RESUMO
BACKGROUND: First aim was to compare ddPCR assays of ctHPVDNA with p16 IHC and qualitative HPV PCR. Second aim was to carry out longitudinal blood sampling to test for association of ctHPVDNA with histological confirmed recurrence. Third aim was to perform a multidimensional assessment which included: (1) clinical features; (2) ctHPVDNA; (3) MRI-based tumor size measurements of primary tumor (PT) and cervical lymph node metastases (CLNM). METHODS: Plasma samples were collected before treatment and during follow-up, and ddPCR assay comprising E6 of HPV16 and HPV 33 and HPV 35 was used. RESULTS: Present study was conducted at diagnosis in 117 patients and revealed a ctHPVDNA sensitivity of 100% (95% CI 95.5-100) and a specificity of 94.4 (95% CI 81.3-99.3), positive predictive value (PPV) of 94.4 (95% CI 81.3-99.3), and negative predictive value (NPP) of 100% (95% CI 89.7-100). During follow-up ctHPVDNA had a sensitivity of 100% (95% CI 72.1-100)% and specificity of 98.4% (95% CI 91.7-100)%, PPV% of 90.9% (95% CI 62.3-98.4) and NPV% of 100% (95% CI 94.3-100) for ability to detect recurrence. Correlation between both the CLNM volume and the sum of PT and CLNM volume was observed. CONCLUSIONS: ctHPVDNA was superior to p16 in identification of HPV-OPSCC at diagnosis. Introduction of ctHPVDNA, beyond diagnostic setting, represents a great opportunity to improve follow-up protocol of OPSCC patients.
Assuntos
Imageamento por Ressonância Magnética , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Feminino , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/sangue , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Imageamento por Ressonância Magnética/métodos , Idoso , DNA Viral/sangue , DNA Tumoral Circulante/sangue , Sensibilidade e Especificidade , Adulto , Recidiva Local de Neoplasia/virologia , Metástase Linfática , Reação em Cadeia da Polimerase , Valor Preditivo dos TestesRESUMO
BACKGROUND: Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping. METHODS: Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance. FINDINGS: Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting. INTERPRETATION: Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years. FUNDING: Italian Ministry of Health (grant number RF-2009-1536040). Hologic-Genprobe, Roche Diagnostics, and Becton & Dickinson provided financial and non-financial support.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina , Genótipo , Antígeno Ki-67 , Infecções por Papillomavirus , Humanos , Feminino , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Adulto , Itália/epidemiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Pessoa de Meia-Idade , Triagem/métodos , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/genética , Papillomaviridae/genética , DNA Viral/genética , Colposcopia , Técnicas de Genotipagem/métodos , Coloração e Rotulagem/métodos , Estudos Retrospectivos , Detecção Precoce de Câncer/métodos , CitologiaRESUMO
BACKGROUND: Anal cytology represents a tool for anal cancer screening in high-risk populations. In addition to accuracy, the reproducibility of the interpretation is of key importance. The authors evaluated the agreement of anal cytologic interpretation between two cytopathologists. METHODS: Liquid-based cytologic slides from human immunodeficiency virus (HIV)-negative men who have sex with men (MSM) were evaluated by two readers with at least 10 years of expertise in cervical cytology. Cases with a discordant interpretation were reviewed, and a consensus was reached. Human papillomavirus (HPV) genotyping was performed using a proprietary HPV genotyping test. Unweighted and weighted Cohen kappa and 95% confidence interval (CI) values were calculated. RESULTS: Overall, 713 slides that were adequate for interpretation were evaluated (MSM: median age, 33 years). An HPV test was performed on 620 samples (87.0%). Considering a dichotomous interpretation (negative for intraepithelial lesion or malignancy vs. atypical squamous cells of undetermined significance or worse), the crude agreement between the two readers was 93.3% (kappa = 0.82; 95% CI, 0.77-0.87). Once a consensus for discordant cases was reached, the best agreement was found for the negative for intraepithelial lesion or malignancy category (511 of 528 samples; 96.8%), whereas the atypical squamous cells of undetermined significance category showed the lowest agreement (90 of 117 samples, 76.9%). Considering the individual cytologic categories, overall agreement was 92.1% (kappa = 0.85; 95% CI, 0.81-0.89). The discordant interpretations were not associated with high-risk HPV infection, HPV16 infection, or MSM age. CONCLUSIONS: The results indicating excellent interobserver agreement in this study substantiate the use of anal cytology in the setting of human immunodeficiency virus-negative MSM.
