Recurrence of cervical intraepithelial neoplasia in human immunodeficiency virus-infected women treated by means of electrosurgical excision of the transformation zone (LLETZ) in Rio de Janeiro, Brazil.

CONTEXT AND OBJECTIVE: Human immunodeficiency virus (HIV)-infected women have higher incidence, prevalence, persistence and recurrence of pre-invasive cervical lesions (CIN II or III). The aim here was to investigate the risk of recurrence of CIN II/III among HIV-infected women (HIV+) and uninfected women in a cohort treated by means of large-loop excision of the transformation zone (LLETZ). DESIGN AND SETTING: Cohort study conducted at Instituto Fernandes Figueira/Fundação Oswaldo Cruz (IFF/Fiocruz). METHODS: 60 HIV+ and 209 HIV-negative patients were included in a cohort for follow-up after undergoing LLETZ to treat CIN II/III. A histopathological diagnosis of CIN II/III during the follow-up was taken to constitute recurrence. The following possible confounding variables were assessed: age at treatment and at end of follow-up; histological grade of intraepithelial disease treated; surgical margin involvement; adequacy of colposcopy during the follow-up; CD4+ lymphocyte count; HIV viral load; and type of antiretroviral therapy. RESULTS: Among the 60 HIV+ women, six showed recurrent disease during the follow-up. However, among the 209 HIV-negative women, seven showed a new precursor lesion. The relative risk of disease recurrence in the HIV+ women was 4.21 (95% CI = 1.42 to 12.43). The Kaplan-Meyer curve showed that the risk of recurrence was significantly higher among HIV+ women (log-rank test: P = 0.0111). CONCLUSION: The HIV+ women in our cohort presented a risk of CIN II/III recurrence at least 42% higher than among the HIV-negative women. These patients should form part of a rigorous screening and follow-up protocol for identification and appropriate treatment of cervical cancer precursor lesions.

Recurrence of cervical intraepithelial neoplasia in human immunodeficiency virus-infected women treated by means of electrosurgical excision of the transformation zone (LLETZ) in Rio de Janeiro, Brazil / Recorrencia de neoplasias intraepiteliais cervicais em mulheres infectadas com o virus da imunodeficiencia humana tratadas pela exerese eletrocirurgica da zona de transformacao (EZT) no Rio de Janeiro, Brasil

CONTEXT AND OBJECTIVE: Human immunodeficiency virus (HIV)-infected women have higher incidence, prevalence, persistence and recurrence of pre-invasive cervical lesions (CIN II or III). The aim here was to investigate the risk of recurrence of CIN II/III among HIV-infected women (HIV+) and uninfected women in a cohort treated by means of large-loop excision of the transformation zone (LLETZ). DESIGN AND SETTING: Cohort study conducted at Instituto Fernandes Figueira/Fundação Oswaldo Cruz (IFF/Fiocruz). METHODS: 60 HIV+ and 209 HIV-negative patients were included in a cohort for follow-up after undergoing LLETZ to treat CIN II/III. A histopathological diagnosis of CIN II/III during the follow-up was taken to constitute recurrence. The following possible confounding variables were assessed: age at treatment and at end of follow-up; histological grade of intraepithelial disease treated; surgical margin involvement; adequacy of colposcopy during the follow-up; CD4+ lymphocyte count; HIV viral load; and type of antiretroviral therapy. RESULTS: Among the 60 HIV+ women, six showed recurrent disease during the follow-up. However, among the 209 HIV-negative women, seven showed a new precursor lesion. The relative risk of disease recurrence in the HIV+ women was 4.21 (95% CI = 1.42 to 12.43). The Kaplan-Meyer curve showed that the risk of recurrence was significantly higher among HIV+ women (log-rank test: P = 0.0111). CONCLUSION: The HIV+ women in our cohort presented a risk of CIN II/III recurrence at least 42% higher than among the HIV-negative women. These patients should form part of a rigorous screening and follow-up protocol for identification and appropriate treatment of cervical cancer precursor lesions. .

