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1.
Br J Radiol ; 93(1111): 20190464, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32391712

RESUMO

OBJECTIVES: To analyze survival outcomes in patients with oropharygeal cancer treated with primary intensity modulated radiotherapy (IMRT) using decision tree algorithms. METHODS: A total of 273 patients with newly diagnosed oropharyngeal cancer were identified between March 2010 and December 2016. The data set contained nine predictor variables and a dependent variable (overall survival (OS) status). The open-source R software was used. Survival outcomes were estimated by Kaplan-Meier method. Important explanatory variables were selected using the random forest approach. A classification tree that optimally partitioned patients with different OS rates was then built. RESULTS: The 5 year OS for the entire population was 78.1%. The top three important variables identified were HPV status, N stage and early complete response to treatment. Patients were partitioned in five groups on the basis of these explanatory variables. CONCLUSION: The proposed classification tree could help to guide future research in oropharyngeal cancer field. ADVANCES IN KNOWLEDGE: Decision tree method seems to be an appropriate tool to partition oropharyngeal cancer patients.


Assuntos
Neoplasias Orofaríngeas/mortalidade , Radioterapia de Intensidade Modulada/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Árvores de Decisões , Feminino , Fluordesoxiglucose F18 , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/radioterapia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/mortalidade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Resultado do Tratamento
2.
Otolaryngol Head Neck Surg ; 162(5): 693-701, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32151208

RESUMO

OBJECTIVE: Extranodal extension (ENE) is known to be associated with poor outcomes in head and neck squamous cell carcinoma. The objective of this study is to examine the impact of extent of ENE on survival in oropharyngeal carcinoma in the human papillomavirus (HPV) era. STUDY DESIGN: Retrospective database review. SETTING: Review of the National Cancer Database. SUBJECTS AND METHODS: The National Cancer Database was used to examine surgically treated head and neck squamous cell carcinoma of the tonsil and base of tongue from 2010 to 2015. Nodes available for pathologic examination were classified as ENE negative (-), ENE clinically (+), or ENE (+) on pathology only. The primary outcome was overall survival. Cox regression modeling was used to examine the effect of ENE on survival while controlling for patient demographics, HPV status, stage, adjuvant radiation, and chemotherapy. RESULTS: Of the 66,106 patients identified, 16,845 were treated with surgery ± adjuvant therapy, 8780 of whom were known HPV+. Overall 5-year survival for this group was 86%. Documented ENE was associated with over a 60% decrease in survival for clinical (hazard ratio [HR], 1.63) and pathologic (HR, 1.62) ENE compared to negative ENE, after adjustment for stage, adjuvant radiation ± chemotherapy, HPV, and other variables. No significant differences were found between clinical and pathologic ENE (HR, 1.001). CONCLUSION: While both surgically resected clinical and pathologic ENE are associated with decreased survival, no significant differences are observed between the two. The impact of these observations on potential de-escalation therapeutic strategies requires further study.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Extensão Extranodal , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/cirurgia , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos
3.
Int J Cancer ; 146(8): 2166-2174, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31269236

RESUMO

In cancer epidemiological studies, determination of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) typically depends on the availability of tumor tissue testing, and/or tumor tissue access. Identifying alternative methods for estimating HPV status can improve the quality of such studies when tissue is unavailable. We developed multiple predictive models for tumor HPV status and prognosis by combining both clinico-epidemiological variables and either serological multiplex assays of HPV or multiple imputation of HPV status (HPVmi ). Sensitivity, specificity and accuracy of these methods compared to either p16 immunostaining (p16 IHC) or survival were assessed. When compared to a reference of tumor tissue p16 IHC in 783 OPSCC patients, the clinic-HPVsero model incorporating a composite of 20 HPV serological antibodies (HPVsero ) and 4 clinical factors (c-index: 0.96) performed better than using HPVsero (c-index: 0.92) or HPVmi (c-index: 0.76) alone. However, the model that contained a single HPV16 E6 antibody combined with four clinical variables, performed extremely well (clinic-s1-16E6; c-index: 0.95). When defining HPV status by HPVsero , s1-16E6, HPVmi or through p16 IHC, each of these definitions demonstrated improved overall and disease-free survival in HPV-positive OPSCC patients, when compared to HPV-negative patients (adjusted hazard ratios between 0.25 and 0.63). Our study demonstrates that when blood samples are available, a model that utilizes a single s1-16E6 antibody combined with several clinical features has excellent test performance characteristics to estimate HPV status and prognosis. When neither blood nor tumor tissue is available, multiple imputation, calibrated on local population characteristics, remains a viable, but suboptimal option.


Assuntos
Neoplasias Orofaríngeas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/imunologia , Neoplasias Orofaríngeas/sangue , Neoplasias Orofaríngeas/mortalidade , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/virologia , Proteínas Repressoras/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Taxa de Sobrevida
4.
Acta Otolaryngol ; 139(10): 913-917, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31430224

