IMPACT OF P21 SER31ARG AND TP53 ARG72PRO POLYMORPHISMS ON HPV SUSCEPTIBILITY AND CERVICAL LESION SEVERITY

Abstract

Introduction: Although preventable and treatable, Uterine Cervical Cancer (UCC) continues to claim lives every year. Even though Human Papillomavirus (HPV) is the main etiological agent of this disease, single nucleotide polymorphisms (SNPs) in genes involved in cell cycle control, such as P21 and TP53, are important factors in cancer development. Objective: This retrospective case-control study aimed to investigate the association of the P21 Ser31Arg (rs1801270) and TP53 Arg72Pro (rs1042522) polymorphisms with HPV infection persistence and with the progression of Cervical Intraepithelial Neoplasia (CIN I) to High-Grade Squamous Intraepithelial Lesions (HSIL) to UCC. Methods: We analyzed 581 women, including 282 cases (HPV ^positive, with CIN/ UCC) and 299 controls (HPV ^negative, without CIN). Samples from the case group were obtained from paraffin- embedded histological tissues, while control samples were collected from vaginal secretions immersed in saline solution. The rs1801270 SNP was evaluated using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), and the rs1042522 SNP was analyzed using the Mismatch Amplification Mutation Assay-PCR (MAMA-PCR). Results: The P21 rs1801270 polymorphism was significantly associated with increased risk of HPV persistence and CIN. Individuals with CA (OR = 2.23; 95% CI: 1.366–3.650; p < 0.0001) and AA (OR = 3.87; 95% CI: 2.455–6.113; p < 0.0001) genotypes showed increased CIN/UCC risk. Although no link with HSIL was found individually, CA+AA (OR = 3.14; 95% CI: 2.04–4.83; p = 7.57×10⁻⁸) suggests A allele triples risk. TP53 rs1042522 was associated with HPV: GC (OR = 2.45; 95% CI: 1.632–3.682; p < 0.0001), CC (OR = 1.74; 95% CI: 1.168–2.597; p < 0.0001), but CC was protective against HSIL (OR = 0.049; 95% CI: 0.023–0.103; p < 0.0001). GC+CC vs GG confirmed C allele increases HPV risk (OR = 2.06; 95% CI: 1.48–2.87; p = 2.17×10⁻⁵), yet may protect against HSIL. Conclusion: our results indicate that the P21 rs1801270 and TP53 rs1042522 polymorphisms are associated with persistent HPV infection and NIC I. The P21 A allele increased CIN risk, while the TP53 C allele was linked to HPV susceptibility; the CC genotype showed a protective effect against HSIL. These results highlight the relevance of genetic polymorphisms as molecular markers capable of fostering more accurate risk stratification and guiding clinical practices.