The development of
cervical cancer is preceded by precursor lesions (
cervical intraepithelial neoplasia). Evidence-based epidemiological and molecular data suggest that
persistent infections with human papillomavirus (HPV) types that carry ahigh oncogenic risk are the intermediate endpoints, leading to both intraepithelial and invasive cervical
neoplasia. Integration of highly oncogenic HPVs into host-cell chromosomes is followed by binding of HPV E6 and E7
oncoproteins to tumour-suppressor genes p53 and RB, respectively. This process results in impaired tumour-suppressor-gene function, involving DNA repair, decreased apoptosis, and eventual cell immortalisation. Mutations causing chromosomal alterations, loss of heterozygosity, and proto-oncogene and
telomerase activation in immunopermissive individuals have important roles in virus-induced cervical
carcinogenesis. The so-called non-European variants of HPV 16 and 18 may increase the degradation potential of p53. HPV 16 is polymorphic and, although the evidence is controversial, the
Arg/Arg genotype of p53 could have greater susceptibility to HPV-E6 degradation than the other genotypes. The coincident interplay between the non-European genomic variants of HPV 16/18 and p53
Arg/Arg may explain, at least in part, the persistence of
HPV infection and tumour progression in women with cervical
neoplasia. Further epidemiological and molecular research is needed, to gain insight into HPV-mediated cervical
carcinogenesis. The evidence highlights the need to develop appropriate prophylactic
HPV vaccines and diagnostic and screening tests.