Persistent human papillomavirus infection and cervical neoplasia.
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.
Ferenczy
Alex
A
McGill University and the Sir Mortimer B Davis Jewish General Hospital, Montreal, Québec, Canada. aferen@po-box.mcgill.ca
Franco
Eduardo
E
D001707:Biopsy, Needle; D002170:Canada / Q000453:epidemiology; D002908:Chronic Disease; D005260:Female; D006801:Humans; D015994:Incidence; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology* / Q000821:virology*; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D018570:Risk Assessment; D014412:Tumor Virus Infections / Q000453:epidemiology / Q000473:pathology*; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000821:virology*