Synchronicity of P53 Mutation and Multiple High-Risk HPV Genotypes, and the Risk of Cervical Cancer among Women in Osogbo, Nigeria

BackgroundIn low-and middle-income countries, high burden of cervical cancer is associated with human papillomavirus (HPV) due to poor screening and diagnostic methods at early stage. Reports showed that there are discrepancies in data correlating HPV-infection with development of cervical cancer while the functional roles of P53 oncogenic mutation are controversial. Furthermore, the molecular pathogenesis of multiple HPV-genotypes remains an open question. Thus, advancing investigations on HPV-associated cervical abnormalities would add to early diagnostic precision. MethodsTwo hundred (n=200) cervical samples were collected from apparently healthy, active adult women following an ethical approval. Laboratory analyses were conducted through cytological assessment and histochemistry screening using the Papanicolaou smear. PCR methods were used to characterize HPV-DNA genotypes and P53 gene mutations. Positive cervical dysplasia cases were matched with HPV-DNA, and the HPV-genotypes were used to evaluate the prevalence of various HPV-subtypes and the risk of cervical cancer. ResultsTwenty-six (n=26) cervical dysplasia and fifty-one (n=51) HPV+ were identified comprising single and multiple genotypes. While nine cases (n=9) showed p53 gene mutation with concurrent multiple high-risk HPV (hrHPV) genotypes, none of the single hrHPV genotypes had p53 mutation. More so, individuals with coexisting p53 mutation and multiple hrHPV-genotypes already manifesting cervical dysplasia were 22.2% of the group, while 77.8% had normal cervical architecture, the fate of whom was unknown during investigation. There was a higher cervical dysplasia among those with HPV oncogenes; there were connections between the HPV positivity with some genotypes (hrHPV16,18,31 and 33, respectively) and p53 mutation. ConclusionP53 gene mutation was independent of HPV-associated cervical abnormalities in single hrHPV-genotype, though other mechanistic drivers attributed to p53 dysfunction by E6 and E7 remain plausible. On the other hand, infection with multiple hrHPVs showed a concomitant predominance with the P53 mutation, implying a potential interplay and an increased risk of cervical cancer.