HPV16/18 prevalence in cervical lesions/cancers and p53 genotypes in cervical cancer patients from India.
OBJECTIVE
The HPV16/18 code for an oncoprotein-E6, which binds to p53 tumor suppressor protein and degrades the protein via ubiquitination. A common polymorphism of p53 in exon 4 codon 72, resulting in either proline (Pro) or arginine (Arg), affects HPV16/18 E6-mediated degradation of p53 protein in vivo. Hence, in the current study we investigated the prevalence of HPV16/18 in cervical lesions and the distribution of p53 genotypes in cervical cancers and normal healthy women.


METHODS
DNA from 337 Indian women with invasive cervical cancers, 164 women with clinically normal cervix, 64 women with low-grade squamous intraepithelial lesions (LSIL), and 5 women with high-grade squamous intraepithelial lesions (HSIL) was examined for the presence of HPV16/18 using consensus primers in a polymerase chain reaction (PCR), and the specific HPV type was identified by Southern hybridization of the PCR product using HPV16/18 type-specific nucleotide sequences as probes. Further, 134 women with cervical cancers and 131 healthy women were used to determine the frequency of p53 genotypes, Pro/Pro, Arg/Arg, and Pro/Arg, using peripheral blood cell DNA to indicate the constitutional genotypes and allele-specific primers, in a PCR-based assay.


RESULTS
We observed a prevalence of HPV16/18 in 77% (258/337) of cervical cancer patients, 38% (24/64) of LSILs, 4 of 5 HSILs, and 15.2% (25/164) of normal healthy women. The frequency of distribution of the three genotypes of p53 codon 72 in a subgroup of the HPV16/18-positive cervical cancer patients was Pro/Pro 0.18 and Arg/Arg 0.26, with the heterozygous Pro/Arg 0.56, differing significantly from the genotype frequency in the normal healthy women (chi(2) = 6.928, df = 2, P < 0.05).


CONCLUSIONS
A high prevalence of HPV16/18 was observed in the cervical cancers. The prevalence in LSILs confirms HPV16/18 infection as an early event and further indicates a role in progression of lesions. The p53 genotype distribution indicated that women homozygous for Arg genotype were at a 2.4-fold higher risk for developing HPV16/18-associated cervical carcinomas, compared to those showing heterozygous Pro/Arg genotype (odds ratio 2.4, 95% confidence interval 1.89 to 3.04).
Saranath
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Laboratory of Cancer Genes, Cancer Research Institute, Tata Memorial Centre, Parel, Mumbai, 400 012, India. dsaranath@netscape.net
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D001120:Arginine / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000235:genetics / Q000821:virology; D002584:Cervix Uteri / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India / Q000208:ethnology; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D011392:Proline / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014412:Tumor Virus Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000235:genetics / Q000821:virology; D044465:White People / Q000235:genetics*
D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53; D001120:Arginine; D011392:Proline