Assuntos
Neoplasias do Ânus , Citodiagnóstico , Homossexualidade Masculina , Variações Dependentes do Observador , Infecções por Papillomavirus , Humanos , Masculino , Neoplasias do Ânus/virologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/diagnóstico , Adulto , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Citodiagnóstico/métodos , Homossexualidade Masculina/estatística & dados numéricos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Papillomaviridae/genética , Canal Anal/virologia , Canal Anal/patologia , Reprodutibilidade dos Testes , Adulto Jovem , Detecção Precoce de Câncer/métodos , Idoso , CitologiaRESUMO
Locoregional recurrences represent a frequently unexpected problem in head and neck squamous cell carcinoma (HNSCC). Relapse often (10-30%) occurs in patients with histologically negative resection margins (RMs), probably due to residual tumor cells or hidden pre-cancerous lesions in normal mucosa, both missed by histopathological examination. Therefore, definition of a 'clean' or tumor-negative RM is controversial, demanding for novel approaches to be accurately explored. Here, we evaluated next generation sequencing (NGS) and digital PCR (dPCR) as tools to profile TP53 mutational status and circulating microRNA expression aiming at scoring the locoregional risk of recurrence by means of molecular analyses. Serial monitoring of these biomarkers allowed identifying patients at high risk, laying the ground for accurate tracking of disease evolution and potential intensification of post-operative treatments. Additionally, our pipeline demonstrated its applicability into the clinical routine, being cost-effective and feasible in terms of patient sampling, holding promise to accurately (re)-stage RMs in the era of precision medicine.
RESUMO
BACKGROUND: Lichen sclerosus (LS) is an inflammatory disease mostly arising at the genital level. It is unclear whether human papillomaviruses (HPVs) have an etiological significance in LS, and data on their prevalence in patients with LS are controversial. OBJECTIVES: The authors assessed alpha, beta, and gamma HPV prevalence in patients with genital LS. The association of HPV positivity with demographic and clinical factors was also investigated. METHODS: One hundred thirty-two formalin-fixed, paraffin-embedded LS samples (2016-2020) were retrieved from the archives of a pathology department. Alpha HPVs were genotyped with the INNO-LiPA HPV Genotyping Extra II kit. Beta and gamma HPVs were searched by multiplex Polymerase Chain Reaction. Immunostaining for p16 INK4a was performed on high-risk HPV-positive samples. RESULTS: Patients had a median age of 61 years, were mostly women ( n = 73, 55.3%), and with an early disease stage ( n = 79, 59.8%). Alpha HPVs were detected in 12/132 cases (9.1%). Among the 5 high-risk HPV-positive cases, only 2 displayed a strong and diffuse p16 INK4a staining. Beta genus was the most prevalent (35/132, 26.5%) and HPV5 was the most frequent beta genotype (25/132, 18.9%). There were 3 gamma HPV-positive cases among those with a valid result (3/131, 2.3%). Multiple infections with genotypes belonging to different genera were infrequent (3/131, 2.3%). No significant differences in the prevalence of the individual genera were observed according to sex and disease stage. CONCLUSIONS: Of the 3 HPV genera, beta genus showed the highest prevalence. Further research is needed to clarify whether the presence of beta HPVs in genital LS has a clinical significance.
