RESUMO
OBJECTIVES: To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women. METHODS: We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based gel or a placebo gel to be self-applied every other day for the first month and before and after each intercourse during follow-up. Assessments were performed at 0.5, 1, 3, 6, 9 and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Intention-to-treat analyses were performed. RESULTS: Between January 2013 and June 2017, a total of 280 participants were randomly assigned to the carrageenan (n = 141) or the placebo (n = 139) arm. All participants were included in safety analyses, but three (1%) were excluded from efficacy analyses (HPV results unavailable for two participants in the carrageenan and one participant in the placebo arm). The median follow-up time was 9.2 months (interquartile range, 1.9-13.2 months). A total of 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm became infected by at least one new HPV type (hazard ratio = 0.64, 95% confidence interval = 0.45-0.89, p 0.009). A total of 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p 0.02), none of which was deemed related to the gels. CONCLUSIONS: Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women.
Assuntos
Carragenina , Géis , Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Doenças do Colo do Útero/prevenção & controle , Doenças do Colo do Útero/virologia , Administração Intravaginal , Adulto , Método Duplo-Cego , Feminino , HumanosRESUMO
BACKGROUND AND AIMS: With the debate over extent of lymphadenectomy in endometrial cancer, sentinel lymph node (SLN) mapping may provide a focused approach to evaluate the most relevant lymph nodes (LN) while minimizing the complications. We evaluated SLN mapping using filtered technetium(99), indocyanine green (ICG), and blue dye. METHODS: Prospective evaluation of 100 patients who underwent SLN mapping by using submucosal and deep stromal cervical injections of technetium(99), ICG, and blue dye as part of the staging for endometrial cancer. RESULTS: 286 SLNs were mapped (2.9 per patient) in 92% of patients. The bilateral detection rate was 76%. ICG had a significantly higher SLN detection rate than blue dye in both overall (87% vs 71%, respectively; p=0.005) and bilateral (65% vs 43%, respectively; p=0.002) detection, but similar SLN detection rates compared to technetium(99) in both overall (87% vs 88%, respectively; p=0.83) and bilateral (65% vs 71%, respectively; p=0.36) detection. In eight cases, the SLN was in the para-aortic area and in 14 cases in the pre-sacral, hypogastric vein, or parametrial area. In nine cases, the SLN was positive for metastasis, and in seven cases the SLN was the only positive node. One SLN was falsely negative. No complications or anaphylactic reactions occurred. CONCLUSION: Intra-operative SLN mapping using cervical injection is feasible in patients with endometrial cancer and yields adequate detection rates. It allows mapping of SLNs in areas (pre-sacral, hypogastric vein, parametrial) not routinely sampled. Given the poorer performance of blue dye, surgeons may omit its use if a combination of ICG and technetium(99) is used.
Assuntos
Corantes , Neoplasias do Endométrio/patologia , Verde de Indocianina , Linfonodos/patologia , Biópsia de Linfonodo Sentinela/métodos , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Corantes/administração & dosagem , Neoplasias do Endométrio/reabilitação , Feminino , Humanos , Verde de Indocianina/administração & dosagem , Linfonodos/diagnóstico por imagem , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos/administração & dosagem , Coloide de Enxofre Marcado com Tecnécio Tc 99m/administração & dosagemRESUMO
The survival rates in childhood acute lymphoid leukemia (ALL) have improved dramatically; however, patients still suffer from a variety of drug-related toxicities. Individualized therapy regimens promise the least toxic therapy regimen with the best hematologic outcome. Our aim was to investigate whether increased individual glucocorticoid sensitivity due to the N363S polymorphism of the glucocorticoid receptor increased susceptibility to steroid-related toxicities during ALL therapy. A total of 346 pediatric ALL patients were involved in the present study. N363S carrier status was investigated by allele-specific PCR. Clinical and laboratory signs of glucocorticoid-related toxicities, Day 8 prednisone response, and 5-year event-free survival were analyzed and compared retrospectively. Thirty-two of the 346 patients were heterozygous carriers (9.2 %). Hepatotoxicity (31.3 vs. 11.2 %, p = 0.004, carriers and non-carriers, respectively) and glucose metabolism abnormalities (18.8 vs. 3.8 %, p = 0.001, carriers and non-carriers, respectively) were significantly more frequent among carriers. There was no difference in the incidence of hypertension and encephalopathy/psychosis among carriers and non-carriers. Carriers were also more prone to have a combination of toxicities. All 363S carriers were good prednisone responders (100 %) and had significantly better 5-year event-free survival rates (93.1 vs. 71.86 %, p = 0.012), whereas among non-carriers there were more poor prednisone responders (8.28 %) and worse 5-year event-free survival rates. Patients with the N363S polymorphism in the glucocorticoid receptor are more prone to steroid-related toxicity during ALL therapy and should be monitored more closely. Patients with N363S polymorphism of the glucocorticoid receptor may be appropriate candidates for inclusion in the design of individualized therapies.