CONTEXTO E OBJETIVOS: Mulheres infectadas pelo vírus da imunodeficiência humana (HIV) apresentam maior incidência, prevalência, persistência e recorrência após tratamentos de lesões pré-invasivas do colo uterino (NIC II ou III). O objetivo foi verificar o risco de recorrência de NIC II/III em mulheres infectadas pelo HIV (HIV+) e não infectadas (HIV-) em uma coorte tratada pela exérese eletrocirúrgica da zona de transformação do colo uterino (EZT). TIPO DE ESTUDO E LOCAL: Estudo de tipo coorte realizado no Instituto Fernandes Figueira/Fundação Oswaldo Cruz (IFF/Fiocruz). MÉTODOS: 60 HIV+ e 209 HIV- foram incluídas em uma coorte após terem sido submetidas à EZT para tratamento de NIC II/III. Foi considerado como recorrência o diagnóstico histopatológico de NIC II/III. Foram estudadas as seguintes variáveis possivelmente confundidoras: idade no tratamento e ao final do seguimento, grau histológico da doença intra-epitelial tratada, comprometimento de margens, adequação da colposcopia no seguimento, contagem de linfócitos CD4+, carga viral de HIV e tipo de terapia antiretroviral. RESULTADOS: Dentre as 60 mulheres HIV+, 6 apresentaram doença recorrente durante o seguimento. De 209 HIV-, 7 apresentaram uma nova lesão precursora. O risco relativo de recorrência de doença nas HIV+ foi de 4,21 (IC 95% 1,42-12,43). Uma curva de Kaplan-Meyer mostra que o risco de recorrência é significativamente maior em mulheres HIV+ (teste de log-rank: P = 0,0111). CONCLUSÃO: Mulheres HIV+ em nossa coorte apresentaram risco de recorrência pelo menos 42% maior do que mulheres HIV-. Essas pacientes devem fazer parte de um protocolo de rastreio e acompanhamento rigoroso para identificação e tratamento adequado das lesões precursoras do câncer ...

Risk of persistent high-grade squamous intraepithelial lesion after electrosurgical excisional treatment with positive margins: a meta-analysis.

CONTEXT AND OBJECTIVE: Even if precursor lesions of cervical cancer are properly treated, there is a risk of persistence or recurrence. The aim here was to quantify the risks of persistence of high-grade intraepithelial squamous lesions, one and two years after cervical electrosurgical excisional treatment with positive margins. DESIGN AND SETTING: Systematic review of the literature and meta-analysis at Instituto Fernandes Figueira. METHODS: This meta-analysis was on studies published between January 1989 and July 2009 that were identified in Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they were cohort studies on electrosurgical excisional treatment of high-grade squamous intraepithelial lesions with a minimum follow-up of one year, a histopathological outcome of persistence of these lesions and a small risk of bias. RESULTS: The search identified 7,066 articles and another 21 in the reference lists of these papers. After applying the selection and exclusion criteria, only four articles were found to have extractable data. The risk of persistence of high-grade intraepithelial lesions after one year was 11.36 times greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001) in patients with positive margins and after two years, was four times greater (95% CI: 0.996-16.164), although without statistical significance. CONCLUSION: This meta-analysis confirms the importance of positive margins as an indicator of incomplete treatment after the first year of follow-up and highlights the need for appropriately chosen electrosurgical techniques based on disease location and extent, with close surveillance of these patients.

Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests.

CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6% to 12%. The HPV-DNA positivity rate ranged from 64% to 83%; sensitivity for CIN3 detection ranged from 95.2% to 100%; and specificity was available in two studies (27% and 52%). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33% and 90.8%); and specificity was available in one study (53%). CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.

Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests / Métodos de triagem colposcópica para detecção de neoplasia intraepitelial cervical grau 3 após diagnóstico citopatológico de lesão intraepitelial escamosa de baixo grau: uma revisão sistemática de testes diagnósticos

CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6 percent to 12 percent. The HPV-DNA positivity rate ranged from 64 percent to 83 percent; sensitivity for CIN3 detection ranged from 95.2 percent to 100 percent; and specificity was available in two studies (27 percent and 52 percent). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33 percent and 90.8 percent); and specificity was available in one study (53 percent). CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.

