RESUMO
OBJECTIVE: To evaluate partial HPV16/18 genotyping as a possible biomarker to select women attending HPV-based cervical cancer screening at higher risk to be referred to colposcopy. DESIGN: Population-based cohort study. SETTING: Organised cervical cancer screening programmes (Italy). POPULATION: Women with high-risk HPV infection (period: 2015-2019). METHODS: We analysed the association between partial HPV16/18 genotyping, cytology triage and histologically confirmed diagnosis of high-grade cervical intraepithelial neoplasia (CIN3+ ) lesions. MAIN OUTCOME MEASURES: Detection rate (DR) and positive predictive value (PPV) for histologically confirmed CIN3+ (any episode in the 2 years after baseline); sensitivity for CIN3+ and number of colposcopies needed for lesion detection. RESULTS: The study included 145 437 women screened with HPV testing by the clinically validated COBAS 4800 HPV assay (Roche). Overall, 9601 (6.6%) women were HPV+ at baseline; HPV16 and HPV18 were present in 1865 and 594 samples, respectively. The cumulative (baseline plus 1-year repeat) cytology positivity was 42.8% and high-grade cytology was significantly higher (P < 0.0001) among women with HPV16 infection at baseline (15.2%). The cumulative CIN3+ DR for women with HPV16, HPV18 and other HPV-type infections was 9.8%, 3.4% and 1.8%, respectively. CONCLUSIONS: Partial HPV16 genotyping may play a role in triage, whereas HPV18 seems to behave much more similarly to the other HPV types and does not provide additional stratification. HPV16 genotyping combined with high-grade cytology can be envisaged as a triage biomarker in cervical screening to maximise CIN3+ detection while minimising colposcopy at baseline or 1-year repeat. TWEETABLE ABSTRACT: HPV16 genotyping combined with high-grade cytology can be used as triage biomarker for CIN3+ in HPV-positive women.
Assuntos
Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Adulto , Idade de Início , Biomarcadores Tumorais , Colposcopia , Detecção Precoce de Câncer , Feminino , Técnicas Histológicas , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Itália/epidemiologia , Programas de Rastreamento , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Gravidez , Fatores de Risco , Esfregaço Vaginal , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
OBJECTIVE: To assess the 5-year risk of high-grade lesions in women with a transient high-risk HPV infection. DESIGN: Population-based cohort study. SETTING: HPV primary testing within population-based organised cervical cancer screening programmes. POPULATION: Italian women enrolled in seven pilot projects and attending the second round. METHODS: On the basis of the cytology triage performed on HPV-positive women, immediate colposcopy or HPV repeat at 12 months was recommended. Data were collected at the subsequent round 3-4 years after HPV infection clearance. MAIN OUTCOME MEASURES: Rates of HPV infection, CIN2+ and CIN3+ detection at subsequent round after HPV clearance, and relative risks (RR) in comparison with HPV-negative women (with 95% confidence interval). RESULTS: Data on 1230 women (1027 aged 25-64 years and 203 aged 35-64 years) have been analysed. Overall compliance with repeat HPV testing was 84%. In comparison with HPV-negative women, those with a transient HPV infection had higher proportions of HPV positivity (15% versus 3.7%) and of CIN2+ lesions (0.87% versus 0.23%) in round two; most of these (7/10) were CIN2; no cancers were detected, and CIN3 occurred in 3/1230 (0.24%). CONCLUSIONS: HPV-based protocols for cervical cancer screening allow long intervals for HPV-negative women; it is important to monitor the clinical outcome in the women with transient high-risk HPV infection. CIN3 detection is similar to that observed in routine European cytology-based screening programmes (CIN3+: 2.7); 5-year intervals may provide reasonable protection but longer intervals are not recommended. TWEETABLE ABSTRACT: A screening interval of 5 years (but no longer) appears safe in women with transient HPV detection.
