HPV16/18 prevalence in cervical lesions/cancers and p53 genotypes in cervical cancer patients from India

Gynecol Oncol. 2002 Aug;86(2):157-62. doi: 10.1006/gyno.2002.6735.

Abstract

Objectives: 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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / metabolism
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / virology
  • Cervix Uteri / virology*
  • DNA, Viral / analysis
  • Disease Progression
  • European Continental Ancestry Group / genetics*
  • Female
  • Genotype
  • Humans
  • India / ethnology
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / virology
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Prevalence
  • Proline / metabolism
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Virus Infections / complications*
  • Tumor Virus Infections / epidemiology
  • Tumor Virus Infections / virology
  • Uterine Cervical Neoplasms / etiology*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / virology

Substances

  • DNA, Viral
  • Tumor Suppressor Protein p53
  • Arginine
  • Proline