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ABSTRACT Background: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. Methods: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. Results: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). Conclusions: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.
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Breast cancer is the leading cause of cancer death among women worldwide. Multiple extrinsic and intrinsic factors are associated with this disease's development. Various research groups worldwide have reported the presence of human papillomavirus (HPV) DNA in samples of malignant breast tumors. Although its role in mammary carcinogenesis is not fully understood, it is known that the HPV genome, once inserted into host cells, has oncogenic capabilities. The present study aimed to detect the presence of HPV DNA in 116 breast tissue biopsies and classify them according to their histology. It was found that 50.9% of the breast biopsies analyzed were malignant neoplasms, of which 74.6% were histologically classified as infiltrating ductal carcinoma. In biopsies with non-malignant breast disease, fibroadenoma was the most common benign neoplasm (39.1%). Detection of HPV DNA was performed through nested PCR using the external primer MY09/11 and the internal primer GP5+/6+. A hybridization assay genotyped HPV. HPV DNA was identified in 20.3% (12/59) of malignant neoplasms and 35% non-malignant breast disease (16/46). It was also detected in 27.3% (3/11) of breast tissue biopsies without alteration. However, there are no statistically significant differences between these groups and the existence of HPV DNA (p = 0.2521). Its presence was more frequent in non-malignant alterations than in malignant neoplasias. The most frequent genotypes in the HPV-positive samples were low-risk (LR) HPV-42 followed by high-risk (HR) HPV-31.
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INTRODUCTION: Cervical and anus cancers have similarities: association with HPV infection, epithelial transformation zone, and precursor lesions. However, it is still unclear whether women with cervical cancer should be screened to identify high-grade squamous intraepithelial lesions and anal cancer. We aimed to identify high-risk HPV and cytological atypia in anal samples from women diagnosed with invasive squamous cell carcinoma of the cervix. STUDY DESIGN: We conducted a cross-sectional study between July 2016 and August 2017 in reference services in oncology in the State of Ceará, Brazil. We studied 59 patients diagnosed with frankly invasive squamous cell carcinoma of the cervix (at least stages IB) and 60 women in a control group. We performed liquid-based cytology (Surepath™) and HPV test (Cobas® 4800 System Test) of anal samples. To determine statistical significance with a confidence interval of 95%, we used Fisher's exact test and Student's t-test using the GraphPad Prism 7.0 software. RESULTS: The mean age in the control group was 56.7 ± 8.5 years, while in the group of women with cervical squamous cancer, it was 54.3 ± 14.8. The liquid-based cytology results of the satisfactory cases were: negative for intraepithelial lesion or malignancy (NLM): 51 cases (85%) in the control group and 38 (64.4%) in the study group (p = .0116). The HPV test was negative more frequently in the control group (n = 56, 93.3%) than in the study group (n = 17, 31.5%) (p < .0001). HPV 16 was the most frequent type (67.6%). CONCLUSIONS: There is a higher frequency of high-risk HPV and atypical cytology in women with cervical cancer than without lesions. Thus, this group should be considered as a target population for screening.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Anciano , Estudios Transversales , Femenino , Pruebas de ADN del Papillomavirus Humano , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/patologíaRESUMEN
BACKGROUND: HPV self-sampling has been widely supported by the scientific community following a strong body of literature on the subject. Self-sampling is important in cervical cancer screening as it has been shown to improve participation. It is well documented that HPV-testing has proven superior to cytology with regards to sensitivity in detection of CIN and cancer. The value of self-collected samples is reliant on the quality of the molecular testing performed, as well as the patients' preference in sampling procedure and compliance to follow up on positive test results. Due to the incompatibility of self-samples and cytology, triage of HPV-DNA positives by testing for molecular biomarkers is highly warranted. METHODS: Our objective was to compare the detection rate of genital Human Papillomavirus (HPV) infection in self- and clinician-collected samples by a 14-type HPV-DNA test and a 7-type mRNA E6/E7 test. RESULTS: Five hundred five women were recruited. Each study participant had two sample collection procedures performed upon the same visit, alternating order in execution of the self-collection or the clinician-taken procedure first or second, 1010 samples in total. HPV-DNA prevalence was 22.8% in self-collected versus 19.2% in clinician-collected samples (P = 0.19). Overexpression of mRNA E6/E7 from 7 HPV types was 7.1 and 6.3%, respectively (P = 0.71). The difference between HPV-DNA and HPV-mRNA positivity rates were statistically significant in both self-collected (22.8% versus 7.1%, P < 0.001) and clinician-collected samples (19.2% versus 6.3%, P < 0.001). Overall agreement between the two collection methods was fair, with a concordance rate of 78.2% (390/505), k = 0.34 (95% CI: 0.25-0.44), P < 0.001, for the HPV-DNA test and 92.5% (467/505), k = 0.40 (95% CI, 0.25-0.56), P < 0.001, for the mRNA test, respectively. 96.8% of the participants reported they felt confident carrying out the self-collection themselves, and 88.8% reported no discomfort at all performing the procedure. CONCLUSIONS: This comparative study of two sampling methods reports fair agreement of HPV positivity rates between the self-collected and clinician-collected specimens using Abbott hrHPV and PreTect HPV-Proofer'7 tests. Only one third of HPV-DNA positive women had overexpression of mRNA E6/E7. TRIAL REGISTRATION: ISRCTN77337300 .