CONTEXTO E OBJETIVO: O desempenho do teste de DNA-HPV (ácido desoxirribonucleico-papilomavírus humano) oncogênico estratificado por idade para triagem de lesão intraepitelial escamosa de baixo grau (LSIL) demanda investigação. O objetivo do estudo foi avaliar e comparar o desempenho, para detecção de neoplasia intraepitelial cervical (NIC3), do teste de DNA-HPV oncogênico e da citologia de repetição estratificados por idade (ponto de corte 35 anos), para triagem de LSIL. TIPO DE ESTUDO E LOCAL: Revisão sistemática da literatura. Foram identificados estudos em nove bases de dados eletrônicas e listas de referências dos artigos recuperados. MÉTODOS: Critérios de elegibilidade: citologia inicial LSIL, realização do teste de DNA-HPV oncogênico e da citologia de repetição e detecção de NIC3. A diretriz QUADAS (Quality Assessment of Diagnostic Accuracy Studies) foi utilizada para avaliação da qualidade. As informações foram sintetizadas qualitativamente. RESULTADOS: Dentre 7.776 estudos, 284 eram pertinentes ao tema e três atenderam aos critérios de elegibilidade. A prevalência de NIC3 apresentou variação entre 6 por cento e 12 por cento. A taxa de positividade do teste de DNA-HPV apresentou variação entre 64 por cento e 83 por cento; a sensibilidade para NIC3 apresentou variação entre 95,2 por cento e 100 por cento; a especificidade estava disponível em dois estudos (27 por cento e 52 por cento). A sensibilidade da citologia de repetição (ponto de corte ASCUS - células escamosas atípicas de significado indeterminado) estava disponível em dois estudos (33 por cento e 90,8 por cento); a especificidade estava disponível em um estudo (53 por cento). CONCLUSÕES: Não existem, atualmente, evidências científicas disponíveis para comprovar que, em mulheres com 35 anos ou mais e citologia LSIL, a triagem colposcópica com teste de DNA-HPV oncogênico apresenta melhor desempenho para detecção de NIC3 do que a repetição citológica.

Risk of persistent high-grade squamous intraepithelial lesion after electrosurgical excisional treatment with positive margins: a meta-analysis / Risco de persistência da lesão intraepitelial escamosa de alto grau após tratamento excisional eletrocirúrgico com margens comprometidas: uma metanálise

CONTEXT AND OBJECTIVE: Even if precursor lesions of cervical cancer are properly treated, there is a risk of persistence or recurrence. The aim here was to quantify the risks of persistence of high-grade intraepithelial squamous lesions, one and two years after cervical electrosurgical excisional treatment with positive margins. DESIGN AND SETTING: Systematic review of the literature and meta-analysis at Instituto Fernandes Figueira. METHODS: This meta-analysis was on studies published between January 1989 and July 2009 that were identified in Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they were cohort studies on electrosurgical excisional treatment of high-grade squamous intraepithelial lesions with a minimum follow-up of one year, a histopathological outcome of persistence of these lesions and a small risk of bias. RESULTS: The search identified 7,066 articles and another 21 in the reference lists of these papers. After applying the selection and exclusion criteria, only four articles were found to have extractable data. The risk of persistence of high-grade intraepithelial lesions after one year was 11.36 times greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001) in patients with positive margins and after two years, was four times greater (95% CI: 0.996-16.164), although without statistical significance. CONCLUSION: This meta-analysis confirms the importance of positive margins as an indicator of incomplete treatment after the first year of follow-up and highlights the need for appropriately chosen electrosurgical techniques based on disease location and extent, with close surveillance of these patients.

CONTEXTO E OBJETIVO: As lesões precursoras do câncer de colo uterino, mesmo se tratadas adequadamente, têm risco de persistirem ou recidivarem. O objetivo foi quantificar o risco de persistência da lesão intraepitelial escamosa de alto grau (HSIL) em um e dois anos após tratamento excisional eletrocirúrgico do colo uterino com margens comprometidas. TIPO DE ESTUDO E LOCAL: Revisão sistemática da literatura e metanálise no Instituto Fernandes Figueira. METÓDO: Metanálise de estudos publicados entre janeiro de 1989 e julho de 2009 identificados em Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, Isis Web of Science e Sigle. Os artigos eram selecionados se fossem estudos tipo coorte sobre tratamento excisional eletrocirúrgico de HSIL com acompanhamento mínimo de um ano e tivessem como desfecho histopatológico a persistência de HSIL com pequeno risco de viés. RESULTADOS: Foram identificados 7.066 artigos e mais 21 nas listas de referências desses artigos. Após aplicação de critérios de seleção e de exclusão, somente quatro artigos ofereciam dados passíveis de extração. O risco de persistência da HSIL em um ano foi 11.36 vezes maior nas pacientes com margens comprometidas (intervalo de confiança, IC 95%: 5.529-23.379; P < 0,0001) e, em dois anos, chegou a quatro vezes, embora sem significância estatística (IC 95% 0.996-16.164). CONCLUSÃO: Esta metanálise confirma a importância de margem comprometida como indicador de tratamento incompleto no primeiro ano e ressalta a necessidade de uma adequada escolha da técnica eletrocirúrgica em função da localização e extensão da doença e um acompanhamento adequado dessas pacientes.