Assuntos
Líquen Escleroso e Atrófico , Infecções por Papillomavirus , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Papillomavirus Humano , Líquen Escleroso e Atrófico/epidemiologia , Líquen Escleroso e Atrófico/complicações , Estudos Retrospectivos , Estudos Transversais , Papillomaviridae/genética , Genótipo , Genitália , DNA ViralRESUMO
INTRODUCTION: Anal cytology is used in the prevention of anal cancer, which disproportionally affects men who have sex with men (MSM). Data on the incidence of cytologic abnormalities in these individuals are scant. METHODS: MSM with baseline negative anal cytology and at least one further adequate cytology were included. Incidence rate for positive atypical squamous cells of undetermined significance (ASC-US+) was calculated. Kaplan-Meier curves were compared by log-rank test according to HIV status, baseline high-risk human papillomavirus (HPV) (high-risk HPV-negative, HPV16-positive, other high-risk HPV-positive [non-HPV16]) and high-risk HPV persistence (positive from baseline to the first ASC-US+ or last visit for those who remained cytologically negative). Cox univariate and multivariate analyses were performed. RESULTS: A total of 250 MSM were included: 52/153 (34.0%) HIV-uninfected MSM had an ASC-US+ report at follow-up (incidence: 13.1 × 100 person-years; 95% CI, 9.8-17.2); 48/97 (49.5%) HIV-infected MSM developed cytologic abnormalities (incidence: 16.0 × 100 person-years; 95% CI, 11.8-21.2). ASC-US+ incidence in HIV-uninfected and HIV-infected MSM did not differ significantly (p = .32). Kaplan-Meier curves did not differ significantly according to baseline high-risk HPV. Differences were significant between those with and without persistent high-risk HPVs, both among HIV-uninfected (p = .03) and HIV-infected MSM (p = .008). Age (adjusted hazard ratio [aHR], 0.98; 95% CI, 0.96-0.99), high-risk HPV persistence (aHR, 1.57; 95% CI, 1.02-2.39), and condomless receptive anal sex (aHR, 1.99; 95% CI, 1.31-3.03) were predictors for incident ASC-US+. CONCLUSIONS: Despite the limited number of subjects, in our study HIV-uninfected and HIV-infected MSM have a similar ASC-US+ incidence. Occurrence of ASC-US+ was significantly affected by age, high-risk HPV persistence, and condomless receptive anal sex. The assessment of HPV persistence might identify those MSM at higher risk for anal lesions.
Assuntos
Infecções por HIV , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Incidência , Fatores de Risco , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Papillomaviridae , PrevalênciaAssuntos
Alphapapillomavirus , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/patologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
As the primary screening test, E6/E7 mRNA has shown similar sensitivity for CIN3+ and lower positivity rate than the HPV DNA test. Nevertheless, the overall mRNA positivity is too high for immediate colposcopy, making a triage test necessary. The aim was to estimate the mRNA performance as a primary test with different triage strategies. All HPV DNA-positives were tested for mRNA, cytology and p16/ki67. A sample of HPV DNA-negatives was also tested for mRNA to estimate test specificity. We included all CIN3+ histologically diagnosed within 24 months since recruitment. Of the 41 127 participants, 7.7% were HPV DNA-positive, of which 66.4% were mRNA-positive. Among the HPV DNA-negatives, 10/1108 (0.9%) were mRNA-positive. Overall, 97 CIN3+ were found. If mRNA was used as the primary test, it would miss about 3% of all CIN3+ with a 22% reduction of positivity compared with HPV DNA. The weighted specificity estimate for Assuntos
Infecções por Papillomavirus
, Neoplasias do Colo do Útero
, Colposcopia
, Detecção Precoce de Câncer/métodos
, Feminino
, Humanos
, Antígeno Ki-67/genética
, Papillomaviridae/genética
, Gravidez
, RNA Mensageiro/genética
, Sensibilidade e Especificidade
, Neoplasias do Colo do Útero/diagnóstico
, Neoplasias do Colo do Útero/genética
, Neoplasias do Colo do Útero/patologia
RESUMO
HIV-infected men who have sex with men (MSM) display the highest prevalence of anal infection by high-risk Human Papillomaviruses (hrHPVs) and incidence of anal carcinoma. Anal specimens were genotyped by the Linear Array. Incidence and clearance of anal infection by hrHPVs, hrHPVs other than HPV16, low-risk HPVs, and four individual types (6,11,16,18) were estimated using a two-state Markov model. Determinants for incidence and clearance were assessed by logistic regression. Overall, 204 individuals were included (median age 42 years, IQR = 34-49). For hrHPVs, incidence and clearance rates were 36.1 × 1000 person-months (p-m) (95% CI 23.3-56.5) and 15.6 × 1000 p-m (95% CI 10.7-23.3), respectively. HPV16 showed a higher incidence than HPV18 (10.2 vs. 7.2 × 1000 p-m). Its clearance was more than twofold lower than that of HPV18 (30.1 vs. 78.2 × 1000 p-m). MSM receiving cART displayed a 68% to 88% decrease in risk of acquiring hrHPVs, hrHPVs other than HPV16, HPV16, and HPV18 (adjusted Hazard Ratio [aHR] 0.13, 95% CI 0.02-0.67; aHR 0.22, 95% CI 0.06-0.78; aHR 0.32, 95% CI 0.12-0.90; aHR 0.12, 95% CI 0.04-0.31, respectively) than patients not treated. A nadir CD4 + count < 200 cells/mm3 significantly reduced the clearance of hrHPVs other than HPV16 (aHR 0.39, 95% CI 0.17-0.90). cART use reduces the risk of acquiring anal infection by hrHPVs.
