Andrea Alves Ribeiro

A portrait of single and multiple HPV type infections in Brazilian women of different age strata with squamous or glandular cervical lesions

BackgroundCervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Our objective was to assess the relationships between single- (ST) and multiple-type (MT) HPV infections with patients’ age and lesion pathological status.Methods328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across histological types and age strata.Results287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59.ConclusionsOur data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18.

Association between HPV types and species groups and cervical neoplasia from a high-risk area for cervical cancer, Goiânia, Brazil.

This study was designed to evaluate the effect of single or multiple-human papillomavirus (HPV) infection and phylogenetic groups on the prevalence and severity of cervical intraepithelial neoplasia (CIN) in women undergoing colposcopy after an abnormal cervical smear. Colposcopy was performed in 198 cases and biopsy was performed in 193 patients. All specimens were tested for 27 HPV genotypes using the Roche polymerase chain reaction reverse line blot assay. The overall prevalence of HPV infection in women with an abnormal cervical smear was 86% (171 of 198). The prevalence of HPV 16 in high-grade CIN (2/3) was 52% (40 of 76), being detected in 88.8% of cases (8 of 9) of invasive carcinoma. The prevalence of HPV types 31 and 35 in high-grade CIN was 10.5% (8 of 76) and 6.6% (5 of 76), respectively. Single or multiple-type infection involving HPV 16 were significantly associated with a diagnosis of high-grade neoplasia (≥CIN 2) [odds ratio (OR) 6.49; 95% confidence interval (CI): 1.88-23.44 and OR: 3.65; 95% CI: 1.13-12.15] even after adjustment for HPV-DNA. A statistically significant association was also found between HPV 16 and the other HPV types belonging to species &agr; 9 and a diagnosis of high-grade neoplasia (OR: 7.62; 95% CI: 1.28-51.58); however, no association was found between HPV 16 and the other HPV types belonging to species &agr; 7. HPV 16 is the most important predictor of high-grade cervical neoplasia. Multiple-type infections are predictors of high-grade cervical neoplasia when type 16 is present.

Association between the human papillomavirus, bacterial vaginosis and cervicitis and the detection of abnormalities in cervical smears from teenage girls and young women

Human papillomavirus (HPV) infection, bacterial vaginosis (BV), and cervicitis may play a role in the presence of cytological abnormalities in female adolescents and young women. This study aimed to estimate the prevalence of HPV, BV and cervicitis in female adolescents and young women and evaluate whether these conditions are associated with a finding of cytological abnormalities in cervical smears.

Cytopathic effects of human papillomavirus infection and the severity of cervical intraepithelial neoplasia : A frequency study

Cytopathic effects related to the human papillomavirus (HPV) infection are more frequently found in cervical intraepithelial neoplasia (CIN) 1; however, there are indications that at least half the histological diagnoses of CIN2 and CIN3 include koilocytosis areas. The objective of this study was to evaluate the frequency of the cytological criteria suggestive of HPV infection in the cervical smears of women with a histological diagnosis of CIN. One hundred and sixty‐two women with abnormal cervical smears and a diagnosis of CIN confirmed by histopathology were selected, including 46 cases of CIN 1, 42 of CIN 2 and 74 cases of CIN 3. Koilocytosis was found in 63% of the smears from women with a histopathological diagnosis of CIN 1. This sign was observed in 26.2% and 25.7% of smears of women with a diagnosis of CIN 2 and CIN 3, respectively. Cytomegaly also was frequent in cervical smears of women with histopathological diagnosis of CIN 1 (71.8%). On the other hand, spindle cells and atypical metaplasia were more frequent in women with CIN 2 and CIN 3. Atypical parakeratosis showed similar frequency in all grades of CIN diagnosis. Koilocytois and cytomegaly were inversely correlated with the diagnosis of CIN2 or CIN 3, with OR values respectively of 0.30 (95%CI 0.13–0.68) and 0.26 (95%CI 0.11–0.58). The others signs analyzed did not show any significant association. Koilocitosis and cytomegaly can provides good reassurance that a patient with atypical cervical smear have CIN 1. Diagn. Cytopathol. 2012.

Usefulness of repeat cytology at the time of first colposcopy

The value of repeat cytology in the detection of high‐grade preinvasive or invasive disease was analyzed at the time of colposcopy in cases of patients with abnormal referral cytology. A series of 136 patients with squamous abnormalities in their referral cytology, who had undergone repeat cytology and for whom outcome had been established, were included in the study. Final diagnosis consisted of 27 negative results (20%), 37 cases of CIN1 (27%), 31 CIN2 (23%), 39 CIN3 (29%), and 2 (1%) cases of squamous cell carcinoma (SCC). Referral and repeat cytology suggestive of atypical squamous cells cannot exclude high‐grade squamous intraepithelial lesion (ASC‐H), high‐grade squamous intraepithelial lesion (HSIL) were findings significantly associated with a final diagnosis of CIN2 or worse. Sensitivity and positive predictive value of repeat cytology for the histological diagnosis of significant histological neoplasia (CIN2 or worse) were 81.9% and 77.6%, respectively. In women with referral cytology findings of atypical squamous cells of undetermined significance or low‐grade squamous intraepithelial lesion (ASC‐US/LSIL), repeat cytology was suggestive of HSIL in 20% of cases (11/54), and in 4% (2/54) biopsy was negative or CIN1, and the final diagnosis established by LLETZ was CIN3. Eight cases (10%) of HSIL in referral and repeat cytology in which biopsies were negative or insufficient were diagnosed as CIN3 or worse in the final diagnosis. Repeat cytology would have changed therapeutic management in 4 and 10%, respectively, of patients included as ASC‐US/LSIL and ASC‐H/HSIL in referral cytology. Diagn. Cytopathol. 2009.