Assuntos
Glucocorticoides/efeitos adversos , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Glucocorticoides/genética , Adolescente , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Feminino , Genótipo , Glucocorticoides/administração & dosagem , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidadeRESUMO
OBJECTIVE: There are currently multiple tests available for cervical cancer screening and the existing screening policies vary from country to country. No single approach will satisfy the specific needs and variations in risk aversion of all populations, and screening algorithms should be tailored to specific groups. We performed long term risk stratification based on screening test results and compared the accuracy of different tests and their combinations. METHODS: A longitudinal cohort study of the natural history of HPV infection and cervical neoplasia enrolled 2462 women from a low-income population in Brazil. The interviews and cervical screening with cytology and HPV DNA testing were repeated according to a pre-established protocol and the subjects were referred for colposcopy and biopsy whenever high grade lesions were suspected. We compared the specificity, sensitivity and predictive values of each screening modality. Long term risk stratification was performed through time-to-event analyses using Kaplan-Meier analysis and Cox regression. RESULTS: The best optimization of sensitivity and specificity was achieved when using dual testing with cytology and HPV DNA testing, whereby the screening test is considered positive if either component yields an abnormal result. However, when allowing 12months for the detection of lesions, cytology alone performed nearly as well. Risk stratification revealed that HPV DNA testing was not beneficial for HSIL cases, whereas it was for ASCUS and, in some combinations, for negative and LSIL cytology. CONCLUSION: Our results suggest that some high risk populations may benefit equally from cytology or HPV DNA testing, and may require shorter intervals between repeat testing.
Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Algoritmos , Brasil/epidemiologia , Estudos de Coortes , DNA Viral/análise , DNA Viral/genética , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
OBJECTIVE: To evaluate the outcome of various management schemes for HPV-related vulvar intraepithelial neoplasia (VIN, usual type). METHODS: Retrospective chart review of patients with histologically diagnosed grade 2/3-VIN who had at least one year of follow-up. The variables that were collected included patient characteristics, management modalities, and clinical outcome. RESULTS: Fifty patients with a median age of 45 years old were evaluated. The median duration of follow-up was 43.5 months (12-186). Complete response (CR) and partial response occurred in 28 (56%) and 4 (8%), respectively. Nineteen of 28 patients with CR recurred with VIN. Surgical excision yielded higher CR (77%) than did either ablational techniques (21-33%) or topical immunotherapy (33%). CONCLUSION: In this experience, surgical excision for VIN, usual type, resulted in better therapeutic success rates than other treatment modalities. Management schemes should be individualized based on extent of disease and patient compliance.
Assuntos
Carcinoma in Situ/terapia , Infecções por Papillomavirus/complicações , Lesões Pré-Cancerosas/terapia , Neoplasias Vulvares/terapia , Adjuvantes Imunológicos/uso terapêutico , Adulto , Idoso , Aminoquinolinas/uso terapêutico , Carcinoma in Situ/virologia , Ablação por Cateter/métodos , Feminino , Seguimentos , Humanos , Imiquimode , Terapia a Laser/métodos , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/virologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Vulvares/virologiaRESUMO
OBJECTIVES: The aim of the study was to confirm the endometrial safety and describe the bleeding profile of continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone in post-menopausal women. METHODS: An open, multicentre study was carried out in 290 healthy, non-hysterectomised post-menopausal women receiving oral continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone (Femoston-conti) for 1 year. Aspiration endometrial biopsies were performed at baseline and at the end of the study; those classified as hyperplasia or malignancy were considered treatment failures. RESULTS: Only one woman developed simple hyperplasia without atypia at the end of the study; the treatment failure rate was therefore 0.4%. Cross-sectional analysis showed that the percentage of women without bleeding increased from 71% during the first cycle to around 80% by the end of the study. Approximately 50% of the bleeding episodes occurred in the form of spotting; severe bleeding was rare and only seven women withdrew prematurely from the study due to uterine bleeding. Overall, 41% of the women were amenorrhoeic throughout the study. CONCLUSIONS: Continuous combined 1 mg 17beta-oestradiol and 5 mg dydrogesterone provides excellent endometrial safety and is associated with an acceptable bleeding profile.