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Técnicas de Diagnóstico Molecular/métodos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Manejo de Especímenes/métodos , Adulto , ADN Viral/genética , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , ARN Mensajero/genética , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virologíaRESUMEN
IMPACT STATEMENT: We are submitting data regarding the prevalence and type distribution of the HPV infection and the risk factors associated with it, which may provide a valuable reference to reinforce screening strategies, and to maintain HPV genotype surveillance in Mexico. We discuss the overall prevalence of HPV infection as detected in normal cytological samples stratified by age, different types of infection, and oncogenic capacity. One of the most important findings was that common HPV genotypes detected in healthy women were the genotype numbers: 6, 31, 16, and 56, likewise, smoking and having a history of more than three sexual partners over their lifetime, represented the main risk factors in this study. Furthermore, we found a low frequency of cytological abnormalities and CIN 1-3 in women with HR-HPV.
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Cuello del Útero/patología , Cuello del Útero/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Adulto , Anciano , Femenino , Genotipo , Humanos , México/epidemiología , Persona de Mediana Edad , Análisis Multivariante , Infecciones por Papillomavirus/genética , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To investigate factors associated with colposcopy attendance in HPV-positive women in São Paulo, Brazil. METHODS: We analyzed data from a prospective cohort of women positive for high-risk HPV (hr-HPV) undergoing cervical cancer screening in primary care services in São Paulo, Brazil. Non-pregnant women attending routine screening between December 2014 and March 2016 were offered an hr-HPV test, and those testing positive and aged 25 years or older were invited for colposcopy. Sociodemographic information was recorded at study enrollment. We compared variables between women who did and did not attend colposcopy within a logistic regression framework. RESULTS: Of 1537 hr-HPV-positive women, 1235 (80.4%) attended for colposcopy, with a median time from primary test to colposcopy of 132 days. Younger age (P<0.001) and concurrent negative cytology results (P=0.025) were associated with lower attendance. Women registered at units providing both the primary test and colposcopy were more likely to attend than those at units making external referrals (788/862 [91.4%] versus 447/675 [66.2%], P<0.001). CONCLUSION: Non-attendance for colposcopy may limit the success of future screening programs based on hr-HPV testing in Brazil. Transfer of colposcopy services to primary care is a simple and effective facilitator of attendance.
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Colposcopía , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/patología , Cooperación del Paciente , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Brasil , Estudios de Cohortes , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: The causal relationship between high-risk (hr) HPV infection and precancerous lesions or cervical cancer has led to the development of strategies to increase screening performance and prevent this cancer. The increased sensitivity of DNA-HPV testing compared to cervical cytology favors DNA-HPV testing as a primary screening test. Cervical cancer screening in Brazil is opportunistic, and this cancer remains a considerable health problem with a high proportion of diagnoses in advanced stages. This paper aims to describe the design and implementation of the Cervical Cancer Screening Program with primary DNA-HPV testing (CCSP-HPV) planned for Indaiatuba City (SP), Brazil; the strategies to achieve higher population coverage; and a study protocol for cost-effectiveness analyses. METHODS: The CCSP-HPV was designed based on successful guidelines that replaced cervical cytology-based screening by the DNA-HPV test performed at 5-year intervals. The screening will be performed for the female population aged 25-64 years cared for by the public health system and aim to reach 80% coverage after completing the first round. The chosen DNA-HPV test detects 14 hr-HPV types and genotypes HPV-16 and 18. All women with a negative test will be reassessed after five years. Women showing a positive test for HPV-16 and/or 18 will be referred for colposcopy. Those showing the other 12 hr-HPV types will be tested by cytology, and if any abnormality is detected, they will also be referred for colposcopy. The histopathologic evaluation will be reviewed by a pathologist panel and aided by p16 immunohistochemistry. A cost-effectiveness analysis will be performed by a Markov model comparing the cost of the new program and the screening performed by conventional cytology five years prior (2011-2016). DISCUSSION: The new screening program is considered a breakthrough for public health regarding cervical cancer, which is the third leading cause of cancer death among Brazilian women. Achieving at least 80% coverage will have the possibility to change this scenario. The proposed program will provide a modern cervical cancer screening method for women, and information about cost-effectiveness will help other similar places support the decision of implementing cervical cancer screening using the DNA-HPV test.
