective cross-sectional study

“…Together, these data indicate a wide rate of variation in the frequency of HPV among lung cancers with the highest frequency of virus being reported in East Asian countries, with a prevalence variation of 11.8-55.0% [16]. Finally, in a recent meta-analysis [40], 46 studies that demonstrated a higher prevalence of HPV in Asian countries (28.1%) when compared with European countries (8.4%) and countries from North and South America (21.3%), with regional differences between countries being observed. When the analysis was limited to HPV-16 and 18, which are the HPV types of higher oncogenic risk, a significant higher prevalence was observed in Asia (23.1%) in relation to Europe (4.4%) or the Americas (15.6%).…”

“…The few p16-positive cases are therefore unrelated to HPV. Several reports evaluating the prevalence of HPV DNA are increasing and new evidences with the HPV infection and NSCL coexistence are emerging [40][41][42][43]. However, there is still a lack of robust evidences of the possible participation of HPV in NSCLC carcinogenesis [44].…”

“…This is interesting because some studies suggest that the heterogeneity in the prevalence of HPV in lung cancer is mainly due to the geographic differences, the different histological types analysed and the different detection methods used [19], besides the sample size, demographic composition of each study and host-specific factors [14,16]. There is a consensus among most of the studies that it is necessary to investigate more cases to understand the real role (if any) of HPV in pulmonary carcinogenesis [14,16,20,37,40]. Still in an attempt to explore the relationship of HPV with NSCLC, IHC was performed in NSCLC paraffin samples to evaluate the expression of p16, a protein considered an indirect marker for HPV infection, since in SCC and adenocarcinoma of uterine cervix and, in a fraction of oropharyngeal squamous cell carcinomas, the overexpression of p16 is strongly related to HPV infection [37].…”

Human papillomavirus infection maybe not associated with primary lung cancer in the Fujian population of China

“…A previous meta‐analysis showed that platelet elevation promotes blood metastasis in cancer cells and is associated with a poor prognosis in lung cancer . However, the overall survival rate of patients with HPV‐positive lung cancer was not significantly different from that of HPV‐negative patients . The relationship between HPV infection, platelet elevation, and prognosis of lung cancer still needs further exploration.…”

“…29 However, the overall survival rate of patients with HPV-positive lung cancer was not significantly different from that of HPV-negative patients. 30 The relationship between HPV infection, platelet elevation, and prognosis of lung cancer still needs further exploration.…”