TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies.

BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies. FUNDING: German Research Foundation (DFG).

[Prevalence and cervical human papilloma virus associated factors in patients with rheumatoid arthritis]. / Prevalencia y factores asociados con infección por virus del papiloma humano cervical en pacientes con artritis reumatoide.

BACKGROUND: Nevertheless its association with cervicouterine cancer, there is no information about cervical human papillomavirus infection prevalence in patients with rheumatoid arthritis. OBJECTIVE: To evaluate human papillomavirus infection prevalence through molecular biology tests, and to analyze this infection related factors in patients with rheumatoid arthritis. MATERIAL AND METHOD: Analytic, transversal study to 250 patients: 61 women with rheumatoid arthritis selected from a rheumatologic external consult of a second level hospital, and 189 healthy women, with cervical cytology, of a first level hospital. They were polled to find infection risk factors. They were exfoliated to get cervix cells to extract its DNA and detect human papillomavirus (chain reaction of polymerase with specific consensus markers), and identification of restriction enzyme in high and low risks viruses. Prevalence was calculated, and adjusted factors analysis was performed through logistic regression with odds ratio and confidence intervals of 95%. RESULTS: Prevalence of papillomavirus infection in patients with rheumatoid arthritis was 30%, and in control group was 24%, with an odds ratio of 0.8 (CI 95% 0.42-1.6, p = 0.5). Ninety-four percent of the most frequent viral types in women with rheumatoid arthritis were high risk (mainly types 16, 58, and 18). Factors associated with higher human papillomavirus adjusted to rheumatoid arthritis were: more than one sexual partner (OR = 5.8 CI 95% 1.1-31.1, p = 0.04), more than one sexual intercourse weekly (OR = 6.7, CI 95% 0.9-51.6, p = 0.06), circumcised sexual partner (OR = 9.0, CI 95% 1.2-64.4, p = 0.02). Patients and controls had same values of marital status. Seventy-four percent of controls worked, compared to 44% of women with rheumatoid arthritis (p < 0.01). CONCLUSION: One out of three women with rheumatoid arthritis has human papillomavirus infection and 94% has the high-risk viral type. Infection associated factors mainly includes sexual partner ones; due to high risk of cervical dysplasia, it is necessary the early detection of the infection and surveillance.

P16INK4a immunohistochemistry improves the reproducibility of the histological diagnosis of cervical intraepithelial neoplasia in cone biopsies.

OBJECTIVE: Cervical cancer is currently the most frequently occurring cancer among women in Mexico. Mexican cervical cancer prevention programs have been unsatisfactory in part because the tests used to diagnose precursor lesions have poor reproducibility. The implementation of specific biomarkers may overcome these limitations. Here, we analyzed whether immunohistochemistry for p16(INK4a) could improve the reproducibility of histopathological diagnoses of cervical precancerous lesions. METHODS: Serial sections of 78 specimens were stained for H&E and p16(INK4a) and independently interpreted by three Mexican pathologists. Specimens were interpreted and categorized in two ways: 1) four diagnostic categories including negative lesions, CIN1, CIN2, and CIN3, or 2) two diagnostic categories; either lesions that do not require therapy (negative, CIN1), or lesions that require therapy (>or=CIN2). The agreement in diagnoses between pairs of observers was evaluated by kappa statistics. RESULTS: The best concordance in diagnosing was observed with two categories and p16(INK4a) staining. Interestingly, the overall diagnostic discordances of higher than one CIN grade were 26.1% for H&E and 9.20% for p16(INK4a) (P<0.001). Using four diagnostic categories, weighted kappa values for each pair of observers were 0.28, 0.15, and 0.36 for H&E and 0.34, 0.35, and 0.60 for p16(INK4a) stains. Using two diagnostic categories, kappa values were 0.36, 0.12, and 0.18 for H&E and 0.59, 0.70, and 0.59, p16(INK4a) stains. CONCLUSION: These data show that p16(INK4a) immunohistochemistry substantially improved the reproducibility of interpreting histological slides. This approach may result in more accurate diagnoses and improved clinical management of patients with cervical precancerous lesions in Mexico and elsewhere.