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ADN Viral/análisis , Detección Precoz del Cáncer/economía , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Brasil , Colposcopía/economía , Análisis Costo-Beneficio , Citodiagnóstico/economía , Detección Precoz del Cáncer/métodos , Femenino , Papillomavirus Humano 16/genética , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/economía , Infecciones por Papillomavirus/virología , Embarazo , Neoplasias del Cuello Uterino/economía , Neoplasias del Cuello Uterino/virología , Frotis Vaginal/economíaRESUMEN
Cervical cancer screening with human papillomavirus (HPV) DNA testing has been incorporated into El Salvador's national guidelines. The feasibility of home-based HPV self-collection among women who do not attend screening at the clinic (i.e., non-attenders) has been demonstrated, but cost-effectiveness has not been evaluated. Using cost and compliance data from El Salvador, we informed a mathematical microsimulation model of HPV infection and cervical carcinogenesis to conduct a cost-effectiveness analysis from the societal perspective. We estimated the reduction in cervical cancer risk, lifetime cost per woman (2017 US$), life expectancy, and incremental cost-effectiveness ratio (ICER, 2017 US$ per year of life saved [YLS]) of a program with home-based self-collection of HPV (facilitated by health promoters) for the 18% of women reluctant to screen at the clinic. The model was calibrated to epidemiologic data from El Salvador. We evaluated health and economic outcomes of the self-collection intervention for women aged 30 to 59â¯years, alone and in concert with clinic-based HPV provider-collection. Home-based self-collection of HPV was projected to reduce population cervical cancer risk by 14% and cost $1210 per YLS compared to no screening. An integrated program reaching 99% coverage with both provider- and home-based self-collection of HPV reduced cancer risk by 74% (compared to no screening), and cost $1210 per YLS compared to provider-collection alone. Self-collection facilitated by health promoters is a cost-effective strategy for increasing screening uptake in El Salvador.
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Análisis Costo-Beneficio , Detección Precoz del Cáncer/economía , Pruebas de ADN del Papillomavirus Humano , Modelos Teóricos , Infecciones por Papillomavirus/diagnóstico , Adulto , Colposcopía/economía , El Salvador , Femenino , Humanos , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
INTRODUCTION: The main cause of cervical cancer is an infection of keratinocytes in the basal layer of the stratified epithelium of the cervix by human papillomavirus (HPV). Other than in cervical samples, HPV DNA has been found in serum and other fluids but its origin is unclear. Extracellular vesicles (EV) could be a conveyance of viral DNA given their emerging role in cellular communication. The content of EV derived from cervical cells has not been properly explored and it is not known whether or not they contain HPV DNA. METHODS: We evaluated the DNA content of exosomes purified from cultures of HeLa cells by Next Generation Sequencing (NGS) and confirmed its presence by PCR. The presence of HPV DNA was also evaluated by PCR and NGS in EV from HPV-positive cervical samples without apparent lesion or with LSIL. RESULTS: We detected the integrated form of viral-DNA in exosomes from HeLa cells by NGS and confirmed its presence by PCR. The search for HPV sequences in EV obtained from cervical exudate samples without apparent lesion or with LSIL, where we expected to find the viral genome as an episome, indicated that HPV DNA, including the E6 and E7 oncogenes, is present in these EV. CONCLUSION: HPV DNA, including the viral oncogenes E6/E7, is found in exosomes regardless of the integration status of the virus in the infected cell.
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Cuello del Útero/virología , ADN Viral/aislamiento & purificación , Vesículas Extracelulares , Infecciones por Papillomavirus , Vesículas Extracelulares/virología , Femenino , Células HeLa , Humanos , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/diagnósticoRESUMEN
Human papillomavirus (HPV) is the etiological agent of cervical cancer. Also, HPV has been associated with anogenital cancer, oropharyngeal cancer, genital warts, and other dermatological diseases. HPV infects epithelial cells and their replication is closely linked to epithelial differentiation. The presence of HPV DNA in peripheral blood mononuclear cells (PBMC) has been reported in some patients with head and neck cancer, cervical cancer, and other genital diseases. However, the presence of HPV DNA in blood in asymptomatic subjects is still unresolved. The objective of this study was to evaluate the presence of HPV DNA in PBMC from asymptomatic blood donors. Blood samples were collected from 207 healthy Chilean blood donors. Genomic DNA was extracted from PBMC and HPV DNA detection was performed by real-time quantitative polymerase chain reaction assays with GP5+/6+ primers. HPV typing was carried out by genetic sequencing of a 140 to 150 bp fragment of the L1 gene. HPV DNA was detected in 6.8% (14/207) of blood donors. Single HPV infections were detected in seven blood donors. High-risk HPV was found in 6.3% (13/207) of cases: nine blood donors were infected with HPV-16, five with HPV-18, two with HPV-51, and one case was infected with either 32, 33, 45, 59, 66, 70, or 82. The median viral load value was 21.3 copies/mL blood or 13.4 HPV (+) cells per 10 4 PBMC. These results show that HPV DNA is present in PBMC from healthy blood donors and it suggests that blood could be a new route of HPV dissemination.