Assuntos
Detecção Precoce de Câncer , Infecções por Papillomavirus/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/estatística & dados numéricos , Adulto , Estudos de Coortes , Colposcopia , Feminino , Humanos , Itália/epidemiologia , Metanálise como Assunto , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Projetos Piloto , Medição de Risco , Fatores de Tempo , Neoplasias do Colo do Útero/epidemiologia , Displasia do Colo do Útero/epidemiologiaRESUMO
OBJECTIVE: To compare the results from an initial negative human papillomavirus (HPV) test with re-screening after 3 years in women attending two HPV-based screening programmes. DESIGN: Population-based cohort study. SETTING: Two cervical service screening programmes in Italy. POPULATION: Women aged 25-64 years invited to screening from April 2009 to October 2015. METHODS: Eligible women were invited to undergo an HPV test. Those with a negative HPV test went on to the next screening round 3 years later. Cytology triage was performed for HPV+ (HPV by Hybrid Capture 2) samples, with immediate colposcopy (if abnormal) and HPV re-testing 1 year later (if negative). MAIN OUTCOME MEASURES: Participation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ (CIN2+) at colposcopy, and detection rate for CIN2+. RESULTS: We present the results from 48 751 women at the first screening and 22 000 women at re-screening 3 years later. The response rate was slightly higher at the second screening (74.5 versus 72.1% at the first screening; referral rate, RR 1.11; 95% confidence interval, 95% CI, 1.07-1.14). Compared with the first screening, we observed a significant reduction at the second screening in terms of HPV positivity (RR 0.55, 95% CI 0.51-0.60), referral rate to colposcopy (RR 0.47, 95% CI 0.41-0.53), CIN2+ detection rate (RR 0.24, 95% CI 0.13-0.39), and positive predictive value (PPV) for CIN2+ at colposcopy (RR 0.51, 95% CI 0.29-0.87). CONCLUSIONS: The very low frequency of disease and inadequate PPV at colposcopy indicate that a 3-year interval after a negative HPV test is too short. TWEETABLE ABSTRACT: Three years after a negative HPV the frequency of cervical disease is so low that re-screening is inefficient.
Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Infecções por Papillomavirus/diagnóstico , Fatores de Tempo , Neoplasias do Colo do Útero/diagnóstico , Adulto , Colo do Útero/virologia , Estudos de Coortes , Colposcopia/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus/complicações , Valor Preditivo dos Testes , Encaminhamento e Consulta/estatística & dados numéricos , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/estatística & dados numéricosRESUMO
BACKGROUND: We performed a multicentre randomised controlled trial to evaluate the effect on participation in organised screening programmes of a self-sampling device mailed home or picked up at a pharmacy compared with the standard recall letter. METHODS: Women aged 30-64 non-responding to screening invitation were eligible. Response rate to first invitation ranged from 30% to 60% between centres. The control was the standard reminder letter to undergo the test used by the programme (Pap test in three centres and HPV DNA test in three other centres). Home mailing of the self-sampler was preceded by a letter with a leaflet about HPV. The analysis was intention-to-treat. RESULTS: In all, 14 041 women were randomised and recruited: 5012 in the control arm, 4516 to receive the self-sampler at home, and 4513 to pick up the self-sampler at a pharmacy. Participation was 11.9% in the control, 21.6% (relative participation: 1.75; 95% CI 1.60-1.93) in home, and 12.0% (relative participation: 0.96; 95% CI 0.86-1.07) in the pharmacy arms, respectively. The heterogeneity between centres was high (excess heterogeneity of that expected due to chance, i.e., I(2), 94.9% and 94.1% for home and pharmacy arm, respectively). The estimated impact on the overall coverage was +4.3% for home mail self-sampling compared with +2.2% for standard reminder. CONCLUSIONS: Home mailing of self-sampler proved to be an effective way to increase participation in screening programmes, even in those with HPV as primary testing. Picking up at pharmacies showed effects varying from centre to centre.
