RESUMO
There are few pathologic or molecular studies of penile precancerous lesions, and the majority refers to lesions associated with invasive carcinomas. Penile Intraepithelial Neoplasia (PeIN) is classified in two morphologically and distinctive molecular groups, non-HPV and HPV-related with special subtypes. The primary purpose of this international series was to classify PeIN morphologically, detect HPV genotypes and determine their distribution according to PeIN subtypes. A secondary aim was to evaluate the p16INK4a immunostaining as a possible HPV surrogate for high-risk HPV infection in penile precancerous lesions. Samples consisted of 84 PeIN cases, part of a retrospective cross-sectional analysis of 1095 penile carcinomas designed to estimate the HPV DNA prevalence in penile cancers using PCR and p16INK4a immunostaining. Penile Intraepithelial Neoplasia (PeIN) was classified in HPV-related (basaloid, warty-basaloid, warty, hybrid, and mixed subtypes) and non-HPV-related (differentiated), the former being the most frequent. PeIN subtypes were differentiated (non-HPV-related) and basaloid, warty-basaloid, warty, hybrid and mixed (HPV-related). Basaloid PeIN was the most commonly diagnosed subtype, and HPV16 was the most frequent HPV genotype detected. Warty-basaloid and warty PeIN showed a more heterogeneous genotypic composition. Most HPV genotypes were high-risk but low-risk HPV genotypes were also present in a few cases (4%). A single HPV genotype was detected in 82% of HPV positive cases. In contrast, multiple genotypes were detected in the remaining 18% of cases. The findings in this study support the paradigm that penile in situ neoplasia, like its invasive counterparts, is HPV dependent or independent and has distinctive morphological subtypes readily identified in routine practice. Considering that HPV16 is clearly the predominant type, and that the three available vaccines have HPV16, all of them will be suitable for vaccination programs; the price of the vaccines will be probably the main determinant to choose the vaccine.
Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Papiloma , Infecções por Papillomavirus , Neoplasias Penianas , Lesões Pré-Cancerosas , Neoplasias Cutâneas , Masculino , Humanos , Neoplasias Penianas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Carcinoma in Situ/patologia , Estudos Transversais , Estudos Retrospectivos , Carcinoma de Células Escamosas/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Neoplasias Cutâneas/complicações , Genótipo , Papillomaviridae/genéticaRESUMO
INTRODUCTION: Urine self-sampling for human papillomavirus (HPV)-based cervical cancer screening is a non-invasive method that offers several logistical advantages and high acceptability, reducing barriers related to low screening coverage. This study developed and evaluated the performance of a low-cost urine self-sampling method for HPV-testing and explored the acceptability and feasibility of potential implementation of this alternative in routine screening. METHODS: A series of sequential laboratory assays examined the impact of several pre-analytical conditions for obtaining DNA from urine and subsequent HPV detection. Initially, we assessed the effect of ethylaminediaminetetraacetic acid (EDTA) as a DNA preservative examining several variables including EDTA concentration, specimen storage temperature, time between urine collection and DNA extraction, and first-morning micturition versus convenience sample collection. We further evaluated the agreement of HPV-testing between urine and clinician-collected cervical samples among 95 women. Finally, we explored the costs of self-sampling supplies as well as the acceptability and feasibility of urine self-sampling among women and healthcare workers. RESULTS: Our results revealed higher DNA concentrations were obtained when using a 40mM EDTA solution, storing specimens at 25°C and extracting DNA within 72 hrs. of urine collection, regardless of using first-morning micturition or a convenience sampling. We observed good agreement (Kappa = 0.72) between urine and clinician-collected cervical samples for HPV detection. Furthermore, urine self-sampling was an affordable method (USD 1.10), well accepted among cervical cancer screening users, healthcare workers, and decision-makers. CONCLUSION: These results suggest urine self-sampling is feasible and appropriate alternative for HPV-testing in HPV-based screening programs in lower-resource contexts.