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Donantes de Sangre , ADN Viral/aislamiento & purificación , Leucocitos Mononucleares/virología , Infecciones por Papillomavirus/sangre , Adolescente , Adulto , Infecciones Asintomáticas , Chile/epidemiología , Cartilla de ADN/genética , Femenino , Genoma Viral , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Carga Viral , Adulto JovenRESUMEN
OBJECTIVE: To assess the cost-effectiveness of HPV-based screening and management algorithms for HPV-positive women in phase 2 of the Cervical Cancer Prevention in El Salvador (CAPE) demonstration, relative to the status quo of Pap-based screening. METHODS: Data from phase 2 of the CAPE demonstration (n=8000 women) were used to inform a mathematical model of HPV infection and cervical cancer. The model was used to project the lifetime health and economic outcomes of HPV testing every 5 years (age 30-65 years), with referral to colposcopy for HPV-positive women; HPV testing every 5 years (age 30-65 years), with immediate cryotherapy for eligible HPV-positive women; and Pap testing every 2 years (age 20-65 years), with referral to colposcopy for Pap-positive women. RESULTS: Despite slight decreases in the proportion of HPV-positive women who received treatment relative to phase 1, the health impact of screening in phase 2 remained stable, reducing cancer risk by 58.5%. As in phase 1, HPV testing followed by cryotherapy for eligible HPV-positive women remained the least costly and most effective strategy (US$490 per year of life saved). CONCLUSION: HPV-based screening followed by immediate cryotherapy in all eligible women would be very cost-effective in El Salvador.
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Detección Precoz del Cáncer/métodos , Tamizaje Masivo/economía , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Adulto , Análisis Costo-Beneficio , Detección Precoz del Cáncer/economía , El Salvador , Femenino , Humanos , Persona de Mediana Edad , Modelos Teóricos , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
Abstract Purpose the aim of this study was to evaluate the pattern of human papillomavirus (HPV) detection in an 11.3-year post-vaccination period in a cohort of adolescent and young women vaccinated or not against HPV 16/18. Methods a subset of 91 women from a single center participating in a randomized clinical trial (2001-2010, NCT00689741/00120848/00518336) with HPV 16/18 AS04- adjuvanted vaccine was evaluated. All women received three doses of the HPV vaccine (n = 48) or a placebo (n = 43), and cervical samples were collected at 6-month intervals. Only in this center, one additional evaluation was performed in 2012. Up to 1,492 cervical samples were tested for HPV-DNA and genotyped with polymerase chain reaction (PCR). The vaccine group characteristics were compared by Chi-square or Fisher exact or Mann-Whitney test. The high-risk (HR)-HPV 6-month-persistent infection rate was calculated. The cumulative infection by HPV group was evaluated by the Kaplan-Meier method and the log-rank test. Results the cumulative infection with any type of HPV in an 11.3-year period was 67% in the HPV vaccine group and 72% in the placebo group (p = 0.408). The longitudinal analysis showed an increase of 4% per year at risk for detection of HR-HPV (non-HPV 16/ 18) over time (p = 0.015), unrelated to vaccination. The cumulative infection with HPV 16/18 was 4% for the HPV vaccine group and 29% for the placebo group (p = 0.003). There were 43 episodes of HR-HPV 6-month persistent infection, unrelated to vaccination. Conclusions this study showed themaintenance of viral detection rate accumulating HR-HPV (non-HPV-16-18) positive tests during a long period post-vaccination, regardless of prior vaccination. This signalizes that the high number of HPV-positive testsmay be maintained after vaccination.