Assuntos
Detecção Precoce de Câncer/métodos , Participação do Paciente , Farmácias , Serviços Postais , Autocuidado , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/instrumentação , Adulto , Correspondência como Assunto , Coleta de Dados , Feminino , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Participação do Paciente/métodos , Participação do Paciente/estatística & dados numéricos , Manejo de Espécimes/instrumentação , Manejo de Espécimes/métodos , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal/métodosRESUMO
Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is an entity with peculiar clinical and molecular characteristics, which mainly arises from the reticulated epithelium lining the crypts of the palatine tonsils and the base of the tongue. The only head and neck site with a definite etiological association between persistent high-risk (HR) HPV infection and development of SCC is the oropharynx. HPV-positive malignancies represent 5-20% of all HNSCCs and 40-90% of those arising from the oropharynx, with widely variable rates depending on the geographic area, population, relative prevalence of environment-related SCC and detection assay. HPV-16 is by far the most common HR HPV genotype detected in oropharyngeal SCC (OPSCC), and the only definitely carcinogenic genotype for the head and neck region. Patients with HPV-induced OPSCC are more likely to be middle-aged white men, non-smokers, non-drinkers or mild to moderate drinkers, with higher socioeconomic status and better performance status than subjects with HPV-unrelated SCC. HPV-induced HNSCCs are often described as non-keratinizing, poorly differentiated or basaloid carcinomas, and are diagnosed in earlier T-category with a trend for a more advanced N-category, with cystic degeneration, than the HPV-unrelated carcinomas. HPV positivity is associated with better response to treatment and modality-independent survival benefit. Treatment selection in HPV-related oropharyngeal carcinoma is becoming a critical issue, and although there is no evidence from randomized, controlled trials to support a treatment de-escalation in HPV-positive SCC, some investigators argue that intensive combined modality strategies may represent an overtreatment.
Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/virologia , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/terapia , Sondas de DNA de HPV , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/terapia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVE: To present the results of the first 2 years of a human papillomavirus (HPV) test-based screening programme outside the research context. DESIGN: Population-based cohort study. SETTING: A cervical service screening programme in Italy. POPULATION: Women aged 25-64 years invited to screening from April 2009 to April 2011. METHODS: Eligible women were invited to undergo an HPV test: those with a negative HPV test went on to the next screening episode; those with a positive HPV went on to triage with a Pap smear. Women with positive cytology (i.e. positive for atypical squamous cells of undetermined significance or worse, ASC-US+) were referred to colposcopy, whereas those with negative cytology were referred to repeat HPV testing 1 year later. MAIN OUTCOME MEASURES: Participation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ (CIN2+) at colposcopy, and detection rate for CIN2+. RESULTS: Participation increased compared with the previous Pap programme (60.6 versus 43.9%). The HPV positivity rate was 7.0; 39.6% of Pap smears were scored as positive, and therefore 2.8% of the women screened were referred for immediate colposcopy. The compliance of women who scored positive for HPV and negative for Pap for repeat HPV testing at 12 months was 78.6%, and the HPV positivity rate was 56.6%. The overall referral rate to colposcopy was 4.6%. The overall detection rate for CIN2+ was 4.5 versus 1.5% of the Pap programme (25-34 years, 8.2%; 35+ years, 3.6%). CONCLUSIONS: Compared with the traditional Pap test, the HPV programme recorded a higher response to invitation and an increased DR for CIN2+. The most critical aspects were the reading of cytology in women that were positive for HPV and the increased workload at colposcopy.
Assuntos
Colo do Útero/virologia , DNA Viral/análise , Detecção Precoce de Câncer/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Estudos de Coortes , Colposcopia/estatística & dados numéricos , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Cooperação do Paciente , Valor Preditivo dos Testes , Encaminhamento e Consulta/estatística & dados numéricos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/estatística & dados numéricos , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND: Factors that favour a small proportion of HPV16 infections to progress to cancer are still poorly understood, but several studies have implicated a role of HPV16 genetic variation. METHODS: To evaluate the association between HPV16 genetic variants and cervical cancer risk, we designed a multicentre case-control study based on HPV16-positive cervical samples (1121 cervical cancer cases and 400 controls) from the International Agency for Research on Cancer biobank. By sequencing the E6 gene, HPV16 isolates were classified into variant lineages and the European (EUR)-lineage isolates were subclassified by the common polymorphism T350G. RESULTS: Incidence of variant lineages differed between cases and controls in Europe/Central Asia (P=0.006, driven by an underrepresentation of African lineages in cases), and South/Central America (P=0.056, driven by an overrepresentation of Asian American/North American lineages in cases). EUR-350G isolates were significantly underrepresented in cervical cancer in East Asia (odds ratio (OR)=0.02 vs EUR-350T; 95% confidence interval (CI)=0.00-0.37) and Europe/Central Asia (OR=0.42; 95% CI=0.27-0.64), whereas the opposite was true in South/Central America (OR=4.69; 95% CI=2.07-10.66). CONCLUSION: We observed that the distribution of HPV16 variants worldwide, and their relative risks for cervical cancer appear to be population-dependent.