Assuntos
Canal Anal/virologia , Doenças do Ânus/epidemiologia , Coinfecção , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Infecções por Papillomavirus/epidemiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Doenças do Ânus/diagnóstico , Doenças do Ânus/prevenção & controle , Doenças do Ânus/virologia , Quimioterapia Combinada , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Prognóstico , Fatores de Proteção , Medição de Risco , Fatores de Risco , Cidade de Roma/epidemiologia , Fatores de TempoRESUMO
OBJECTIVES/HYPOTHESIS: The aim of this study was to assess the value of cell-free human papillomavirus-DNA (cfHPV-DNA) as a diagnostic test for the post-treatment surveillance of patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) through a systematic review and meta-analysis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A literature search was conducted in three databases (MEDLINE, Embase, and Scopus) in January 2021. The population included patients with HPV-positive HNSCC. The intervention was the use of the repeated liquid biopsy with circulating HPV-DNA detection during follow-up. The outcome was to establish the value of cfHPV-DNA as a diagnostic test for the post-treatment surveillance of patients with HPV-positive HNSCC. RESULTS: Ten studies included in the meta-analysis provided a total of 457 patients with HPV-positive HNSCC. The meta-analytic study estimated the diagnostic performance of cfHPV-DNA as follows: pooled sensitivity and specificity of 0.65 (95% confidence interval [CI]: 0.40-0.84) and 0.99 (99% CI: 0.96-0.99), respectively; positive and negative likelihood ratios of 62.5 (99% CI: 22.9-170.2) and 0.05 (99% CI: 0.013-0.24), respectively; and pooled diagnostic odds ratio of 371.66 (99% CI: 60.4-2286.7). CONCLUSION: Currently, the follow-up protocol for HNSCC patients includes routine clinical evaluation and radiological imaging. Biomarkers to monitor this disease are not established. Considering its high specificity, cfHPV-DNA represents a potential confirmatory test in the case of positive positron emission tomography and computed tomography. In the near future, cfHPV-DNA could be used as a biomarker for monitoring the treatment response during the clinical trials of de-escalation therapy or immunotherapy. Larger sample sizes and the homologation of study protocols and methodology are needed to better establish its utility in the clinical practice. Laryngoscope, 132:560-568, 2022.