Resumo Objetivos avaliar o padrão de detecção do papilomavírus humano (HPV) em um período de 11.3 anos após a vacinação em uma coorte de adolescentes e mulheres jovens vacinadas ou não contra HPV 16/18. Métodos avaliou-se um subgrupo de 91 mulheres de um único centro, participantes de ensaio clínico randomizado (2001-2010, NCT00689741/00120848/00518336) com a vacina contra HPV 16/18 com adjuvante AS04. Todas as mulheres receberam três doses de vacina contra HPV (n = 48) ou placebo (n = 43), e tiveram amostras cervicais coletadas em intervalos de 6 meses. Somente neste centro, uma avaliação adicional foi realizada em 2012. Um total de 1.492 amostras cervicais foram testadas para DNA-HPV e genotipadas com reação em cadeia da polimerase (RCP). As características dos grupos de vacina contra HPV ou placebo foram comparadas pelo teste de Qui-quadrado ou teste exato de Fisher ou teste de Mann-Whitney. A infecção persistente por 6meses pelo HPV de alto risco (AR) foi calculada. A infecção cumulativa por grupo foi avaliada pelo método de Kaplan-Meier e pelo teste log-rank. Resultados a infecção cumulativa com qualquer tipo de HPV em11.3 anos foi de 67% no grupo vacina contra HPV e de 72% no grupo placebo (p = 0,408). A análise longitudinal mostrou um aumento de 4% ao ano no risco de detecção de HR-HPV (não-HPV 16/18) ao longo do tempo (p = 0,015), não relacionado com a vacinação. A infecção cumulativa com HPV 16/18 foi de 4% para o grupo vacina contra HPV e 29% para o grupo placebo (p = 0,003). Houve 43 episódios de infecção persistente por 6 meses por HR-HPV, não relacionados com a vacinação. Conclusões este estudo mostrou a manutenção da taxa de detecção viral, acumulando testes positivos de HR-HPV (não HPV-16-18) durante longo período pósvacinação, independentemente da vacinação prévia. Isto sinaliza que a alta positividade dos testes de HPV pode ser mantida após a vacinação.
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Humanos , Femenino , Papillomaviridae/aislamiento & purificación , Cuello del Útero/virología , Vacunas contra Papillomavirus , Factores de Tiempo , Estudios Prospectivos , Estudios de Seguimiento , Medición de Riesgo , Infecciones por Papillomavirus/prevención & control , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunologíaRESUMEN
ABSTRACT Previously, the screening for detection of cervical cancer was performed by simple cervicovaginal sample collected by the physician whenever the patient attended the medical consultation, and soon it was established as the annual"Pap smear". Since then, an elementary test has evolved into a complex process with multiple algorithms for the identification of invasive disease. The detection of human papillomavirus (HPV) has become part of the new screening recommendations, resulting in major changes in the guidelines. This review intends to emphasize the most important topics that are part of cervical cancer screening, including cervical cytology and HPV detection, and to discuss particular aspects of cervical cancer in Brazil. Despite the great benefits achieved by the cervical cancer screening programs with cytology and HPV test, there are still important issues to be discussed and improved in defining future strategies, including simplicity and possible application in different socioeconomic contexts, definition of the best test or tests to be applied and recommended interval, minimizing possible harms. After the establishment of screening algorithms well defined by leading organizations, management protocols should be disseminated among physicians and patients by education programs.
RESUMO Inicialmente, a triagem para detecção do câncer de colo uterino era feita por meio de uma simples amostra cervicovaginal colhida pelo médico, sempre que o paciente comparecia à consulta médica; logo se estabeleceu como"exame de Papanicolaou" anual. Desde então, um teste elementar evoluiu para um processo complexo, com múltiplos algoritmos para identificação de doença invasiva. A detecção do papilomavírus humano (HPV) tornou-se parte das novas recomendações de triagem, resultando em grandes mudanças nas diretrizes. Esta revisão pretende enfatizar os tópicos mais importantes que fazem parte do rastreamento do câncer de colo do útero, incluindo citologia cervical e detecção do HPV, bem como discutir aspectos particulares do câncer de colo do útero no Brasil. Apesar dos grandes benefícios alcançados pelos programas de rastreamento do câncer de colo uterino por meio do uso da citologia e do teste de HPV, existem ainda pontos importantes a serem discutidos e melhorados na definição de estratégias futuras, como simplicidade e possível aplicação em diferentes contextos socioeconômicos, definição do melhor teste ou testes a serem aplicados e intervalo recomendável, minimizando possíveis danos. Após o estabelecimento de algoritmos de rastreamento bem definidos pelas principais organizações, protocolos de manejo devem ser divulgados entre médicos e pacientes por programas de educação.