Assuntos
Variação Genética , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/epidemiologia , Estudos de Casos e Controles , DNA Viral , Feminino , Humanos , Infecções por Papillomavirus/epidemiologia , Polimorfismo Genético , Vigilância da População , RiscoRESUMO
OBJECTIVE: To evaluate the clinical course of extensive anal condylomatosis in relation to treatment modalities, patient comorbidity and immune function, and associated papillomavirus (HPV) sequences. METHOD: Clinical data, treatment modalities and follow-up were recorded and analysed in relation to host and viral type. Histology, immunohistochemistry and molecular analyses for HPV search and typing were performed on formalin-fixed paraffin-embedded samples. RESULTS: Sixteen patients [14 males, median age 41.8 years (range 19-66)] affected by extensive anal condylomatosis [10 Buschke-Lowenstein Tumors (BLT) and 6 condylomatosis] treated in three different Italian institutions were included. There was associated preoperative anal intraepithelial neoplasia grade 3 (AIN3) in one and invasive carcinoma in three patients. After radical resection (n = 16) recurrence occurred in 4/10 (40%) BLT patients. Malignancy before or after treatment developed in 5/16 (31.25%) patients. HPV sequences were present in all the samples of 15 evaluable patients (types 6 or 11, 9 patients; type 16, 6 patients). A statistically significant association was found between presence of HPV type 16 and both malignancy and recurrence. Viral variant L83V was present in 3/4 HPV 16 positive recurrent cases. CONCLUSION: Radical resection resulted in a favourable clinical course. Typing of HPV sequences in the management of patients affected by extensive anal condylomatosis may be useful.
Assuntos
Colectomia/métodos , Condiloma Acuminado/virologia , DNA Viral/análise , HIV/genética , Vírus de Hepatite/genética , Proctite/virologia , Adulto , Idoso , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/cirurgia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Proctite/diagnóstico , Proctite/cirurgia , Prognóstico , Estudos Retrospectivos , Adulto JovemAssuntos
Aberrações Cromossômicas , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Análise Citogenética , Rearranjo Gênico/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , TrombocitoseRESUMO
Human papillomavirus (HPV) infection of the lower genital tract is now considered the most important factor in the initiation of neoplasia. Human immunodeficiency virus (HIV) infection appears to alter the natural history of HPV-associated oncogenesis, but its impact on gynaecology has only recently been defined; the Centers for Disease Control (CDC) designated moderate and severe cervical dysplasia as a category B defining condition, and invasive cervical cancer as a category C defining condition of AIDS in 1993. Anal HPV infection and anal squamous intra-epithelial lesions have been found to be highly prevalent among HIV-positive homosexual men, and recent preliminary data suggest a relatively high prevalence among HIV-positive women as well. Moreover, HPV infection and associated lesions are also observed in body sites other than the anogenital area, particularly the skin and the oral cavity.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/virologia , Neoplasias dos Genitais Femininos/virologia , Neoplasias dos Genitais Masculinos/virologia , Papillomaviridae , Infecções Tumorais por Vírus/complicações , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
Anogenital condylomata acuminata are the most frequent clinical manifestation of genital human papillomavirus (HPV) infection. Association between human immunodeficiency virus (HIV) and HPV infections is frequent (range: 26-60% in males). Topical cidofovir (a nucleotide analogue antiviral drug active against a broad range of DNA viruses) is a potential treatment for anogenital warts in immunocompromised patients. We treated three HIV-infected patients with HPV perianal condylomas with topical 1% cidofovir in flexible collodion once a day for 2 weeks. The treatment resulted in complete clearance of the HPV lesions. The patients experienced mild transient erythema without any other side-effects. None of the patients relapsed during the 10-14-month follow-up period.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antivirais/administração & dosagem , Condiloma Acuminado/tratamento farmacológico , Citosina/administração & dosagem , Organofosfonatos , Compostos Organofosforados/administração & dosagem , Dermatopatias Virais/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Administração Tópica , Adulto , Cidofovir , Condiloma Acuminado/diagnóstico , Citosina/análogos & derivados , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Recidiva , Índice de Gravidade de Doença , Dermatopatias Virais/diagnóstico , Resultado do TratamentoRESUMO