Assuntos
Didrogesterona/administração & dosagem , Endométrio/efeitos dos fármacos , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Pós-Menopausa , Hemorragia Uterina/induzido quimicamente , Idoso , Estudos Transversais , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Didrogesterona/efeitos adversos , Estradiol/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the endometrial safety and bleeding patterns of 17 beta-estradiol sequentially combined with dydrogesterone. METHODS: Endometrial safety and bleeding patterns were assessed in 579 postmenopausal women randomized to oral treatment with placebo, 1 mg/day 17 beta-estradiol sequentially combined with 5 or 10 mg/day dydrogesterone for the last 14 days of each 28-day cycle, or 2 mg/day 17 beta-estradiol sequentially combined with 10 or 20 mg/day dydrogesterone for the last 14 days of each 28-day cycle. Treatment was continued for 26 cycles. Proliferative endometrium, endometrial hyperplasia and endometrial malignancy in the end-of-study biopsy were considered as inadequate progestational responses. RESULTS: Biopsies were not available in 137 women mainly because of an insufficient treatment period or non-compliance. An adequate progestational response was seen in more than 98% of the 442 women who underwent biopsy after treatment. Bleeding data were not available in 193 women, most of whom did not remain on treatment for the full 26 cycles. The 1-mg 17 beta-estradiol dose was associated with less cyclic and intermittent bleeding than the 2-mg dose. Higher doses of dydrogesterone were associated with a higher incidence of cyclic bleeds and a later day of onset, while duration, severity and regularity were similar in all groups irrespective of estradiol or dydrogesterone dose. CONCLUSION: Sequential combinations of 1 mg 17 beta-estradiol with 5 or 10 mg dydrogesterone and 2 mg 17 beta-estradiol with 10 or 20 mg dydrogesterone are associated with very good endometrial safety. The incidence of bleeding is lower with the 1-mg dose of 17 beta-estradiol.
Assuntos
Didrogesterona/administração & dosagem , Endométrio/anatomia & histologia , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Pós-Menopausa , Hemorragia Uterina , Idoso , Biópsia , Método Duplo-Cego , Didrogesterona/efeitos adversos , Estradiol/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , PlacebosRESUMO
BACKGROUND: The high rate of cervical cancer among aboriginal women of northern Canada has prompted the search for more aggressive methods to augment Papanicolaou (Pap) screening in this population. Nearly all cervical cancers result from oncogenic human papillomavirus (HPV) infections. This has generated interest for incorporating HPV testing into the current screening program. GOALS: To determine the prevalence of oncogenic HPVs in Nunavut, and to assess the association between HPV and squamous intraepithelial lesions (SIL). STUDY DESIGN: A cross-sectional study was conducted on the Pap-screened populations in 19 communities of Nunavut, Canada. Liquid-based cytology was used to screen for SIL. HPV testing was performed using the Hybrid Capture II assay. Correlates of HPV infection and SIL were assessed by logistic regression with control for potential confounders. RESULTS: In 1290 women ages 13 to 79 years, the prevalence rate was 26% for oncogenic HPV and 6.9% for SIL. The odds ratio for the association between HPV and SIL was 37.9 (95% CI, 17.7-80.8) after multivariate adjustment. This association increased markedly with increasing viral load. More than 90% of the women with squamous intraepithelial lesions had positive test results for HPV. More than 75% of the women who had positive test results for HPV but negative test results for SIL were younger than 30 years. CONCLUSION: The results of this study form the basis for further evaluation of the role that liquid-based cytology and HPV testing plays and will contribute to the strategy for cervical cancer prevention in Nunavut.