Assuntos
Carcinoma de Células Escamosas/virologia , Ácidos Nucleicos Livres/genética , DNA Viral/genética , Neoplasias de Cabeça e Pescoço/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Biópsia Líquida , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
AIMS: The introduction of immunotherapy for patients with head and neck squamous cell carcinoma (HNSCC) raises the need for harmonisation between different types of antibody and immunohistochemistry platform for evaluating the expression of PD-L1 by use of the combined positive score (CPS) in this tumour. The aim of this study was to compare the expression of PD-L1 as determined with the CPS and two widely used assays (the 22C3 PharmDx assay and the SP263 assay) in a cohort of HNSCCs. METHODS AND RESULTS: We analysed 43 whole sections of HNSCC with two different anti-PD-L1 antibodies, 22C3 and SP263. The results, expressed as the CPS, were evaluated by 10 trained pathologists and statistical analyses were performed. We found a very similar results for PD-L1 expression between the 22C3 PharmDx assay and the SP263 assay in our cohort, and a strong and significant correlation between the two assays for all specimens (P < 0.0001). The interobserver reliability among pathologists for the continuous scores of CPS with the intraclass correlation coefficient and the correlation between the two assays were both good. Moreover, the rate of agreement between assays was high at all cut-offs and was best for the most relevant cut-off of CPS ≥ 1, and the kappa values were always in the range of almost perfect. CONCLUSIONS: Two different assays (the 22C3 PharmDx assay and SP263 assay) for PD-L1 in HNSCC showed high agreement. These data suggest that these two assays are interchangeable in the selection of patients with HNSCC for immunotherapy.
Assuntos
Antígeno B7-H1/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
How to manage human papillomavirus (HPV)-positive women in cervical cancer screening remains debated. Our study compared different strategies to triage HPV positivity in a large cohort of women participating in a population HPV-based screening program. Women were tested for HPV (Cobas 4800; Roche), and those positive were triaged with cytology; cytology-positives were referred to colposcopy, while negatives were referred to 1-year HPV retesting. All HPV-positive women were also evaluated with p16/ki67 dual staining (Roche). All lesions found within 24 months of follow-up were included in the analyses. Of the 70 146 women tested, 4757 (6.8%) were HPV-positive. Of these, 1090 were cytology-positive and were referred to colposcopy. Of the 2958 HPV-positive/cytology-negative women who presented at 1-year retesting, 1752 (59.9%) still tested positive. Cumulatively, 532 CIN2+ (including 294 CIN3+) were found. The sensitivity of cytology, HPV16/18 and p16/ki67 as triage test for CIN3+ was 67.9%, 56.0% and 85.0%, respectively. The positive predictive value (PPV) for immediate colposcopy referral was 21.0%, 15.8% and 22.9%, respectively. Combining cytology with typing increased sensitivity to 83.9% and lowered PPV to 14.8%, while combining p16/ki67 and typing increased sensitivity to 91.1%, lowering the PPV to 15.9%. Women negative to p16/ki67 triage presented a cumulative 1-year CIN3+ risk of about 1%. In conclusion, when triaging HPV positivity, p16/ki67 performed better than cytology with or without HPV16/18 genotyping. The strategies that included dual staining achieved sensitivity and low 1-year risk for CIN3+ sufficiently high enough to permit considering extending the surveillance interval to 2 to 3 years for HPV-positive/triage-negative women.
Assuntos
Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Triagem , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Feminino , Genótipo , Testes de DNA para Papilomavírus Humano , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Antígeno Ki-67/análiseRESUMO
Men who have sex with men (MSM) harbor the highest prevalence of anal and oral Human Papillomavirus (HPV) infection, particularly if HIV-infected. We investigated anal and oral HPV infections in HIV-infected and HIV-uninfected MSM, to assess concurrent (HPV detected at both sites, irrespective of the genotypes), and concordant infections (same genotype[s] detected at both sites). Matched anal and oral samples from 161 MSM (85 HIV-infected, and 76 HIV-uninfected) were tested with the Linear Array. Determinants of concurrent and concordant infections were evaluated using logistic regression. Anal infections were 4 to 7 times more frequent than oral infections in both study groups (p < 0.0001). Concurrent infections were not significantly different in HIV-infected (25.9%) and HIV-uninfected MSM (17.1%), p = 0.18. A concordant infection was found in 15 MSM (9.3%). Concordance was for one genotype in 14 individuals and for four genotypes in the remaining subject. In the overall population, only age was independently associated with a concurrent infection (AOR = 3.10, 95% CI: 1.34-7.19 for >39 vs. ≤39 years). None of the parameters of sexual behavior showed independent association with concordant infections. Among MSM, concordant anal and oral HPV infections do not seem to be explained by sexual behavior, but might derive from sequential acquisition by autoinoculation.