OBJECTIVE: We evaluated the prevalence of genital human papillomavirus (HPV) types in correlation with cytomorphological findings in patients at different risk for cervical intraepithelial neoplasia living in northeast Italy. METHODS: Exfoliated cervicovaginal cells from 943 women, who were divided into three groups, were analyzed by polymerase chain reaction. RESULTS: Overall, HPV prevalence rates were 7%, 38%, and 52%, respectively. The single most frequent type was HPV 16 (18%), followed by types 6, 31, 53, 58, 61, and novel/unidentified (5-7%); other types had a frequency <5%. Infection with multiple types was present in 12%. In HIV-infected women, HPV infection was correlated with lower CD4 level and higher viral load; HGSILs were correlated only with a lower CD4 count, and no correlations were found for LGSILs. CONCLUSIONS: HGSILs were associated with high-risk types, mainly HPV 16 (40%). LGSILs, instead, were associated with a broad spectrum of low-risk and high-risk types.
RESUMO
We report the first case of a girl with vertically acquired human immunodeficiency virus (HIV) infection, who developed invasive squamous cell carcinoma of the vulva at 12 years of age. Lesions resembling bowenoid papulosis covered the perianal area as well. She underwent a nonmutilating surgical excision of the infiltrating lesion. More than 3 years later, her clinical condition is excellent, although dysplastic, noninfiltrating multifocal lesions persist. This case highlights the need to perform careful periodic genital examinations in all HIV-infected children and adolescents born to HIV-positive mothers.
Assuntos
Carcinoma de Células Escamosas/etiologia , Infecções por HIV/complicações , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Neoplasias Vulvares/etiologia , Contagem de Linfócito CD4 , Carcinoma in Situ/etiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Criança , Progressão da Doença , Feminino , Infecções por HIV/transmissão , HIV-1/genética , Humanos , Estadiamento de Neoplasias , Papillomaviridae/isolamento & purificação , RNA Viral/sangue , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgiaAssuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Anticorpos Anti-HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Soronegatividade para HIV , HIV-1/imunologia , HIV-1/isolamento & purificação , Complicações Infecciosas na Gravidez/virologia , Formação de Anticorpos , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/transmissão , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Lamivudina/uso terapêutico , Nelfinavir/uso terapêutico , Gravidez , Viremia/diagnóstico , Viremia/imunologia , Zidovudina/uso terapêuticoRESUMO
In this study we examined the incidence of colposcopic-colpocytologic findings and analyzed Human Papilloma Virus (HPV)-DNA testing by Polymerase Chain Reaction (PCR) in 104 Human Immunodeficiency Virus (HIV) serous positive women (Group 1) and 218 HIV-negative women (control Groups 2 and 3). The aim of the study was to evaluate the most appropriate and efficacious diagnostic methods for screening programs for cervical cancer in HIV-positive women. For Group 1 we also considered the value of CD4+ T-lymphocytes and morphologic and molecular follow-up from 3 to 6 months. The results showed that the abnormal transformation zone (ANTZ) was present in 66.3% of the cases in Group 1 compared with 31.4% in control-Group 2 (p<0.001), and with 58.93% of the cases in control-Group 3 (p=0.257); intraepithelial squamous lesions (SIL) were found in 50% vs 5.66% (p<0.001) and vs 56.25% of the cases (p=0.433), respectively. In 28.85% of the HIV-positive patients the first cytological screening exam was not evaluable due to inflammation but in 56.67% of the cases colposcopy revealed ANTZ. The subsequent colpocytological checkup after therapy showed 10 cases (30%) of low risk squamous intraepithelial lesions (LSIL) and two cases (6.6%) of high risk squamous intraepithelial lesions (HSIL). HPV-DNA testing by PCR was positive in 53.8% of the cases in Group 1, in 6.6% in control-Group 2 and in 42% in control-Group 3. In HIV-positive patients multiple HPV genotypes were simultaneously present in 21.43% of the cases and high risk genotypes were present in 70% of the cases of HSIL. In Group 1, 36.61% of the cases had lesions of the lower genital tract. The value of CD4+ T-lympocytes was <200 cells/ml in 30% of the cases of HSIL. Our data, like those of other Authors, confirm a high incidence of HSIL, abnormal colposcopic findings, and HPV infections in HIV-positive women with respect to control-Group 2, while there was not much difference between Group 1 and control-Group 3. Such frequency again suggests that an integrated morphological diagnostic approach with colposcopy-colpocytology in the screening of immunosuppressed subjects would be worthwhile.