Assuntos
Carcinoma de Células Escamosas/epidemiologia , DNA Viral/isolamento & purificação , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Indígena Americano ou Nativo do Alasca/estatística & dados numéricos , Povo Asiático/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/prevenção & controle , Carcinoma de Células Escamosas/virologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Territórios do Noroeste/epidemiologia , Razão de Chances , Teste de Papanicolaou , Papillomaviridae/isolamento & purificação , Prevalência , Inquéritos e Questionários , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/estatística & dados numéricos , Saúde da Mulher , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologiaRESUMO
Organized screening has contributed to a decline in cervical cancer incidence and mortality over the past 50 years. However, women in developing countries are yet to profit extensively from the benefits of screening programs, and recent trends show a resurgence of the disease in developed countries. The past 2 decades have witnessed substantial progress in our understanding of the natural history of cervical cancer and in major treatment advances. Human papillomavirus (HPV) infection is now recognized as the main cause of cervical cancer, the role of coexisting factors is better understood, a new cytology reporting terminology has improved diagnosis and management of precursor lesions, and specific treatment protocols have increased survival among patients with early or advanced disease. Current research has focused on the determinants of infection with oncogenic HPV types, the assessment of prophylactic and therapeutic vaccines and the development of screening strategies incorporating HPV testing and other methods as adjunct to cytology. These are fundamental stepping stones for the implementation of effective public health programs aimed at the control of cervical cancer.
Assuntos
Papillomaviridae/patogenicidade , Infecções por Papillomavirus/complicações , Saúde Pública , Infecções Tumorais por Vírus/complicações , Neoplasias do Colo do Útero/virologia , Canadá/epidemiologia , DNA Viral/análise , Gerenciamento Clínico , Feminino , Humanos , Incidência , Programas de Rastreamento , Oncogenes , Infecções por Papillomavirus/diagnóstico , Revisão por Pares , Prognóstico , Fatores de Risco , Manejo de Espécimes , Análise de Sobrevida , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço VaginalRESUMO
BACKGROUND: Medical therapy for genital warts remains suboptimal. The topical interferon and cytokine inducer, imiquimod, has been proved effective for the treatment of external genital and perianal warts, but there is a substantial difference in the response rates between men and women. When 5% imiquimod cream is applied three times a week up to 16 weeks, approximately two thirds of women treated with imiquimod achieve complete clearance of genital warts, whereas only about one third of men clear completely. GOAL: This study was undertaken to determine whether more frequent application of topical imiquimod cream would improve the rate of genital wart clearance in men. STUDY DESIGN: A randomized treatment trial involving adult men with biopsy-proven genital warts was conducted at nine centers in the United States and Canada using four different application frequencies. RESULTS: Complete clearance rates during the 16-week treatment period were as follows for the different imiquimod treatment frequencies: three times a week (35 %), once daily (28 %), twice daily (24%), and three times a day (27%)(P = 0.88). The four treatment groups all showed comparable reductions in the total lesion area, with a median of more than a 90% reduction in the lesion area by the end of treatment. There was a significant increase in the incidence and severity of local skin reactions including erythema, vesicle formation, ulceration, and excoriation as the dosing frequency increased from three times a week to three times a day. CONCLUSIONS: In this study, the optimal dosage regimen was the approved three times a week regimen. More frequent application (up to three times a day) did not improve clearance and was associated with an increase in local adverse events.
