Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

hnRNP K induces HPV16 oncogene expression and promotes cervical cancerization.

PURPOSE: This study aims to explore the expression of hnRNP K in cervical carcinogenesis and to investigate the regulatory role of hnRNP K on HPV16 oncogene expression as well as biological changes in cervical cancer cells. METHODS: In total 1042 subjects, including 573 with the normal cervix and 469 with different grades of cervical lesions were enrolled in this study to explore the association between hnRNP K and HPV16 oncogene expression in cervical carcinogenesis. Additionally, the Gene Omnibus (GEO) database was used to analyze hnRNP K mRNA expression in cervical cancerization. Meanwhile, the effects of hnRNP K on cell biological functions and HPV16 oncogene expression were investigated in Siha cells. Moreover, Function analyses were conducted using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases after ChIP-seq. RESULTS: hnRNP K was highly expressed in cervical cancer and precancerous lesions, and positively correlated with HPV16 E6, but negatively correlated with HPV16 E2 and HPV16 E2/E6 ratio. hnRNP K induced cell proliferation, inhibited apoptosis and caused cell cycle arrest in the S phase, and particularly increased HPV16 E6 protein expression. CONCLUSION: This study revealed that hnRNP K overexpression has important warning significance for the malignant transformation of cervical lesions, and could be used as a potential therapeutic target for inhibiting the carcinogenicity of HPV16 and prevention of cervical carcinogenesis.