Fabio Russomano

Factors associated with increased prevalence of human papillomavirus infection in a cohort of HIV-infected Brazilian women

OBJECTIVES Human papillomavirus (HPV) infection is a major risk factor for cervical disease. Using baseline data from the HIV-infected cohort of Evandro Chagas Clinical Research Institute at Fiocruz, Rio de Janeiro, Brazil, factors associated with an increased prevalence of HPV were assessed. METHODS Samples from 634 HIV-infected women were tested for the presence of HPV infection using hybrid capture II and polymerase chain reaction. Prevalence ratios (PR) were estimated using Poisson regression analysis with robust variance. RESULTS The overall prevalence of HPV infection was 48%, of which 94% were infected with a high-risk HPV. In multivariate analysis, factors independently associated with infection with high-risk HPV type were: younger age (<30 years of age; PR 1.5, 95% confidence interval (CI) 1.1-2.1), current or prior drug use (PR 1.3, 95% CI 1.0-1.6), self-reported history of HPV infection (PR 1.2, 95% CI 0.96-1.6), condom use in the last sexual intercourse (PR 1.3, 95% CI 1.1-1.7), and nadir CD4+ T-cell count <100cells/mm(3) (PR 1.6, 95% CI 1.2-2.1). CONCLUSIONS The estimated prevalence of high-risk HPV-infection among HIV-infected women from Rio de Janeiro, Brazil, was high. Close monitoring of HPV-related effects is warranted in all HIV-infected women, in particular those of younger age and advanced immunosuppression.

Immune factors involved in the cervical immune response in the HIV/HPV co-infection.

Aims: Immune factors influencing the progression of cervical intraepithelial neoplasia (CIN) to cancer remain poorly defined. This study investigates the expression of RANTES, MIP1α, COX1, COX2, STAT3, TGFβRI, IL10R, TNFαRII and TLR4 in the cervical immune response in HIV/HPV (human papillomavirus) co-infected women. Methods: Cervical biopsies of 36 patients were assayed by immunohistochemistry, and the Ventana Benchmark System was used for HIV-nef detection. Results: Cervices from HIV-positive patients exhibited nef in cells mainly around blood vessels, and showed a decreased expression of all the immune factors tested except IL10R and STAT3, while RANTES (5.54 cells/mm2) was highly expressed in comparison with controls (1.41 cells/mm2, p = 0.028). COX1 was decreased in the HIV/HPV- (0.32 cells/mm2, p = 0.017) and HPV-infected patients (0.21 cells/mm2, p = 0.015) compared with controls (3.28 cells/mm2). Conclusions: It is suggested that RANTES in HIV/HPV co-infection may influence the development of CIN leading to progression to cervical cancer.

Assessing sexually transmitted infections in a cohort of women living with HIV/AIDS, in Rio de Janeiro, Brazil

A cohort of 458 HIV-positive women under antiretroviral therapy has been followed at a reference hospital in Rio de Janeiro, Brazil. Most of them belong to impoverished social strata. Patients were screened for sexually transmitted infections (STIs) and gynaecologic conditions. Some STIs were found to be uncommon (e.g. chlamydial and gonococcal infections), while some conditions (bacterial vaginosis) and STIs, e.g. hepatitis B and human papilloma virus (HPV) infection, were found to be quite prevalent. The latter is of special concern, due to the high prevalence of HIV/HPV co-infection (∼51%) and its association with severe immunodeficiency, in a context of unacceptable high levels of uterine cancer and uneven gynaecological care. HIV-positive women are in need of comprehensive health services, including high-quality, regular, gynaecologic care in order to diagnose and treat lower genital tract infections and prevent the evolution of HPV-related lesions. Reproductive counselling should be a part of this approach.