Assuntos
Alphapapillomavirus , DNA Viral , Detecção Precoce de Câncer , Infecções por Papillomavirus , Coleta de Urina , Neoplasias do Colo do Útero , Adulto , Alphapapillomavirus/genética , Alphapapillomavirus/metabolismo , Colo do Útero/metabolismo , Colo do Útero/virologia , DNA Viral/genética , DNA Viral/urina , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/urina , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/urina , Neoplasias do Colo do Útero/virologiaAssuntos
Humanos , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias do Colo do Útero/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Detecção Precoce de Câncer , Testes de DNA para Papilomavírus Humano , Promoção da Saúde/organização & administração , Avaliação de Programas e Projetos de Saúde , Esquemas de Imunização , Vacinação , Ensaios Clínicos Fase III como Assunto , /diagnóstico , América Latina/epidemiologiaAssuntos
Detecção Precoce de Câncer , Promoção da Saúde/organização & administração , Testes de DNA para Papilomavírus Humano , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Adolescente , Adulto , Criança , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Controlados como Assunto , Países em Desenvolvimento , Feminino , Humanos , Esquemas de Imunização , América Latina/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Avaliação de Programas e Projetos de Saúde , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/epidemiologia , Adulto Jovem , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/virologiaAssuntos
Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Criança , Detecção Precoce de Câncer , Feminino , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Humanos , América Latina , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/cirurgia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto JovemRESUMO
OBJECTIVE: To outline the design of a clinical trial to evaluate the impact of HPV vaccination as part of a hrHPV-based primary screening program to extend screening intervals. MATERIALS AND METHODS: A total of 18,000 women aged 25-45 years, attending the regular cervical cancer-screening program in primary health care services in Tlalpan, Mexico City, will be invited to the study. Eligible participants will be assigned to one of three comparison groups: 1) HPV16/18 vaccine and hrHPV-based screening; 2) HPV6/11/16/18 vaccine and hrHPV-based screening; 3) Control group who will receive only hrHPV-based screening. Strict surveillance of hrHPV persistent infection and occurrence of precancerous lesions will be conducted to estimate safety profiles at different screening intervals; participants will undergo diagnosis confirmation and treatment as necessary. CONCLUSION: The FASTER-Tlalpan Study will provide insights into new approaches of cervical cancer prevention programs. It will offer valuable information on potential benefits of combining HPV vaccination and hrHPV-based screening to safety extend screening intervals.
Assuntos
Ensaios Clínicos como Assunto/métodos , Detecção Precoce de Câncer , Vacinas contra Papillomavirus , Serviços Preventivos de Saúde/organização & administração , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Adulto , Feminino , Papillomavirus Humano 11/imunologia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Papillomavirus Humano 6/imunologia , Humanos , México , Pessoa de Meia-Idade , Vigilância da População , Avaliação de Programas e Projetos de Saúde , Projetos de Pesquisa , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/virologiaRESUMO
Abstract Objective: To outline the design of a clinical trial to evaluate the impact of HPV vaccination as part of a hrHPV-based primary screening program to extend screening intervals. Materials and methods: A total of 18,000 women aged 25-45 years, attending the regular cervical cancer-screening program in primary health care services in Tlalpan, Mexico City, will be invited to the study. Eligible participants will be assigned to one of three comparison groups: 1) HPV16/18 vaccine and hrHPV-based screening; 2) HPV6/11/16/18 vaccine and hrHPV-based screening; 3) Control group who will receive only hrHPV-based screening. Strict surveillance of hrHPV persistent infection and occurrence of precancerous lesions will be conducted to estimate safety profiles at different screening intervals; participants will undergo diagnosis confirmation and treatment as necessary. Conclusion: The FASTER-Tlalpan Study will provide insights into new approaches of cervical cancer prevention programs. It will offer valuable information on potential benefits of combining HPV vaccination and hrHPV-based screening to safety extend screening intervals.