Human papillomavirus genotypes 68 and 58 are the most prevalent genotypes in women from quilombo communities in the state of Maranhão, Brazil

OBJECTIVES To determine the frequency of human papillomavirus (HPV) types and behavioral characteristics related to cytological abnormalities in women descendants of slaves, who live in isolated communities known as quilombos in the state of Maranhão, Brazil. METHODS Cervicovaginal specimens of 353 women were analyzed by conventional cytology and genotyping. HPV detection and genotyping was performed using a linear array HPV genotyping test kit. Behavioral factors and their association with cytological abnormalities were analyzed, as well as the association between cytological abnormalities and HPV infection. RESULTS The frequency of HPV infection was 13%, and infection with high-risk HPV types was more frequent than with low-risk types (10.2% vs. 2.8%). The most prevalent genotypes were HPV 68 (3.1%) and HPV 58 (2.6%). HPV-positive women were 6.5 times more likely than HPV-negative women to be diagnosed with cytological abnormalities. There was a significant association between HPV infection and the presence of cytological abnormalities in women 31-40 years of age and in women 51-60 years of age. CONCLUSIONS A distinct profile of high-risk HPV genotypes was detected, with predominance of types 68 and 58. It is possible that the results of the present study are due to specific characteristics of the population, which is geographically isolated and maintains conservative sexual habits.

Null polymorphisms in GSTT1 and GSTM1 genes and their associations with smoking and cervical cancer

Human Papillomavirus (HPV) infection is the main risk factor for cervical cancer. However, other risk factors include smoking and genetic susceptibility. Glutathione-S-Transferases (GST) is enzymes involved in tobacco carcinogens metabolism and genes encoding these enzymes are highly polymorphic. The objective of this study was to compare the frequencies of GSTM1 and GSTT1 null polymorphisms in women with cervical cancer and in a control group, as well as the possible associations between such polymorphisms, cigarette smoking and the prognosis of cervical cancer. The series comprised 135 cervical cancer patients and 100 women without cancer. Genotypes were investigated by using polymerase chain reaction (PCR). The results were compared using the Chi-square test or Fishers exact test, and survival analysis by Kaplan-Meier test and Log-rank. Among the cases, the frequency of GSTM1 gene null polymorphism was 22.2%, and for the GSTT1 gene it was 48.5%. Among the controls, the frequency of the GSTM1 gene null polymorphism was 45.0%, as for the GSTT1 it was 56.0%. Important association was demonstrated between smoking and cervical cancer (p=0.0062; OR=2.16). Differently from GSTM1, GSTT1 null polymorphism was not associated with cervical cancer risk in this study. GSTT1 null genotype was significantly associated to a worse prognosis. Overall survival rate for the cervical cancer group was 78.5% and, when stratified by genotypes, survival was higher in patients with positive genotypes, indicating a higher risk of death for those presenting dual nullity (p=0.031; RR=2.458).

Internal quality control indicators in cervical cytopathology of a university laboratory

To evaluate the internal quality control indicators and quality management programme in a university cytopathology laboratory.

Internal quality monitoring indicators of citopathological exams of Clinical Laboratory of Goias Pontifical Catholic University (PUC-GO)

Resumo Objetivo: Avaliar a qualidade dos exames citopatológicos do Laboratório Clínico da Pontifícia Universidade Católica de Goiás (LAC-PUC-GO), de acordo com os indicadores da qualidade da fase analítica para o exame citopatológico, utilizando os índices que avaliam a qualidade, de acordo com o recomendado pelo Ministério da Saúde. Métodos: Os dados foram coletados no DATASUS através do SISCOLO alimentado pelo banco de dados do LAC-PUC-GO no período de janeiro de 2009 a dezembro de 2013. Os índices dos diagnósticos citopatológicos foram realizados utilizando Manual de Gestão da Qualidade para Laboratório de Citopatologia. Resultados: Do total de 7.015 exames citopatológicos realizados no período de janeiro de 2009 a dezembro de 2013, 99,5% foram classificados como satisfatórios, 91,8% exames citopatológicos negativos, 0,5% insatisfatórios e 7,7% exames alterados. O índice de positividade analisado no período de cinco anos alcançou uma média de 7%. O percentual de exames compatíveis com HSIL apresentou uma média de 1% e encontra-se dentro do esperado pelos índices de rastreamento até 2%; o percentual ASC/satisfatório foi baixo em 2009 (3%) e 2010 (2%) e alto em 2013 (7%), enquanto que a média de todos os anos foi de 4%; já a média da razão do percentual de ASC/SIL dois manteve-se dentro dos limites recomendados. Conclusão: O monitoramento interno da qualidade é uma ferramenta usada no auxílio diagnóstico, garantindo assim uma maior acurácia dos exames citopatológicos.