Pre-invasive cervical disease and uterine cervical cancer in Brazilian adolescents: prevalence and related factors

The objective was to describe the prevalence and factors associated with uterine cervical cancer (CA) and high-grade squamous intraepithelial lesions (HSIL) in adolescents. A cross-sectional study was carried out with 702 sexually active adolescents treated at a general hospital in Rio de Janeiro, Brazil, from 1993 to 2002. Screening was performed by cytopathology and colposcopy and confirmation by biopsy. Exposure variables were socio-demographic characteristics and those related to reproductive health, habits, and sexual behavior. Adjusted odds ratios were estimated using multivariate logistic regression analysis. Based on histopathology, the prevalence of HSIL/CA was 3% (95%CI: 1.8-4.6). There was one case of invasive cancer. With each additional pregnancy, the odds of HSIL/CA increased by 2.2 (95%CI: 1.1-4.4). Age was also associated with this outcome, doubling the odds of acquiring this degree of disease with each year of age (OR = 2.0; 95%CI: 1.2-3.4). The prevalence of lesions suggests the importance of including sexually active adolescent females in cervical cancer screening programs aimed at early detection and treatment of these lesions.

Factors associated with colposcopy-histopathology confirmed cervical intraepithelial neoplasia among HIV-infected women from Rio De Janeiro Brazil.

Introduction Despite the availability of preventive strategies (screening tests and vaccines), cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV) and thus development of cervical squamous intraepithelial neoplasia (CIN). Methods Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ). At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+ diagnosis. Results The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28–41 years). The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+ was 6.0%. Factors associated with CIN2+ diagnosis in the multivariate model were age < years compared to ≥35 years (aPR  =  3.22 95%CI 1.23–8.39), current tobacco use (aPR  =  3.69 95%CI 1.54–8.78), nadir CD4 T-cell count <350 cells/mm3 when compared to ≥ 350 cells/mm3 (aPR  =  6.03 95%CI 1.50–24.3) and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR  =  2.68 95%CI 0.99–7.24). Discussion Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical cancer mortality in this group of women.

Immunohistochemical expression of cyclin D1, p16Ink4a, p21WAF1, and Ki-67 correlates with the severity of cervical neoplasia.

High-risk human papillomaviruses are closely associated with cervical cancer and its precursor lesions through interactions between the E6 and E7 oncoproteins and the cell-cycle regulatory proteins, such as p53 and pRb, respectively. As other molecules involved in the cell-cycle control seem to be important for human papillomavirus (HPV)-mediated cervical carcinogenesis, we have analyzed the expression of p53, p21, p16, cyclin D1, and Ki-67 and the presence of HPV (HPV pool and HPV-16) by immunohistochemical studies using tissue microarray in low squamous intraepithelial lesions (n=50), high squamous intraepithelial lesions (n=98), and cervical carcinoma (n=18). We have found a significant increase in the expression of p16 and p21 (P<0.001) from low- to high-grade lesions and cancer. In contrast, cyclin D1 expression showed a significant decrease in more severe lesions (P<0.001). p16, Ki-67, p21, and p53 positivity increased with the cell-layer level and the lesion severity, with stronger correlations being observed for p16 and Ki-67. High positivity for HPV pool (96.3%) and HPV-16 (77.5%) immunostaining was detected in all cases, with an association between p16 and cyclin D1 expression and HPV-16 infection. Our tissue microarray results corroborate the usefulness of the immunohistochemical assessment of cell-cycle biomarkers in distinguishing different groups of precursor lesions of the cervix and cervical carcinoma.

Recurrence of cervical intraepithelial neoplasia grades 2 or 3 in HIV-infected women treated by large loop excision of the transformation zone (LLETZ)

CONTEXT AND OBJECTIVE Women infected by HIV are more likely to have cervical cancer and its precursors. Treatment of the precursor lesions can prevent this neoplasia. The aim of this study was to assess the likelihood of recurrent cervical intraepithelial neoplasia grades 2 or 3 (CIN 2-3) in HIV-infected women, compared with HIV-negative women, all treated by large loop excision of the transformation zone (LLETZ). DESIGN AND SETTING A cohort study in Instituto Fernandes Figueira, Fundação Oswaldo Cruz (IFF-Fiocruz), Rio de Janeiro. METHOD 55 HIV-positive and 212 HIV-negative women were followed up after LLETZ for CIN 2-3 (range: 6-133 months). RESULTS The incidence of recurrent CIN 2-3 was 30.06/10,000 woman-months in the HIV-positive group and 4.88/10,000 woman-months in the HIV-negative group (relative risk, RR = 6.16; 95% confidence interval, CI: 2.07-18.34). The likelihood of recurrence reached 26% at the 62nd month of follow-up among the HIV-positive women, and remained stable at almost 0.6% at the 93rd month of follow-up among the HIV-negative women. We were unable to demonstrate other prognostic factors relating to CIN recurrence, but the use of highly active antiretroviral therapy (HAART) may decrease the risk of this occurrence among HIV patients. CONCLUSION After LLETZ there is a higher risk of recurrence of CIN 2-3 among HIV-positive women than among HIV-negative women. This higher risk was not influenced by margin status or grade of cervical disease treated. The use of HAART may decrease the risk of this occurrence in HIV patients.