Resumen Objetivo: Describir los métodos de un ensayo clínico que permita evaluar el impacto de la incorporación de la vacunación contra VPH en el programa de detección oportuna de cáncer cervical con el fin de ampliar los intervalos de tamizaje. Material y métodos: Un total de 18 000 mujeres entre 25 y 45 años, usuarias del programa de detección oportuna de cáncer cervical de la Ciudad de México en Tlalpan, serán invitadas a participar en el estudio. Las mujeres elegibles serán aleatorizadas a uno de tres grupos de comparación: 1) Vacunación contra VPH16/18 y tamizaje con VPHar; 2) Vacunación contra VPH6/11/16/18 y tamizadas con VPHar; 3) Grupo control que será sólo tamizado con VPHar. Se llevará a cabo una estrecha vigilancia de la infección persistente de VPHar y de la ocurrencia de lesiones precancerosas, con el fin de estimar el perfil de seguridad de intervalos de tamizaje de distinta duración. Todas las participantes contarán con procedimientos de confirmación diagnóstica y tratamiento en caso necesario. Conclusión: El estudio FASTER-Tlalpan introducirá una nueva visión de la implementación de nuevos abordajes en la prevención de cáncer cervical. Ofrecerá información de los potenciales beneficios de la combinación de la vacunación contra VPH y el tamizaje basado en VPHar para extender los intervalos de tamizaje.
Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Serviços Preventivos de Saúde/organização & administração , Neoplasias do Colo do Útero/prevenção & controle , Ensaios Clínicos como Assunto/métodos , Vacinação , Vacinas contra Papillomavirus , Detecção Precoce de Câncer , Avaliação de Programas e Projetos de Saúde , /diagnóstico , Papillomavirus Humano 11/imunologia , MéxicoAssuntos
Humanos , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias do Colo do Útero/prevenção & controle , Lesões Pré-Cancerosas/diagnóstico , Esfregaço Vaginal , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Programas de Rastreamento/organização & administração , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Detecção Precoce de Câncer , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , América LatinaRESUMO
UNLABELLED: Aim To estimate relative contribution and time trends of HPV types in cervical cancer in Cali, Colombia over a 50 years' period. METHODS: Paraffin blocks of 736 cervical cancer histological confirmed cases were retrieved from the pathology laboratory at Hospital Universitario del Valle (Cali, Colombia) and HPV genotyped using SPF10-PCR/DEIA/LiPA25 (version 1) assay. Marginal effect of age and year of diagnosis in secular trends of HPV type prevalence among HPV+ cases were assessed by robust Poisson regression analysis. RESULTS: 64.7% (95%CI: 59.9-69.2) of squamous cell carcinomas (SCCs) were attributed to HPV 16 and 18, 78.2% (95%CI: 74-82) to HPV 16, 18, 31, 33 and 45 and 84.8% (95%CI: 81-88.1) to HPV 16, 18, 31, 33, 45, 52 and 58 while ninety-three percent of adenocarcinomas (ADCs) were attributed to HPV 16, 18 and 45 only. The prevalence of specific HPV types did not change over the 50-year period. A significant downward trend of prevalence ratios of HPV16 (âP=0.017) and α7 but HPV 18 (i.e., HPV 39, 45, 68, 70, âP=0.024) with increasing age at diagnosis was observed. In contrast, the prevalence ratio to other HPV genotypes of α9 but HPV 16 genotypes (i.e., HPV 31, 33, 35, 52, 58, 67, âP=0.002) increased with increasing age at diagnosis. CONCLUSION: No changes were observed in the relative contribution of HPV types in cervical cancer in Cali, Colombia during the 50 years. In this population, an HPV vaccine including the HPV 16, 18, 31, 33, 45, 52 and 58 genotypes may have the potential to prevent â¼85% and 93% of SCC and ADC cases respectively.
Assuntos
Adenocarcinoma/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adenocarcinoma/virologia , Adulto , Idoso , Carcinoma de Células Escamosas/virologia , Colômbia/epidemiologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Papillomaviridae/classificação , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Prevalência , Fatores de Tempo , Neoplasias do Colo do Útero/virologiaRESUMO
BACKGROUND: There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received. METHODS: Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase. FINDINGS: We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22â327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7-79·1), two doses was 76·0% (62·0-85·3), and one dose was 85·7% (70·7-93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0-63·0), two doses was 37·7% (12·4-55·9), and one dose was 36·6% (-5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2-87·5) and 82·6% (42·3-96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0-87·0; CVT data only), but not those receiving it at one month (10·1%, -42·0 to 43·3), was similar to the three-dose group. INTERPRETATION: 4 years after vaccination of women aged 15-25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine. FUNDING: US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA).