Ramón Antaño-Arias

DNMT Enzymes and Their Impact on Cervical Cancer: A State-of-the-Art Review

Genomic DNA methylation is an epigenetic modification that primarily occurs at CpG sites and is associated with the transcriptional repression of genes. This process plays a crucial role in maintaining cellular homeostasis and is catalyzed by a family of enzymes known as DNA methyltransferases (DNMTs), which includes DNMT1, DNMT2, DNMT3A, DNMT3B, and DNMT3L. DNMT1 is classified as a maintenance methyltransferase, whereas DNMT3A and DNMT3B are responsible for de novo methylation. Altered expression of DNMTs has been reported in various human diseases, including cancer. Cancer remains a major global health issue, with an estimated 20 million new cases and 9.7 million deaths reported in 2022. Among women, cervical cancer (CC) ranks fourth in both incidence and mortality worldwide, with persistent infection by high-risk human papillomavirus (HR-HPV) being the primary risk factor. Several studies have demonstrated that DNMT expression and activity are upregulated in CC, suggesting their potential as diagnostic and prognostic biomarkers. HR-HPV infection appears to increase DNMT expression, thereby promoting cervical carcinogenesis through aberrant methylation and subsequent silencing of tumor-suppressor genes such as PTEN, PAX1, and TSLC1. Furthermore, DNMTs are being explored as therapeutic targets in CC. In this review, we summarize the current state of the art regarding DNMTs in cervical cancer and discuss their functional roles and potential utility as diagnostic, prognostic, and therapeutic biomarkers.

Prevalence and Distribution of Human Papillomavirus Genotypes (1997–2019) and Their Association With Cervical Cancer and Precursor Lesions in Women From Southern Mexico

Background Cervical cancer (CC) is the fourth most common malignancy of the female genital tract. Human Papillomavirus (HPV) is the main cause of precancerous lesions and CC cases worldwide Objective We assessed the prevalence and distribution of HPV types and their association with precancerous lesions and CC. Methods HPV genotypes were detected by 3 methods depending on the year of in which the sample was analyzed: MY09/11 RFLPs (1997 to 2010), GP5+/6+ primer systems (2005 to 2010) and INNO-LiPA HPV Genotyping Extra (2010 to 2019) in cervical samples (No-IL: 4445; LSIL: 2464; HSILs: 151 and CC: 253) from women from southern Mexico. Results The overall HPV prevalence was 54.17%, and hpv-16 was the most common genotype. In single infection, the high-risk HPV genotypes (group 1) were associated with squamous intraepitelial lesions (LSIL: HPV–39 (OR = 10.58, 95% CI 4.09–27.36, P < .001); HSIL: HPV-31 (OR = 14.76, 95% CI 6.56–33.20, P < .001); and CC: HPV-16 (OR = 25.01, 95% CI 18.83–33.21, P < .001). In multiple infections, the HPV genotypes (HPV-16 and HPV-18) were also associated with a high risk of lesions [LSIL: HPV-18 (OR = 3.45; 95% CI 1.36–8.91; P = .009); HSIL: HPV-18 (OR = 5.12; 95% CI 1.21–21.68; P = .026); and CC: HPV-16 (OR = 3.03; 95% CI 1.72–5.32; P < .001)] compared to single infection. In the analysis adjusted for age, giving birth, and cigarette smoking, a significant increase in the risk of LSIL, HSIL, and CC was maintained. Conclusions This study provides current data on the prevalence and distribution of HPV genotypes in women from southern Mexico, which could serve as a valuable reference to guide nationwide CC screening programs and provide scientific evidence that could be useful for vaccine development efforts. Likewise, it was identified that infection with carcinogenic HPV genotypes is an independent risk factor for LSIL, HSIL, and CC.