Survival of a cohort of women with cervical cancer diagnosed in a Brazilian cancer center

OBJECTIVE: To assess overall survival of women with cervical cancer and describe prognostic factors associated. METHODS: A total of 3,341 cases of invasive cervical cancer diagnosed at the Brazilian Cancer Institute, Rio de Janeiro, southeastern Brazil, between 1999 and 2004 were selected. Clinical and pathological characteristics and follow-up data were collected. There were performed a survival analysis using Kaplan-Meier curves and a multivariate analysis through Cox model. RESULTS: Of all cases analyzed, 68.3% had locally advanced disease at the time of diagnosis. The 5-year overall survival was 48%. After multivariate analysis, tumor staging at diagnosis was the single variable significantly associated with prognosis (p<0.001). There was seen a dose-response relationship between mortality and clinical staging, ranging from 27.8 to 749.6 per 1,000 cases-year in women stage I and IV, respectively. CONCLUSIONS: The study showed that early detection through prevention programs is crucial to increase cervical cancer survival.

Avaliação da conduta conservadora na lesão intraepitelial cervical de alto grau

OBJETIVO: Analisar a associação entre a conduta conservadora em lesão intraepitelial cervical de alto grau com o índice de recidiva da neoplasia e faixa etária. MÉTODOS: Estudo transversal e retrospectivo realizado com 509 mulheres (15-76 anos) atendidas no período de 1996 a 2006, com colpocitologia oncótica alterada, em um serviço público de referência em Maringá, PR. Os dados foram coletados dos prontuários médicos e estudadas as variáveis diagnóstico definitivo, tipos de tratamento, ocorrência da lesão e recidivas, analisados por meio de testes de associação de qui-quadrado de Pearson e teste exato de Fisher. RESULTADOS: A lesão intraepitelial cervical de alto grau ocorreu em 168 casos; destes, 31 mulheres foram submetidas à amputação cônica, 104 a cirurgias de alta frequência, nove histerectomizadas e 24 receberam conduta conservadora. Dentre as mulheres com lesão de alto grau e tratadas de forma conservadora, oito (33,3%) recidivaram, enquanto dentre as submetidas à conduta não conservadora dez (6,9%) recidivaram, sendo essa diferença estatisticamente significante (p = 0,0009), RP = 4,8 (IC95% 2,11;10,93). Para aquelas que fizeram o seguimento clínico-citológico, três (30,0%) e, dentre as cauterizadas, cinco (35,7%) recidivaram no prazo de três anos, sem diferença significante (p = 0,5611). A recidiva abaixo e acima de 30 anos ocorreu, respectivamente, em sete (13,8%) e 11 (12,2%) mulheres (p = 0,9955). CONCLUSÕES: A idade da mulher não influencia o prognóstico de recidiva. O tratamento conservador deve ser indicado como conduta de exceção, dada a alta taxa de recidiva, e o seguimento deve ser rigoroso, com acompanhamento citológico e colposcópico de até três anos, período em que ocorre a maioria das recidivas.

Disparities in cervical and breast cancer mortality in Brazil

OBJECTIVE To analyze cervical and breast cancer mortality in Brazil according to socioeconomic and welfare indicators. METHODS Data on breast and cervical cancer mortality covering a 30-year period (1980-2010) were analyzed. The data were obtained from the National Mortality Database, population data from the Brazilian Institute of Geography and Statistics database, and socioeconomic and welfare information from the Institute of Applied Economic Research. Moving averages were calculated, disaggregated by capital city and municipality. The annual percent change in mortality rates was estimated by segmented linear regression using the joinpoint method. Pearson’s correlation coefficients were conducted between average mortality rate at the end of the three-year period and selected indicators in the state capital and each Brazilian state. RESULTS There was a decline in cervical cancer mortality rates throughout the period studied, except in municipalities outside of the capitals in the North and Northeast. There was a decrease in breast cancer mortality in the capitals from the end of the 1990s onwards. Favorable socioeconomic indicators were inversely correlated with cervical cancer mortality. A strong direct correlation was found with favorable indicators and an inverse correlation with fertility rate and breast cancer mortality in inner cities. CONCLUSIONS There is an ongoing dynamic process of increased risk of cervical and breast cancer and attenuation of mortality because of increased, albeit unequal, access to and provision of screening, diagnosis and treatment. 

