Epidemiological evidence and association of human papillomavirus with esophageal cancer in northeastern Thailand: a case–control study

Recently, epidemiological evidence of high-risk human papillomavirus (hrHPV) and its association with the increasing risk of esophageal cancer (EC) have been described. However, the involvement of such a virus in the pathogenesis of EC is still inconclusive in the literature. Therefore, our objective was to clarify the epidemiology of HPV infections in primarily diagnosed EC cases and validate this correlation with hospital-based control patients using a retrospective study with a case–control model. Here, we reported that the overall prevalence of HPV DNA was statistically associated with an increased risk of EC (OR, 3.3; 95% CI, 2.5–4.3). Interestingly, a history of gastroesophageal reflux disease (GERD) was constituted and significantly associated with HPV prevalence (adjusted OR, 4.6; 95% CI, 2.2–9.5). Furthermore, our meta-analysis in public databases also indicated that the combined OR and 95% CI between HPV infection and EC risk were 3.31 and 2.53–4.34, respectively, with significant heterogeneity (I2 = 78%). Variations in the geographic study, tissue type, and detection method remain potential predictors of heterogeneity. In addition, publication bias and sensitivity analysis were not observed, and the results exhibited stable outcomes. Collectively, we specify the recent epidemiological evidence in a validation of the distributed HPV, which might be statistically associated with an increased risk of EC. However, additional high-quality studies with larger sample sizes are needed to further verify the link between HPV and EC

Suppression of miR-22, a tumor suppressor in cervical cancer, by human papillomavirus 16 E6 via a p53/miR-22/HDAC6 pathway.

MicroRNAs (miRNAs) are small non-coding RNAs that function to down-regulate gene expression involving in various cellular processes related to carcinogenesis. Recently, miR-22 was identified as a tumor-suppressing miRNA in many human cancers. However, the regulatory mechanism and the specific function of this miRNA in cervical cancer remain unclear. In the present study, we carried out gene transfection, western blot and quantitative RT-PCR to explore the regulatory mechanism and the functional role of miR-22 in cervical cancer. We verified that miR-22 was down-regulated in cervical cancer tissues and cervical cancer cell lines relative to matched non-tumor tissues and normal human cervical keratinocyte line (HCK1T). By contrast, histone deacetylase 6 (HDAC6) was inversely correlated with miR-22 in both cervical tissues and cancer cell lines. Mechanically, HDAC6 was down-regulated by miR-22 at the post-transcriptional level, via a specific target site within the 3'UTR, identified by a luciferase reporter assay. Moreover, we also showed that the correlation between miR-22 and HDAC6 expression was regulated by an E6/p53 pathway in HCK1Ts expressing HPV16 E6. For functional study, an ectopic expression of miR-22 could inhibit cell proliferation and migration, and could induce apoptosis of cervical cancer cell lines. These findings demonstrated that miR-22 was down-regulated in cervical cancer and inversely collated with its downstream target HDAC6. MiR-22 acts as tumor suppressor by inhibiting proliferation and migration, and by inducing apoptosis of cervical cancer cell lines by targeting the 3'UTR of HDAC6. This newly identified E6/p53/miR-22/HDAC6 regulatory network might be a candidate therapeutic target for cervical cancer