Assuntos
Aminoquinolinas/uso terapêutico , Condiloma Acuminado/tratamento farmacológico , Indutores de Interferon/uso terapêutico , Adulto , Idoso , Aminoquinolinas/administração & dosagem , Aminoquinolinas/efeitos adversos , Anticorpos Antivirais/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Eritema/induzido quimicamente , Humanos , Imiquimode , Indutores de Interferon/administração & dosagem , Indutores de Interferon/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neopterina/sangue , Papillomaviridae/imunologia , Úlcera/induzido quimicamenteRESUMO
OBJECTIVES: To determine the endometrial safety of oral 17beta-oestradiol combined continuously with dydrogesterone in preventing endometrial proliferation. METHODS: The low dose group comprised three 52-week (13 cycles of 28 days) studies (two of which were double blind) using a 17beta-oestradiol dose of 1 mg daily combined with dydrogesterone 2.5, 5, 10 or 20 mg daily. The high dose group comprised two 24-week double-blind studies using a 17beta-oestradiol dose of 2 mg daily combined with dydrogesterone 2.5, 5, 10 or 15 mg daily. Endometrial safety was verified by aspiration endometrial biopsies. Inadequate progestational response was defined as proliferative endometrium, endometrial polyp, hyperplasia and carcinoma. RESULTS: Data was evaluable from 650 healthy postmenopausal women in the low dose group and 310 in the high dose group. Endometrial protection was achieved with dydrogesterone at doses of 5 mg or higher combined with 1 or 2 mg 17beta-oestradiol. The success rate was 97%, 97% and 98% in women receiving 1/5, 1/10 and 1/20 mg, respectively, and 95%, 98% and 91% in women receiving 2/5, 2/10 and 2/15 mg, respectively. A lower success rate was achieved with the 2.5 mg dydrogesterone dosage (93% in the 1/2.5 mg group and 85% in the 2/2.5 mg group) due to more cases of proliferative endometrium. None of the women in the low dose group developed hyperplasia or carcinoma; five (0.7%) had endometrial polyps. In the high dose group, one woman given 2.5 mg dydrogesterone developed hyperplasia; there were no cases of carcinoma. CONCLUSION: 5 mg daily dydrogesterone appears to be the lowest effective dose to ensure endometrial safety in a continuous combined regimen with 1 or 2 mg 17beta-oestradiol.
Assuntos
Didrogesterona/administração & dosagem , Didrogesterona/efeitos adversos , Endométrio/efeitos dos fármacos , Endométrio/patologia , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Terapia de Reposição Hormonal , Adulto , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
CONTEXT: Human papillomavirus (HPV) infection is believed to be the central cause of cervical cancer, although most of the epidemiological evidence has come from retrospective, case-control studies, which do not provide information on the dynamics of cumulative or persistent exposure to HPV infection. OBJECTIVE: To assess the risks of cervical neoplasia related to prior persistent HPV infections. DESIGN AND SETTING: Longitudinal study of the natural history of HPV infection and cervical neoplasia in women residing in the city of São Paulo, Brazil, which was conducted between November 1993 and March 1997 and involved repeated measurements of HPV and lesions with follow-up until June 2000. PARTICIPANTS: A total of 1611 women with no cytological lesions at enrollment and HPV test results available from the first 2 visits. MAIN OUTCOME MEASURE: Cervical specimens taken for Papanicolaou cytology and HPV testing every 4 months in the first year and twice yearly thereafter. Incident cervical cancer precursor lesions ascertained by expert review of all cytology smears. RESULTS: The incidence rate of squamous intraepithelial lesions (SILs) was 0.73 per 1000 women-months (95% confidence interval [CI], 0.5-0.9) among women free of HPV at the 2 initial visits and 8.68 (95% CI, 2.3-15.1) among women with HPV type 16 or 18 infections persisting over both visits. Relative to those negative for HPV oncogenic types at both initial visits, the relative risk (RR) of incident SIL was 10.19 (95% CI, 5.9-17.6) for persistent infections with any known oncogenic HPV types. The equivalent RR of incident high-grade SIL was 11.67 (95% CI, 4.1-33.3). The RRs of lesions were considerably higher for persistent infections with HPV type 16 or 18. CONCLUSION: A strong relationship exists between persistent HPV infections and SIL incidence, particularly for HPV types 16 and 18.
Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções Tumorais por Vírus/complicações , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adulto , DNA Viral/análise , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Análise Multivariada , Teste de Papanicolaou , Papillomaviridae/classificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Fatores de Risco , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologiaRESUMO
Evidence-based studies have shown that new techniques for cervical cancer screening have a higher diagnostic yield than conventional cervical cytology (Pap test). Automated screening devices that use liquid-based, thin-layer cytology and human papillomavirus DNA testing are likely to become the standard for routine primary screening for cervical cancer and its precursors in the 21st century. The increased initial expense of the new techniques will most certainly be absorbed by instituting longer intervals for safe primary screening, in both low-risk and high-risk populations. To make modern screening programmes even more effective, we must promote extensive public awareness campaigns about cervical cancer, a preventable disease.
Assuntos
Separação Celular/métodos , Neoplasias do Colo do Útero/patologia , Sondas de DNA de HPV , Diagnóstico por Computador , Feminino , Humanos , Programas de Rastreamento , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologiaRESUMO
Our objective was to determine whether the addition of human papillomavirus (HPV) testing to screening cytology improves the detection of cervical cancer precursors. Women of ages 18-69 years underwent conventional Pap cytology and HPV DNA testing in a multicenter study in Newfoundland, Canada. Those with positive cytology and/or HPV and a random sample of those with dual negative results were referred for colposcopy. The study enrolled 2098 women. The relative sensitivity of HPV testing was significantly higher than cytology for all-grade squamous intraepithelial lesions [SILs; 73%; 95% confidence interval (CI), 62-82] and high grade SILs (HSILs; 90%; 95% CI, 74-97) but had lower relative specificity (62% for all-grade SILs and 51% for HSILs) than most cytological cutpoints. The rate of combined correct results for all-grade lesions was higher for HPV testing (68.8%) than for any cytological cutpoint (equivocal, 52.3%; LSILs, 51.6%; HSILs, 44.5%). The combination of HPV and an LSIL cutpoint had a negative predictive value of 68% (95% CI, 52-80) for all SILs and 100% (95% CI, 91-100) for HSILs, while referring for colposcopy only 12% of the women. We concluded that HPV testing in conjunction with cytology improved the screening efficacy of cytology alone and may allow for a more effective and safe primary screening program with increased screening intervals.
Assuntos
Sondas de DNA de HPV , Programas de Rastreamento/métodos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adolescente , Adulto , Viés , DNA Viral/análise , Feminino , Humanos , Terra Nova e Labrador , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Sensibilidade e Especificidade , Infecções Tumorais por Vírus/diagnóstico , Neoplasias do Colo do Útero/prevenção & controleRESUMO
OBJECTIVE: To compare endocervical brushing with endocervical curettage with respect to diagnostic yield by histology and patient discomfort. METHODS: Nonpregnant women referred for colposcopy because of abnormal Papanicolaou test results were randomized to endocervical sampling with either a metal curette (endocervical curettage [ECC]) or an endocervical brush. Extensive endocervical canal brushing was performed. All samples were submitted for histologic study. Results were evaluated against the histologic findings in electroconization specimens in a masked fashion. Pain scores were recorded using Melzack's Present Pain Intensity Scale. RESULTS: During the study period, 315 patients were randomized to the techniques: 157 to ECC and 158 to endocervical brushing. Of the 315 patients, 147 also underwent electroconization. Overall false-positive rates were 28.6% for endocervical brushing and 30.8% for ECC. False positives were due to contamination of the endocervical sample by lesional epithelium near the external os. The proportion of scanty specimens obtained by endocervical brushing (7. 6%) was higher than that obtained by ECC (2.5%) (P =.041). One sample obtained by brushing was insufficient for diagnosis; none obtained by ECC were insufficient. There were no statistically significant differences in the median pain scores between the two groups. CONCLUSION: The techniques were similar in terms of diagnostic yield and patient discomfort. Endocervical brushing had lower false-positive rates than those reported in the literature for cytologic analysis. Although ECC remains the method of choice for evaluation of the endocervical canal, brushing is an acceptable alternative.
Assuntos
Colo do Útero/patologia , Curetagem , Manejo de Espécimes , Adulto , Colposcopia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
Management of endometrial precancers is compromised by longstanding debate over the natural history of endometrial hyperplasias and inconsistencies in their diagnosis. The recent demonstration that some hyperplasias, like cancers, are phenotypically monoclonal is useful in recognizing biological precancers. A clonal analysis has been undertaken of a series of 93 endometrial tissues and their morphology has been evaluated by subjective diagnostic classification and computerized morphometric analysis. A pathologist's diagnosis of atypical endometrial hyperplasia was highly associated with monoclonal growth. Both microsatellite-stable and microsatellite-unstable precancers were classified as atypical hyperplasias, indicating overlapping morphologies for these two groups. Diagnosis of non-atypical endometrial hyperplasias was not reproducible and identified a group of lesions equally likely to be monoclonal as polyclonal. Computerized morphometry resolved these lesions into monoclonal and polyclonal subgroups with a high degree of accuracy and reproducibility. The predictive value of morphometry was dominated by that fraction of the sample which consisted of stroma (volume percentage stroma). This can be measured manually and used to predict monoclonality when below the threshold value of 55%. This study shows that morphometric analysis reproducibly and precisely identifies monoclonal endometrial precancers from histological sections. It may serve, furthermore, to classify accurately lesions judged by pathologists as indeterminate (non-atypical hyperplasias). The material from this study (available at www.endometrium.org from March 1, 2000) and precisely defined architectural diagnostic criteria provide new tools for diagnostic standardization of endometrial precancers.