Cervical cancer screening coverage in a high-incidence region

OBJECTIVE To analyze the coverage of a cervical cancer screening program in a city with a high incidence of the disease in addition to the factors associated with non-adherence to the current preventive program.METHODS A cross-sectional study based on household surveys was conducted. The sample was composed of women between 25 and 59 years of age of the city of Boa Vista, RR, Northern Brazil who were covered by the cervical cancer screening program. The cluster sampling method was used. The dependent variable was participation in a women’s health program, defined as undergoing at least one Pap smear in the 36 months prior to the interview; the explanatory variables were extracted from individual data. A generalized linear model was used.RESULTS 603 women were analyzed, with an mean age of 38.2 years (SD = 10.2). Five hundred and seventeen women underwent the screening test, and the prevalence of adherence in the last three years was up to 85.7% (95%CI 82.5;88.5). A high per capita household income and recent medical consultation were associated with the lower rate of not being tested in multivariate analysis. Disease ignorance, causes, and prevention methods were correlated with chances of non-adherence to the screening system; 20.0% of the women were reported to have undergone opportunistic and non-routine screening.CONCLUSIONS The informed level of coverage is high, exceeding the level recommended for the control of cervical cancer. The preventive program appears to be opportunistic in nature, particularly for the most vulnerable women (with low income and little information on the disease). Studies on the diagnostic quality of cervicovaginal cytology and therapeutic schedules for positive cases are necessary for understanding the barriers to the control of cervical cancer.

Waiting time for radiotherapy in women with cervical cancer

ABSTRACT OBJECTIVE To describe the waiting time for radiotherapy for patients with cervical cancer. METHODS This descriptive study was conducted with 342 cervical cancer cases that were referred to primary radiotherapy, in the Baixada Fluminense region, RJ, Southeastern Brazil, from October 1995 to August 2010. The waiting time was calculated using the recommended 60-day deadline as a parameter to obtaining the first cancer treatment and considering the date at which the diagnosis was confirmed, the date of first oncological consultation and date when the radiotherapy began. Median and proportional comparisons were made using the Kruskal Wallis and Chi-square tests. RESULTS Most of the women (72.2%) began their radiotherapy within 60 days from the diagnostic confirmation date. The median of this total waiting time was 41 days. This median worsened over the time period, going from 11 days (1995-1996) to 64 days (2009-2010). The median interval between the diagnostic confirmation and the first oncological consultation was 33 days, and between the first oncological consultation and the first radiotherapy session was four days. The median waiting time differed significantly (p = 0.003) according to different stages of the tumor, reaching 56 days, 35 days and 30 days for women whose cancers were classified up to IIA; from IIB to IIIB, and IVA-IVB, respectively. CONCLUSIONS Despite most of the women having had access to radiotherapy within the recommended 60 days, the implementation of procedures to define the stage of the tumor and to reestablish clinical conditions took a large part of this time, showing that at least one of these intervals needs to be improved. Even though the waiting times were ideal for all patients, the most advanced cases were quickly treated, which suggests that access to radiotherapy by women with cervical cancer has been reached with equity.

Human papillomavirus detection in cervical dysplasias or neoplasias and in condylomata acuminaata by in situ hybridization with biotinylated DNA probes

Specimens from cervical dysplasias or carcinomas and genital condylomata acuminata were retrospectively analysed by in situ hybridization (ISH) with bioti-nylated DNA probes for human papillomavirus (HPV) types 6, 11, 16 and 18. In the control group no case was positive for HPV DNA. In mild/moderate dysplasias, 4 cases (14%) were positive for HPV 6 or 11 and 2 cases (7%), for HPV 16. In the severe dysplasia/in situ carcinoma group, 9 cases (31%) showed presence of DNA of HPV types 16 or 18. Six invasive carcinomas (20%) were positive for HPV type 16 or 18. Among condylomata acuminata, 22 cases (73%) were positive for HPV types 6 or 11. In all ISH-positive cases only one viral type was detected. No correlation between HPV DNA positivity and histological findings of HPV infection was observed. Although less sensitive than some other molecular biology techniques, in situ hybridization with biotinylated DNA probes proved to be simple and useful for detecting and typing HPV in samples routinely received for histopathological analysis.