RESUMO
The aim of this paper is to define the pre-treatment radiological characteristics of oropharyngeal squamous cell carcinoma (OPSCC) using morphological and non-morphological magnetic resonance imaging (MRI), based on HPV status, in a single-institution cohort. In total, 100 patients affected by OPSCC were prospectively enrolled in the present study. All patients underwent 1.5T MR with standard sequences, including diffusion-weighted imaging with and intravoxel incoherent motion (IVIM-DWI) technique and a dynamic contrast-enhanced (DCE) MRI. For all patients, human papillomavirus (HPV) status was available. No statistically significant differences in the volume of primary tumors (PTs) and lymph nodes (LNs) were observed based on HPV status. When comparing the two patient groups, no significant differences were found for the PT radiologic characteristics (presence of well-defined borders, exophytic growth, ulceration, and necrosis) and LN morphology (solid/cystic/necrotic). Tumor subsite, smoking status, and alcohol intake significantly differed based on HPV status, as well as ADC and Dt values of both PTs and LNs. We detected no significant difference in DCE-MRI parameters by HPV status. Based on a multivariate logistic regression model, the combination of clinical factors, such as tumor subsite and alcohol habits, with the perfusion-free diffusion coefficient Dt of LNs, may help to accurately discriminate OPSCC by HPV status.
RESUMO
Men who have sex with men (MSM) harbor the highest risk for anal carcinoma, mainly caused by Human Papillomavirus (HPV). The use of HPV-related biomarkers in the screening for this neoplasia is still debated. We assessed the association between high-risk (hr)HPV DNA, HPV16/18 DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 with cytological abnormalities (any grade) and high-grade intraepithelial lesions (HSIL) in HIV-uninfected and HIV-infected MSM. Overall, 150 cytological samples in PreservCyt (Hologic), with a negative to HSIL report, were analyzed for hrHPV DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 using the Linear Array (Roche), Aptima (Hologic), and CINtec® PLUS (Roche) assays. In HIV-infected MSM, positivity for all the biomarkers significantly increased with the cytological grade. In both populations, the association of hrHPV E6/E7 mRNA and p16/Ki-67 positivity with HPV16 did not differ significantly compared to hrHPVs other than HPV16. In HIV-uninfected MSM, the odds of having an HSIL increased approximately six times for the p16/Ki-67 positive cases. In HIV-infected individuals, all the biomarkers showed a significant association with HSIL, except for hrHPV DNA, with the strongest association observed for p16/Ki-67. The odds of HSIL increased almost 21 times in those positive for this biomarker. Our results encourage further investigation on the use of p16/Ki-67 dual staining in anal cancer screening for HIV-uninfected and HIV-infected MSM.
RESUMO
Mucosal Human Papillomaviruses (HPVs) play a role in the development of a subset of head and neck cancers. Cutaneous HPVs are abundantly present in the oral cavity. The determinants of these infections have not been extensively investigated. We assessed the correlates of oral infection by alpha and beta and/or gamma HPVs in HIV-infected and uninfected men who have sex with men (MSM). Oral rinse-and-gargles were collected with a mouthwash. Alpha and beta/gamma HPVs were detected using the Linear Array HPV genotyping test and a multiplex PCR combined with Luminex technology, respectively. Multiple logistic regression was performed to identify independent predictors of oral HPV infection. Overall, 193 HIV-uninfected and 117 HIV-infected MSM were enrolled. Among HIV-infected MSM, the only determinant of alpha HPV infection was the number of lifetime oral sex partners (AOR: 8.26, 95% CI: 2.26-30.16). The strongest determinant of beta/gamma HPV infection was represented by practicing condomless receptive oral sex (AOR: 10.76, 95% CI: 1.56-74.17). Age was independently associated with alpha HPV infection in HIV-uninfected MSM. Beta/gamma HPV infection was not associated with sexual behavior in these subjects. In conclusion, predictors of oral infection differ between HIV-infected and uninfected MSM, as well as between alpha and beta/gamma HPVs.