Assuntos
Colo do Útero/patologia , Colposcopia/métodos , DNA Viral/análise , Soropositividade para HIV , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Adulto , Carcinoma/diagnóstico , Colo do Útero/citologia , Comorbidade , Feminino , Seguimentos , Soronegatividade para HIV , Soropositividade para HIV/epidemiologia , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Reação em Cadeia da Polimerase , Medição de Risco , Sensibilidade e Especificidade , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/prevenção & controle , Neoplasias do Colo do Útero/diagnósticoRESUMO
A primary cutaneous form of peripheral T-cell lymphoma (PTCL) and a low grade B-cell non-Hodgkin's lymphoma that was classified as a variant of hairy cell leukemia (HCL) were simultaneously diagnosed in a 79-year-old woman by both phenotypic and genotypic analyses. The coexistence of a T- and B-cell lymphoma in the same patient is rare, and, to our knowledge, this particular association has not been previously described. The patient was referred to our Department for evaluation of multiple cutaneous itchy, reddish plaques; laboratory analyses disclosed a lymphocytosis, that presented 6 years earlier. A bone marrow aspirate showed a 50% B-cell interstitial infiltrate, while a skin biopsy surprisingly revealed a PTCL. Clonality of both neoplastic processes was assessed by Southern blot analysis. The indolent clinical course of the cutaneous disease, and the low and stable number of circulating neoplastic T cells supported the diagnosis of a mycosis fungoides (MF)-like PTCL. Possible oncogenic events and/or putative underlying viral infections which could have played a role in the occurrence of B- and T-cell non-Hodgkin's lymphomas in the same patient are discussed.
Assuntos
Leucemia de Células B/complicações , Leucemia de Células Pilosas/complicações , Linfoma Cutâneo de Células T/complicações , Neoplasias Cutâneas/complicações , Idoso , Biópsia , Southern Blotting , Medula Óssea/patologia , DNA/sangue , Feminino , Humanos , Imunofenotipagem , Pele/patologiaAssuntos
Genes p53/genética , Papillomaviridae , Infecções por Papillomavirus/complicações , Polimorfismo Genético , Infecções Tumorais por Vírus/complicações , Neoplasias do Colo do Útero/genética , Arginina/genética , Estudos de Casos e Controles , Divisão Celular/genética , Códon , Feminino , Predisposição Genética para Doença/genética , Predisposição Genética para Doença/virologia , Humanos , Neoplasias do Colo do Útero/virologiaRESUMO
BACKGROUND: The p27Kip1 protein regulates the G1 to S phase transition of cell cycle by binding to and inhibiting the cyclin E/Cdk2 complex. This study explores the prognostic significance of the absence of the p27Kip1 protein in patients with colorectal cancer (CRC). METHODS: Formalin-fixed tumor sections from 124 patients who underwent curative resection for stage I-III CRC were analyzed by immunohistochemistry using MoAb anti-p27KiP1. RESULTS: Detectable levels of p27Kip1 protein were found in 86% of tumors. Median follow-up was 55 months. Actuarial 5-year disease-free survival (DFS) and overall survival (OS) were 76% and 85%, respectively, in patients with tumors with p27Kip1 protein expression and 34% and 40%, respectively, in those whose tumors lacked p27Kip1 protein expression (P < .001). At multivariate analysis, tumor stage (III vs. I-II) and p27Kip1 protein status (absence vs. presence) were found to be independent prognostic factors for DFS and OS. CONCLUSIONS: Lack of p27KiP1 protein expression in CRC is a negative prognostic marker and may therefore be useful in selecting early-stage patients more likely to benefit from adjuvant treatment.
Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais , Proteínas de Ciclo Celular , Neoplasias Colorretais/diagnóstico , Quinases Ciclina-Dependentes/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos , Proteínas Supressoras de Tumor , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Inibidor de Quinase Dependente de Ciclina p27 , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Resultado do TratamentoRESUMO
Human immunodeficiency virus type 1 (HIV-1)-infected patients develop a spectrum of lymphoproliferative disorders ranging from nonneoplastic lymphadenopathies to B-cell lymphomas. Although evidence suggests that Epstein-Barr virus (EBV) might be involved, its molecular profile and expression pattern in HIV-1-related lymphoproliferations remain to be defined. Using polymerase chain reaction-based techniques, we studied EBV types and variants in 28 lymphadenopathy lesions and in 20 lymphomas (15 large cell and 5 Burkitt-like). EBV was detected in 89% of lymphadenopathies and in 80% of lymphomas; viral DNA content was significantly higher in the latter. EBNA2 and LMP1 gene analysis indicated that half of the EBV+ lymphadenopathies were coinfected with both EBV type 1 and 2 strains and/or multiple type 1 variants. Conversely, all but one lymphoma carried a single viral variant, consistently type 1 in large cell lymphomas, and type 2 in Burkitt-like tumors. Most lymphomas, but no lymphadenopathies, showed monoclonal Ig heavy-chain rearrangement. Analysis of 5 large cell lymphomas and 9 lymphadenopathies for EBV transcripts identified LMP1 mRNA in most samples, and the EBNA2 transcript in all tumors. These findings provide evidence of a heterogeneous EBV population in lymphadenopathy lesions, strengthen the notion that lymphomas arise from clonal expansion of EBV+ cells, and suggest different roles for EBV types 1 and 2 in HIV-1-related lymphoproliferations.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/virologia , HIV-1 , Herpesvirus Humano 4/isolamento & purificação , Linfonodos/virologia , Linfoma Relacionado a AIDS/virologia , DNA Viral/análise , Humanos , Linfonodos/patologia , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND/AIMS: Post-transplant lymphoproliferative disease, a potential complication of solid organ transplantation, occurs in about 3% of orthotopic liver transplant recipients. We report the genetic and virological characterization of two cases of post-transplant lymphoproliferative disease that occurred early (4 and 6 months) after orthotopic liver transplant as large-cell non-Hodgkin's lymphomas located at the hepatic hilum. METHODS: Lymphomatous tissues were analyzed for clonality and presence of Epstein-Barr virus (EBV) sequences by Southern blot, polymerase chain reaction, and in situ hybridization techniques. RESULTS: The tumors in both cases were sustained by a clonal proliferation of B lymphocytes containing type A EBV DNA. Moreover, in situ hybridization with a digoxigenin-labeled EBV-specific probe evidenced a strong nuclear signal in most of the neoplastic cells. DNA microsatellite analysis at three different loci detected alleles of donor origin in both tumor samples, suggesting that the neoplastic B cells were of donor origin. CONCLUSIONS: EBV-infected donor B lymphocytes might be responsible for intragraft post-transplant lymphoproliferative disease in orthotopic liver transplant recipients. As 20 to 30% of post-transplant lymphomas involve the graft itself, donor-derived post-transplant lymphoproliferative disease might be more frequent than presently appreciated. Prospective studies are needed to assess its real incidence and identify possible risk factors.