Prognosis of Intraepithelial Cervical Lesion during Adolescence in Up to Two Years of Follow-Up

Our objective was to describe the evolution of cervical SIL within 24 months of the initial diagnosis, in a cohort study of 147 sexually active adolescents attending a public health service in Rio de Janeiro, between 1993 and 2006. The participants were divided in two groups, according to whether cervical biopsy was performed or not. The median of the interval between sexual debut and the atypical cytopathology was 12 months and in 8.2% of patients there was a diagnosis of HSIL at the first abnormal smear. After a two-year follow-up by cytology, the regression (ASCUS 91%, LSIL 63.6%, HSIL 50%) and progression (LSIL 6.1%) were verified. In the group undergoing biopsy, the final histological regression reached 59.4% for CIN1 and 71.4% for CIN2, while the progression from CIN1 to CIN 2/3 was 3.1%. Our results corroborate the recommendation for conservative management in compliant adolescents due to a high regression rate. However, there should be maintained a careful follow-up based on the possible evolution of the lesion.

Cervical cytological abnormalities and factors associated with high-grade squamous intraepithelial lesions among HIV-infected women from Rio de Janeiro, Brazil:

Although cervical cancer remains a major public health problem in Brazil, knowledge of cervical cytological abnormalities among HIV-infected women remains scarce. At baseline evaluation of a cohort followed in Rio de Janeiro, Brazil, 703 HIV-infected women underwent cytology-based cervical cancer screening and human papillomavirus (HPV) DNA testing. Poisson regression analysis was used to evaluate the association of factors with the presence of high-grade squamous intraepithelial lesions (HSIL). Cervical cytology was abnormal in 24.3% of the women; 4.1% had HSIL. Beyond HPV infection, factors independently associated with the presence of HSIL was age (≥25 and ≤40 years, prevalence ratio [PR] 2.60, 95% confidence interval [CI] 1.11–6.10), and more than three pregnancies was protective (PR 0.33, 95% CI 0.11–0.94). High coverage of cervical cancer screening is warranted to prevent morbidity and mortality from cervical cancer in this population.

Cervical stenosis following electrosurgical conization

CONTEXT AND OBJECTIVE Cervical stenosis is a postoperative complication of procedures for treating preinvasive lesions of the cervix and takes on particular importance due to the clinical repercussions associated with it. Furthermore, it causes limitations in relation to cytological and colposcopic follow-up. The aim here was to assess the incidence of cervical stenosis among a cohort of patients who underwent electrosurgical conization and to identify possible prognostic factors associated with its occurrence. DESIGN AND SETTING Retrospective study at Gynecology and Obstetrics Department, Instituto Fernandes Figueira, Rio de Janeiro. METHODS This was an observational study among a cohort of patients who underwent electrosurgical conization of the uterine cervix. The possible predictive variables were analyzed as bivariate means between the groups with and without stenosis. We also calculated the incidence density rate ratio for cervical stenosis in relation to each possible predictive variable and the respective confidence intervals (95%). Levels of 5% were considered significant. RESULTS 274 patients who underwent electrosurgical conization of the uterine cervix with a minimum follow-up period of six months were included. The crude incidence of cervical stenosis was 7.66% and the incidence density was 3.3/1,000 patients-month. CONCLUSIONS We did not find associations between the variables for stenosis. However, we observed borderline significance levels relating to hemorrhagic complications before and after the operation (p = 0.089).