RESUMO
Hereditary breast and ovarian cancer syndrome is caused by germline mutations in BRCA1/2 genes. These genes are very large and their mutations are heterogeneous and scattered throughout the coding sequence. In addition to the above-mentioned mutations, variants of uncertain/unknown significance (VUSs) have been identified in BRCA genes, which make more difficult the clinical management of the patient and risk assessment. In the last decades, several laboratories have developed different databases that contain more than 2000 variants for the two genes and integrated strategies which include multifactorial prediction models based on direct and indirect genetic evidence, to classify the VUSs and attribute them a clinical significance associated with a deleterious, high/low or neutral risk. This review provides a comprehensive overview of literature studies concerning the VUSs, in order to assess their impact on the population and provide new insight useful for the appropriate patient management in clinical practice.
Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Síndrome Hereditária de Câncer de Mama e Ovário , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Mutação , Neoplasias Ovarianas/genética , Medição de RiscoRESUMO
OBJECTIVE: The aim of this study was to introduce the VaccinaTion & Hpv Knowledge (THinK) questionnaire to assess knowledge about human papillomavirus (HPV) and attitude to HPV-vaccination. Its reliability and validity was demonstrated in a sample of women living in Sicily (southern Italy). METHODS: A cross-sectional survey was conducted on a sample of 220 women at the "Paolo Giaccone" University Hospital in Palermo (Sicily), aged 18-61. Data were analyzed through Cronbach's alpha and exploratory factor analysis, followed by a structural equation model with measurement component. The two-level data structure was explicitly considered. RESULTS: Three dimensions were found: "knowledge of HPV infection (kHPV), "Attitude to be vaccinated against HPV (aHPV)" and "Knowledge about vaccines (KV)" (97% overall explained variance). Internal consistency was good for the whole questionnaire (0.82) and the first dimension (0.88) and acceptable for the second (0.78) and the third dimension (0.73). 23% of women showed no or little knowledge of HPV and 44.3% of women had no or little knowledge about HPV induced lesions. DISCUSSION: The use of a validated questionnaire may serve as a useful measure to assess general knowledge about HPV and attitude towards vaccination against HPV in the primary prevention setting.
RESUMO
While bivalent and quadrivalent HPV vaccines have been used for about 10 years, a nonavalent vaccine against HPV types 6/11/16/18/31/33/45/52 and 58 has been recently approved by FDA and EMA and is now commercially available. The objective of our study was to evaluate the potential impact of the nonavalent vaccine on HPV infection and related low- and high-grade squamous intraepithelial lesions (LSIL, HSIL), compared to the impact of the quadrivalent vaccine, in a female population living in Sicily (Italy). Low estimates of HPV vaccine impact were calculated as prevalence of HPV 6/11/16/18/31/33/45/52 and 58 genotypes, alone or in association, but excluding presence of other HPV types; high estimates were calculated as prevalence of HPV 6/11/16/18/31/33/45/52 and 58 genotypes alone or in association, in the presence of other HPV types. The nonavalent HPV vaccine showed increased impact, compared to the quadrivalent vaccine. Estimates of potential impact varied from 30.9% (low estimate) to 53.3% (high estimate) for LSIL, and from 56.9% to 81,0% for HSIL. The proportion of additional cases potentially prevented by the nonavalent vaccine was 14.4%-23.8% for LSIL, and 19.0%-32.8% for HSIL. The benefit of the nonavalent vaccine compared to the quadrivalent vaccine was more than 80% for both low and high impact estimates for LSIL and more than 50% for both low and high impact estimates for HSIL. The present study confirms that the switch from a first generation HPV vaccines to a nonavalent vaccine would increase the prevention of cervical HSIL in up to 90% of cases.