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Abstract Objectives To evaluate the incidence and factors associated with cervical intraepithelial neoplasia (CIN) and cervical infection by human papillomavirus (HPV) among HIV-positive and HIV-negative women. Methods A cohort of 103 HIV positive and 113 HIV negative women were monitored between October 2008 and February 2012, for at least one year. Procedures included cervical cytology, DNA/HPV detection by polymerase chain reaction, colposcopy with biopsy if necessary, followed by an interview for exposure characteristics data. CIN was based on the histopathological results. Results The incidence of CIN was of 8.8 and 4.6 cases/100 women-years in HIVpositive and HIV-negative women, respectively. HIV-positive women presented a hazard ratio (HR) of 2.8 for CIN and developed lesions earlier (0.86 year) than HIVnegative women (2 years) (p = 0.01). The risk of developing CIN decreased with age (HR = 0.9) and marital status (HR = 0.4). HPV patients presented a higher incidence of CIN when compared HIV-positive and HIV-negative women (p = 0.01). The incidence of HPV cervical infection was 18.1 and 11.4 cases/100 women-years in HIV-positive and HIV-negative women, respectively. Those HIV-positive presented earlier HPV infection (p = 0.002). The risk of developing HPV infection decreased with age and was higher among HIV-positive women. HPV 16 was the most common type in HIV-positive women, and also the type most closely associated with CIN in HIV-negative women. Conclusions HIV-positive women had a greater incidence of HPV and CIN, and in a shorter time interval. More rigorous and timely clinical control is required for this group.
Resumo Objetivos Avaliar a incidência e fatores associados com neoplasia intraepitelial cervical (NIC) e infecção cervical pelo Papiloma Vírus Humano (HPV) entre mulheres HIV positivas e negativas. Métodos Coorte de 103 mulheres positivas para o HIV e 113 negativas, que foram acompanhadas entre outubro de 2008 a fevereiro de 2012, com seguimento mínimo de um ano. Os procedimentos realizados foram coleta de material cervical para citologia oncótica e detecção do DNA/HPV pela reação em cadeia da polimerase, colposcopia seguida de biópsia, se necessário, e entrevista para obter dados e características de exposição. O diagnóstico de NIC foi baseado no resultado histopatológico das biópsias. Resultados A incidência pessoas-tempo de NIC foi de 8,8 e 4,6 casos/100 mulheresano para as mulheres HIV-positivas e HIV-negativas, respectivamente. As HIV-positivas apresentaram uma razão de risco (HR) de 2,8 para NIC e desenvolveram lesões mais precocemente (0,86 ano) do que as negativas (2 anos) (p = 0,01). O risco de desenvolver NIC diminuiu com a idade (HR = 0,9) e o estado civil (HR = 0,4). Pacientes com HPV apresentaram maior incidência de NIC, quando comparadas as mulheres HIVpositivas e as negativas (47,6 10,5%) (p = 0,01). A incidência de infecção cervical pelo HPV, por pessoa/tempo, foi de 18,1 e 11,4 casos/100 mulheres-ano, respectivamente para mulheres HIV-positivas e negativas. As HIV-positivas apresentaram HPV mais precocemente (p = 0,002). O risco de apresentar HPV diminuiu com a idade e foi maior entre as HIV-positivas. O HPV 16 foi o tipo mais comum entre as mulheres HIVpositivas. Conclusões As mulheres HIV-positivas tiveram maior incidência de HPV e NIC, e um menor intervalo de tempo. Controle clínico mais rigoroso e oportuno é requerido para este grupo.
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Humanos , Femenino , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virología , Seronegatividad para VIH , Seropositividad para VIH/complicaciones , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Incidencia , Estudios Prospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Human papillomavirus (HPV) DNA testing can be crucial for women who have limited access to traditional screening. The current study compared the results obtained through HPV DNA testing with those obtained through cytology-based screening. METHODS: A total of 3068 women aged 18 to 85 years were enrolled in an opportunistic cervical cancer screening program developed by the Barretos Cancer Hospital and performed by a team of health professionals working within a mobile unit from March to December 2012, followed by statistical analyses. For each patient, 2 different cervical samples were collected and preserved in a careHPV assay and SurePath medium, respectively. RESULTS: High-risk HPV (hr-HPV) DNA was detected in 10.0% of women, with the majority (86.7%) demonstrating no abnormal Papanicolaou test results. The following cytological samples were found to be hr-HPV positive: 8.2% of the normal samples; 39.4% of the samples with atypical squamous/glandular cells of undetermined significance; 38.5% of the samples with atypical squamous/glandular cells of undetermined significance, cannot exclude high-grade lesion; 55.3% of the samples with low-grade squamous intraepithelial lesions; and 100% of the samples with high-grade squamous intraepithelial lesions. Colposcopy examinations were performed among 33.4% of the women with positive results on at least 1 of the tests (HPV DNA positive and/or cytology with atypical squamous/glandular cells of undetermined significance, cannot exclude high-grade lesion or high-grade squamous intraepithelial lesions), and 59.5% of these women underwent biopsies. Among these samples, 18.2% were confirmed as cervical intraepithelial neoplasia. CONCLUSIONS: The careHPV test was demonstrated to be a feasible alternative to primary screening in low-resource settings accessed through the use of mobile units. Cancer Cytopathol 2016;124:581-8. © 2016 American Cancer Society.
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Pruebas de ADN del Papillomavirus Humano/estadística & datos numéricos , Tamizaje Masivo , Unidades Móviles de Salud/estadística & datos numéricos , Infecciones por Papillomavirus/diagnóstico , Lesiones Intraepiteliales Escamosas de Cuello Uterino/diagnóstico , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , ADN Viral/genética , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Prueba de Papanicolaou , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Pronóstico , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Neoplasias del Cuello Uterino/virología , Frotis Vaginal , Adulto Joven , Displasia del Cuello del Útero/virologíaRESUMEN
ABSTRACT Introduction: Studies conducted during the last years, using new technologies for viral detection, permit to consider human papillomavirus (HPV) an etiologic factor for cervical cancer. Besides the relation to genital regions, other anatomic sites have been associated with HPV, including head and neck regions. Objectives: To investigate the prevalence of HPV infection in 35 samples from paraffin-embedded tissues using polymerase chain reaction (PCR)-deoxyribonucleic acid (DNA) amplification, and correlate it with demographic, clinical, and morphological factors and prognosis. Materials and methods: All samples were first amplified with human β-globin gene primers. Samples with positive amplification were subjected to HPV-DNA detection with general GP5 and GP6 primers. Results Only 30 samples were amplified for the β-globin gene. No floor of mouth squamous cell carcinoma cases showed amplification of HPV DNA. Discussion: The absence of HPV-DNA amplification does not suggest that this virus is absent from the process of oral carcinogenesis, since the selected sample is not in the risk group for the development of oral cancer associated with HPV infection. Conclusions: No correlation was found between HPV infection and floor of mouth carcinogenesis, however further studies are necessary.
RESUMO Introdução: Estudos realizados durante os últimos anos permitem considerar a infecção pelopapilomavírus humano (HPV) um fator etiológico para o câncer cervical. Apesar da íntima relação desse vírus com as regiões genitais, outras localizações anatômicas têm sido associadas a tal infecção, inclusive as regiões de cabeça e pescoço. Objetivos: Investigar a prevalência da infecção pelo HPV em 35 amostras parafinadas de carcinoma espinocelular de assoalho de boca, utilizando a amplificação da reação em cadeia dapolimerase (PCR) como método de detecção do ácido desoxirribonucleico (DNA) viral, bem como correlacionar aspectos demográficos, clínicos e morfológicos com o prognóstico da doença. Materiais e métodos: Todas as amostras foram inicialmente amplificadas com o primerpara detecção do gene da β-globina humana. As que tiveram amplificação positiva para o gene da β-globina foram então submetidas à detecção do DNA viral com os primers GP5 e GP6. Resultados: Apenas 30 amostras foram amplificadas para o gene β-globin. Nenhuma das amostras de carcinoma de assoalho de boca demonstrou resultado positivo para amplificação do DNA viral. Discussão: Apesar de a influência do vírus na carcinogênese oral não ter sido comprovada devido à ausência de DNA viral nas amostras, a relação não pode ser descartada, uma vez que as amostras selecionadas não se encontravam em grupo de risco para o desenvolvimento de carcinoma espinocelular de boca associado à infecção pelo HPV. Conclusão: Não foi detectada relação entre a infecção pelo HPV e o carcinoma de assoalho de boca, no entanto mais estudos são necessários sobre o tema.
RESUMEN
BACKGROUND: We previously conducted a population-based screening trial of high-risk human papillomavirus (hrHPV) testing and conventional cytology, demonstrating higher sensitivity (92.7 % vs 22.1 % for CIN2+) but lower positive predictive value (10.5 % vs 23.9 %) of hrHPV testing. Here we report the performance of HPV16/18 genotyping to triage the hrHPV positive participants. METHODS: Women aged 25 years and older received hrHPV (Hybrid Capture 2) and Papanicolaou testing; positives by either test underwent colposcopy and directed biopsy, as did a sample of double-negatives. hrHPV positive women were reflex-tested with HPV16/18 genotyping (Digene HPV Genotyping PS Test). RESULTS: Among the 8,265 participants, 10.7 % were hrHPV positive, 1.7 % had ASCUS+ cytology, 1.2 % had CIN2+; 776 (88 %) hrHPV positive women had complete results, of whom 38.8 % were positive for HPV16 (24.0 %), HPV18 (9.7 %) or both (5.1 %). CIN2+ prevalence in HPV16/18 positive women (16.3 %, 95 % CI 12.3-20.9) was twice that of HPV16/18 negative women (8.0 %, 95 % CI 5.7-10.8). HPV16/18 genotyping identified 40.5 % of CIN2, 66.7 % of CIN3 and 75.0 % of cancers. Compared to hrHPV screening alone, HPV16/18 triage significantly reduced the referral rate (10.7 % vs 3.7 %) and the number of colposcopies required to detect one CIN2+ (9 vs 6). When HPV16/18 negative women with baseline ASCUS+ cytology were also colposcopied, an additional 14 % of CIN2+ was identified; referral increased slightly to 4.2 %. CONCLUSIONS: HPV16/18 triage effectively stratified hrHPV positive women by their risk of high-grade lesions. HPV16/18 positive women must be referred immediately; referral could be deferred in HPV16/18 negative women given the slower progression of non-HPV16/18 lesions, however, they will require active follow-up.