Assuntos
Diagnóstico por Computador/métodos , Neoplasias do Endométrio/patologia , Lesões Pré-Cancerosas/patologia , Linhagem da Célula , Feminino , Histocitoquímica/métodos , Humanos , Variações Dependentes do ObservadorRESUMO
⪠ABSTRACT: : To date the most widely used therapies for the treatment of external genital warts (EGWs) have been ablative techniques, some of which have serious side effects and result in high recurrence. This is frustrating for both patients and physicians. More recently, patient-applied therapies have become available, which offer several advantages over provider-administered therapies, and are generally preferred by the patients. The newest of these is imiquimod 5% cream. Its mode of action, stimulating the immune system to deal with the human papillomavirus (HPV), provides an effective treatment. Results obtained in clinical trials with imiquimod are described here, in the context of a recommended treatment protocol for EGWs. In addition, the potential for imiquimod to treat other HPV lesions is discussed. âª.
RESUMO
This article reports on a large longitudinal study, begun in 1993, of the natural history of human papillomavirus (HPV) infection and cervical neoplasia in a population of low-income women in São Paulo, Brazil, a city with one of the highest risks worldwide for cervical cancer. Known as the Ludwig-McGill cohort study, the epidemiological investigation focuses on persistent infection with oncogenic HPV types as the precursor event leading to cervical neoplasia. The objectives of this study are to: 1) study the epidemiology of persistent cervical HPV infection in asymptomatic women, 2) investigate whether persistent HPV infection increases risk of low-grade and high-grade cervical lesions, 3) search for determinants of persistent HPV infection, 4) search for molecular variants of HPV that may be associated with an increased risk of lesions, 5) investigate whether viral burden is correlated with persistent infections and with lesion risk, 6) study the antibody response to HPV as a predictor of persistence and lesion progression, and 7) examine the role of HLA typing and codon 72 p53 gene polymorphism in mediating HPV persistence and lesion severity. The study accrued 2,528 female subjects through March 1997. Subjects were followed up every 4 months in the first year, with twice-yearly return visits to take place in subsequent years. Participants undergo a questionnaire-based interview, have a cervical specimen taken for Pap cytology and HPV testing, and have a blood sample drawn for HPV antibody testing. A cervicography is performed once in the first year and every two years thereafter. In this article we describe the design and methods of the study, provide baseline cohort characteristics, and present a preliminary assessment of the prognostic value of baseline HPV status.
Assuntos
Infecções por Papillomavirus/virologia , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Idoso , Brasil/epidemiologia , Métodos Epidemiológicos , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/epidemiologia , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/virologiaRESUMO
OBJECTIVE: We aimed to provide simple methods for calculating expected sensitivity and specificity when an adjunctive test is added to a conventional test. STUDY DESIGN: Use of adjunctive methods for the triage of women with cervical abnormalities produces an apparent gain in sensitivity over Papanicolaou cytologic testing alone. This increase in sensitivity can be misleading, even if deemed significant by results of a statistical test. Combined testing prevents a loss in specificity but sometimes offers no real gain in sensitivity. A nominal increase in sensitivity always occurs by chance whenever an adjunctive test is used in parallel with a conventional one, even if the new test is totally random with respect to the disease being evaluated. RESULTS: Gains in sensitivity and losses in specificity have to be gauged against expected levels of these parameters when a random adjunctive test is coupled with Papanicolaou screening and not gauged against the performance of cytologic testing alone. CONCLUSION: We provide simple formulas for calculating the expected sensitivity and specificity in conditions of combination testing to provide more realistic baselines for assessment of the screening efficacy contributed by the adjunctive test.