Human papillomavirus genotypes in women with cervical cytological abnormalities from an area with high incidence of cervical cancer

It has been well demonstrated the relationship between the infection with high-risk human papillomavirus (HPVs) genotypes and cervical cancer. In Northeastern Argentina a high incidence of this pathology has been described and therefore a high prevalence of HPV infection is expected. In order to identify HPV genotypes associated with malignant and pre-malignant cervical lesions present in the area, 53 ecto-endo cervical cell specimens obtained from women with cytohistological alterations were studied by a PCR-RFLP technique. Out of 53 patients, 34 (64.2%) were positive for HPV infection, being HPV-16 (32.3%) the most frequently found genotype, followed by HPV-58 (14.7%), -6, -18 and -45 (5.9%), -33, -52, -53, -54, -56, -66, -MM4 and -LVX100 (2.9%). Also 5 cases of infection caused by multiple genotypes were found, which corresponded to 14.7% of the positive cases. Results indicate that besides HPV-16 and -18, the most prevalent high-risk HPV genotypes worldwide, others like -45 and -58 as well as co-infection cases are frequent between women of Northeastern Argentina, and a particular attention should be paid to this circumstance because it could be an epidemiological feature of regional importance and a useful information for a future vaccination program.

Human papillomavirus status and cervical abnormalities in women from public and private health care in Rio de Janeiro State, Brazil

This article reports the HPV status and cervical cytological abnormalities in patients attended at public and private gynecological services from Rio de Janeiro State. It also comments the performance of each HPV DNA tests used. A set of 454 women from private health clinics was tested by routine Capture Hybrid II HPV DNA assay. Among these, 58.4% presented HPV and nearly 90% of them were infected by high risk HPV types. However, this group presented few premalignant cervical lesions and no invasive cervical cancer was registered. We also studied 220 women from low income class attended at public health system. They were HPV tested by polymerase chain reaction using My09/11 primers followed by HPV typing with E6 specific primers. The overall HPV prevalence was 77.3%. They also showed a high percentage of high squamous intraepithelial lesion-HSIL (26.3%), and invasive cervical carcinoma (16.3%). HPV infection was found in 93.1% and 94.4% of them, respectively. The mean ages in both groups were 31.5 and 38 years, respectively. In series 1, HPV prevalence declined with age, data consistent with viral transient infection. In series 2, HPV prevalence did not decline, independent of age interval, supporting not only the idea of viral persistence into this group, but also regional epidemiological variations in the same geographic area. Significant cytological differences were seen between both groups. Normal and benign cases were the most prevalent cytological findings in series 1 while pre-malignant lesions were the most common diagnosis in the series 2. HPV prevalence in normal cases were statistically higher than those from series 1 (p < 0.001), indicating a higher exposure to HPV infection. Women from both samples were referred for previous abnormal cytology. However, socio-demographic evidence shows that women from series 1 have access to treatment more easily and faster than women from series 2 before the development of pre-malignant lesions. These data provides baseline support for the role of social inequalities linked to high risk HPV infection leading to cervical cancer. Broadly screening programs and the development of safe and effective vaccines against HPV would diminish the toll of this disease that affect mainly poor women.

Molecular detection of HPV 16 and 18 in cervical samples of patients from Belo Horizonte, Minas Gerais, Brazil

PURPOSE: The aim of this study was to investigate the frequency of HPV infection and the types 16 and 18 in cervical samples from patients attended at two public health services of the city of Belo Horizonte, MG. METHODS: Cervical samples from 174 patients were collected for cytopathological and molecular tests. HPV infection was searched by PCR utilizing MY09 and MY11 primers or HPV 16 and HPV 18 specific primers. RESULTS: Amongst the 174 samples analyzed, 20.7% presented squamous intraepithelial and/or invasive lesions detected on cytopathological analysis and of those, 94.4% were infected by HPV. HPV 16 was found in 20% of the cases of low-grade squamous intraepithelial lesions and in 40% and 50% of high-grade squamous intraepithelial lesion and squamous invasive carcinoma, respectively. HPV 18 was detected in 6.7% of the low-grade lesion samples and in two HPV16 co-infected samples. In 50% of the cases of high-grade lesion, the HPV type was not determined. CONCLUSION: The HPV 16 was the virus type more frequently detected. However, more than 50% of the positive samples at the cytopathological analysis were negative for HPV 16 and 18, indicating that possibly other virus types are present in relative high frequencies in the studied population.

Epstein Barr virus detection in cervical samples of women living with human immunodeficiency virus

Epstein Barr Virus (EBV) is transmitted commonly by saliva, but it has been found in genital secretions, which suggests sexual transmission and led researchers to connect EBV and cervical neoplasia. People living with human immunodeficiency virus (HIV) are reported to be at high risk of acquiring genital infections and cervical lesions. To verify the presence of EBV in the genital tract and/or it could affect cervical changes, we analyzed cervical smears from 85 HIV seropositive women for EBV DNA determination. EBV was only detected in two (2.3%) samples. The present study provides neither evidence for EBV as sexually transmitted infection nor discards this possibility.

AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION

SUMMARY High-risk human papillomavirus (hr-HPV) infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP). HPV frequency was 62.4% (88/141). The most common HPV were HPV16 (37%), HPV18 (16.3%) and HPV33/45(15.2%). An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%), low grade lesions (22.9%), high grade (57.1%) and carcinoma (93.1%) (p < 0.0001). A multivariate analysis was performed to evaluate an association between methylation, age, tobacco exposure, HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p < 0.0001), hr-HPV (p = 0.01), HSIL (p < 0.0007) and malignant lesions (p < 0.0001). Since viral infection and epigenetic alterations are related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer.

Analysis of molecular biology techniques for the diagnosis of human papillomavirus infection and cervical cancer prevention

The objective of the present study was to evaluate the usefulness of molecular methodologies to access human papillomavirus genome in the genital tract. Samples from 136 women aged 17 to 52 years old obtained from the Dr. Sérgio Franco Laboratories between 2000 and 2001, were analyzed by the hybrid capture assay and amplified by PCR with generic primers MY09/MY11 and specific primers for types 16, 18, 31, 33, 35, 58. Viral genome was detected in 71.3% of the samples by hybrid capture and 75% by amplification. When cytopathology was used as a reference method for screening lesions, hybrid capture (p=0) and amplification (p=0.002) presented positive association. The 3 methods showed absolute agreement when cytopathology confirmed papillomavirus infection and high grade intraepithelial lesion. Disagreements occurred for 10 cases: seven inflammatory cases positive by PCR and negative for hybrid capture and 3 low squamous intraepithelial lesions positive for hybrid capture but negative for amplification. In conclusion, hybrid capture was shown to be sensitive and specific enough for use in clinical routines. Moreover, the evaluation of viral load values obtained by this method were shown to be related to the severity of the lesion and merit further studies to analyze the possible association with risk of progression to malignancy.

Febre do viajante associada com adenite cervical e sororreatividade para Bartonella sp em paciente brasileira, após retorno da África do Sul

Um grande número de viajantes visita anualmente, por estudo, turismo ou trabalho o continente africano. Um caso de adenomegalia cervical e hepatoesplenomegalia associado à febre de duas semanas de duração com teste sorológico positivo para Bartonella sp em uma paciente de 22 anos do sexo feminino que retornou da África do Sul após realização de trabalho de campo com primatas em área silvestre é apresentado.

S100, CD68, and MHC class II molecule expression in cervical high- and low-grade HPV-induced lesions

INTRODUCTION: Some human papillomavirus (HPV) types are involved in malignant processes in the cervical epithelium, with 99% of cases attributed to oncogenic HPV infection. This study aimed to detect S100, CD68, and major histocompatibility complex class II (MHC-II) molecules in cervical uterine epithelial samples in patients with high- and low-grade lesions induced by HPV. METHODS: Fifty-eight samples from patients who were confirmed positive or negative for high-risk oncogenic HPV DNA, had histopathological diagnosis of cervical intraepithelial neoplasia (CIN) of grades I, II, or III, or were negative for intraepithelial lesion or malignancy were subjected to immunohistochemistry reaction to S100 protein, CD68, and MHC-II (HLA-DR alpha chain). RESULTS: The presence of MHC-II predominated in samples exhibiting histopathological alterations (p < 0.05). S100 detection was more numerous in carcinoma samples (CIN III) (75%). Presence of this protein correlated significantly (p < 0.05) with histopathological findings and viral load. CONCLUSIONS: A small expression of CD68 was observed, which may be explained by the observation in our study having been made on random microscopic fields and not on specific areas. The findings, such as the presence of S100 protein and MHC-II expression in samples with histological alterations, could suggest that the immune system fails to control HPV replication at the early stages of infection. Further studies with larger prospective data are necessary to confirm this result.