RESUMEN
PURPOSE: To investigate the prevalence of human papillomavirus (HPV) in cervical samples of pregnant and non-pregnant women in South-Brazil. METHODS: A prospective study of 91 pregnant and 92 non-pregnant women with no previous history of cervical dysplasia or cancer was carried out. Cervical samples for HPV testing and cytology were collected in each trimester of pregnancy and in the puerperium for pregnant women and at matched intervals for the non-pregnant women. All samples were analyzed through PCR with consensus primers GP5+/GP6+. Genotyping was performed using specific primers. To control for confounding factors, the analysis of multivariate logistic regression was applied. The measure of odds ratio (OR) and the 95 % confidence interval (95 % CI) were used. The level of statistical significance was set at 5 % (P ≤ 0.05). RESULTS: HPV DNA was detected in 23/91 (25.3 %) cervical samples from the pregnant women and in 12/92 (13 %) cervical samples from non-pregnant women (P = 0.035). There was a significant association among cervical HPV infection and young age, number of lifetime sexual partners, and the presence of abnormal cervical cytology. HPV16 and HPV18 were the viral types more frequently detected. Out of the 23 HPV-positive pregnant women, 17 (73.9 %) had normal cervical cytology. CONCLUSION: Our results suggest a higher prevalence of HPV infection in pregnant vs. non-pregnant women. This finding may be related to the relative immunosuppression observed in pregnant women, outlining the importance of the appropriate monitoring of the viral infection in this specific population.
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ADN Viral/análisis , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Adulto , Brasil/epidemiología , Femenino , Genotipo , Papillomavirus Humano 16/genética , Humanos , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/genética , Reacción en Cadena de la Polimerasa , Embarazo , Complicaciones Infecciosas del Embarazo/microbiología , Mujeres Embarazadas , Prevalencia , Estudios Prospectivos , Frotis Vaginal , Adulto JovenRESUMEN
Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30-65 years: (i) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); (ii) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and (iii) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by â¼ 60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP.
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Detección Precoz del Cáncer , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adulto , Colposcopía , Análisis Costo-Beneficio , El Salvador , Femenino , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Modelos Teóricos , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Embarazo , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Frotis VaginalRESUMEN
OBJECTIVE: To develop a prognostic model for women who underwent surgical treatment for cervical intraepithelial neoplasia. DESIGN: Cohort study. Patient inclusion and follow-up occurred retrospectively and prospectively. SETTING: Barretos Cancer Hospital, Barretos, São Paulo, Brazil. POPULATION: Women (n = 242) diagnosed with cervical intraepithelial neoplasia who were submitted to conization. METHODS: Immediately prior to surgical treatment, a cervical cytology sample was collected from each individual included in the study by endocervical brushing and stored in a preservative solution with methanol. A human papilloma virus-DNA test was conducted using an aliquot of the endocervical brushings. The surgical specimens were subjected to immunohistochemical analysis of p16 (immunohistochemical analysis 4a) protein expression. MAIN OUTCOME MEASURES: Two-year disease-free survival rates calculated for each study variable. Identified variables in the multivariate Cox model were used for elaboration of prognostic scores. RESULTS: Variables associated with outcome included age (p = 0.033), tobacco use (p < 0.001), final histopathological diagnosis (p = 0.007), surgical margins (p < 0.001), high-risk human papilloma virus status (p = 0.008), human papilloma virus-16 status (p < 0.001) and immunoexpression of p16 in the cytoplasm (p = 0.049). By the Cox model, independent risk factors for disease recurrence/persistence were: tobacco use (hazard risk = 3.0; 95% confidence interval 1.6-5.6), positive surgical margins (hazard risk = 3.2; 95% confidence interval 1.6-6.1), human papilloma virus-16 (hazard risk = 3.3; 95% confidence interval 1.6-6.9) and age over 45 years (hazard risk = 2.7; 95% confidence interval 1.1-6.6). CONCLUSIONS: Establishment of a prognostic score can represent a valuable tool for determining the risk of cervical intraepithelial neoplasia recurrence after conization. The use of clinical (age and tobacco use), pathological (surgical margins) and molecular (human papilloma virus-16 genotyping) factors can facilitate more appropriate patient follow up according to risk stratification.