RESUMO
BACKGROUND: The study presents cross-sectional accuracy of E6 and E7 (E6/E7) mRNA detection and p16/ki67 dual staining, alone or in combination with cytology and human papillomavirus (HPV)16/18 genotyping, as a triage test in HPV DNA-positive women and their impact on cervical intraepithelial neoplasia (CIN2+) overdiagnosis. METHODS: Women aged 25-64 years were recruited. HPV DNA-positive women were triaged with cytology and tested for E6/E7 mRNA and p16/ki67. Cytology positive women were referred to colposcopy, and negatives were randomly assigned to immediate colposcopy or to 1-year HPV retesting. Lesions found within 24 months since recruitment were included. All P values were 2-sided. RESULTS: 40 509 women were recruited, and 3147 (7.8%) tested HPV DNA positive; 174 CIN2+ were found: sensitivity was 61.0% (95% confidence interval [CI] = 53.6 to 68.0), 94.4% (95% CI = 89.1 to 97.3), and 75.2% (95% CI = 68.1 to 81.6) for cytology, E6/E7 mRNA, and p16/ki67, respectively. Immediate referral was 25.6%, 66.8%, and 28.3%, respectively. Overall referral was 65.3%, 78.3%, and 63.3%, respectively. Cytology or p16/ki67, when combined with HPV16/18 typing, reached higher sensitivity with a small impact on referral. Among the 2306 HPV DNA-positive and cytology-negative women, relative CIN2+ detection in those randomly assigned at 1-year retesting vs immediate colposcopy suggests a -28% CIN2+ regression (95% CI = -57% to +20%); regression was higher in E6/E7 mRNA-negatives (Pinteraction = .29). HPV clearance at 1 year in E6/E7 mRNA and in p16/ki67 negative women was about 2 times higher than in positive women (Pinteraction < .001 for both). CONCLUSIONS: p16/ki67 showed good performance as a triage test. E6/E7 mRNA showed the highest sensitivity, at the price of too high a positivity rate to be efficient for triage. However, when negative, it showed a good prognostic value for clearance and CIN2+ regression.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Antígeno Ki-67/genética , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/diagnóstico , RNA Mensageiro/análise , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Biomarcadores/análise , Estudos Transversais , DNA Viral/análise , DNA Viral/genética , Proteínas de Ligação a DNA/genética , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prognóstico , RNA Mensageiro/genética , Proteínas Repressoras/genética , Triagem , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND: The objective of this study was to describe the determinants of adequacy and positivity of the p16/Ki-67 assay in a human papillomavirus (HPV)-positive screening population enrolled within the New Technologies for Cervical Cancer 2 (NTCC2) study. METHODS: ThinPrep slides were immunostained for p16/Ki-67; each slide had 3 reports from different laboratories. The authors included population-related, sampling-related/staining-related, and interpretation-related variables in the analyses. Adequacy and positivity proportions were stratified by variables of interest. Univariate and multivariate logistic models were used to identify determinants of adequacy and positivity. RESULTS: In total, 3100 consecutive HPV-positive cases were analyzed. Because every slide was interpreted by 3 centers, 9300 reports were obtained, including 905 (9.7%) that were inadequate and 2632 (28.3%) that were positive. The percentage of cases in which all 3 reports were inadequate increased with increasing age of the women and with inadequate cytology. The highest percentage of adequacy in all 3 reports and of cases with all 3 reports positive was observed in specimens from women who had grade ≥2 cervical intraepithelial neoplasia (CIN2+), atypical squamous cells of undetermined significance or more severe (ASC-US+) cytology, or mRNA positivity. The number of inadequate reports was significantly associated with increasing age, inadequate cytology, mRNA negativity, and scant cellularity. A positive p16/Ki-67 report was associated with an ASC-US+ result and with a positive mRNA result in cases both with and without CIN2+ but was associated with an HPV type 16 and/or 18 infection only in CIN2+ cases. The presence of CIN2+ was strongly associated with dual staining positivity. CONCLUSIONS: The interpretation of p16/Ki-67 results may be influenced by several different variables, all of which are part of the steps in the procedure, and by the characteristics of the screened population.