RESUMO

Background: Expression of the epidermal growth factor receptor (EGFR) and human papillomavirus (HPV) DNA can serve as independent prognostic factors in squamous cell carcinoma (SCC) of the larynx. EGFR correlation with the course of disease and its effect on survival makes EGFR expression a negative prognostic factor, whereas HPV DNA is a positive prognostic factor. Aim: To assess the association of EGFR expression with clinical outcome of laryngeal HPV SCC. Materials and methods: This retrospective study included 196 SCC patients operated on at the Department of ENT, Head and Neck Surgery, Split University Hospital Center in Split, Croatia, between 1 January 2000 and 31 December 2009. Results: The association of HPV infection and EGFR expression was found to be statistically significant, and so was the difference in survival between patient groups with different HPV to EGFR expression ratio. Conclusions: The group of laryngeal HPV SCC patients with increased EGFR expression had shorter survival, confirming EGFR as a major component in predicting patient prognosis and survival. Significance: This article confirms the importance of EGFR expression as a biomarker in laryngeal SCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Receptores ErbB/metabolismo , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/virologia , Infecções por Papillomavirus/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Neoplasias Laríngeas/mortalidade , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
5.
Acta Oncol ; 58(12): 1745-1751, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31282249

RESUMO

Purpose: To determine if anal cancer patients with HPV positive disease have different overall survival (OS) compared to those with HPV negative disease, and to elucidate differences in the association between radiation dose and OS.Patients and methods: We utilized the National Cancer Database (NCDB) registry to identify a cohort of non-metastatic anal cancer patients treated with curative intent between 2008 and 2014. Propensity score matching was used to account for potential selection bias between patients with HPV positive and negative disease. Multivariable Cox regression was used to determine the association between HPV status and OS. Kaplan-Meier methods were used to compare actuarial survival estimates.Results: We identified 5927 patients with tumor HPV status for this analysis, 3523 (59.4%) had HPV positive disease and 2404 (40.6%) had HPV negative disease. Propensity-matched analysis demonstrated that patients with HPV positive locally advanced (T3-4 or node positive) anal cancer had better OS (HR = 0.81 (95%CI: 0.68-0.96), p=.018). For patients with early stage disease (T1-2 and node negative) there was no difference in OS (HR = 1.11 (95%CI: 0.86-1.43), p=.43). In the unmatched cohort, we found a significant improvement in OS with increasing radiation dose only for patients with locally advanced, HPV negative disease (p<.001). In those patients, significant improvement in OS compared to the group receiving 30-45 Gy was seen for increasing doses up to 55-60 Gy, but not beyond 60 Gy.Conclusion: We found HPV to be a significant prognostic marker in anal tumors, especially for locally advanced disease. We further found that higher radiation dose up to 55-60 Gy was associated with better OS, but only for patients with locally advanced, HPV negative disease.


Assuntos
Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/radioterapia , Papillomaviridae , Infecções por Papillomavirus/mortalidade , Fatores Etários , Neoplasias do Ânus/patologia , Neoplasias do Ânus/virologia , Bases de Dados Factuais , Feminino , Papillomavirus Humano 16 , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Dosagem Radioterapêutica , Análise de Regressão , Viés de Seleção , Sensibilidade e Especificidade , Fatores Sexuais
6.
Cancer Immunol Immunother ; 68(8): 1263-1272, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31240326

RESUMO

BACKGROUND: An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC. MATERIALS AND METHODS: A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels. CONCLUSION: Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Orofaríngeas/diagnóstico , Papillomaviridae/fisiologia , Infecções por Papillomavirus/diagnóstico , Inibidor Tecidual de Metaloproteinase-1/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/mortalidade , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Metaloproteinase 8 da Matriz/sangue , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/mortalidade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/mortalidade , Prognóstico , Análise de Sobrevida
7.
BMC Cancer ; 19(1): 419, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060525

RESUMO

BACKGROUND: One-third of cervical cancer patients are still diagnosed at advanced stages. The five-year survival rate is decreased in about 50% of advanced stage cervical cancer patients worldwide, and the clinical outcomes are remarkably varied and difficult to predict. One of the miRNAs known to be associated with cancer tumorigenesis is miR-944. However, the prognostic value of miR-944 in cervical cancer has not been fully investigated. The aim of this study was to analyze clinical significance and prognostic value of miR-944 in cervical cancer. METHODS: The expression levels of miR-944 were detected using quantitative reverse transcription polymerase chain reaction in five types of cervical cancer cell lines and 116 formalin-fixed paraffin-embedded (FFPE) cervical tissues. The association between the expression levels of miR-944 and prognostic value was analyzed using the Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: The expression levels of miR-944 in cervical cancer tissues were significantly higher compared with those in normal tissues (P < 0.0001). Moreover, the expression levels of miR-944 in cervical cancer cell lines and FFPE tissues with human papillomavirus (HPV) infection were significantly higher compared to those without HPV infection (P < 0.01 and P = 0.02). High miR-944 expression was also markedly associated with bulky tumor size (P = 0.026), advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.042), and lymph node metastasis (P = 0.030). In particular, high miR-944 expression group showed shorter overall survival than the low miR-944 expression group in the advanced FIGO stage (84.4% vs. 44.4%, HR = 4.0, and P = 0.01). CONCLUSIONS: These results suggest that miR-944 may be used as a novel biomarker for improving prognosis and as a potential therapeutic target.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/genética , Adulto , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Colo do Útero/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prognóstico , Estudos Retrospectivos , Regulação para Cima , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
8.
Gynecol Oncol ; 154(1): 118-123, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31088688

RESUMO

AIM: In countries like Denmark, cervical cancer incidence is at present relatively high in elderly women, while routine screening stops at age 65 years. On this background, all women aged 69 and above were invited to human papillomavirus (HPV)-screening in Denmark in 2017. METHODS: Women were identified from the Central Population Register and personally invited by digital or ordinary mail to have a screening sample taken by their general practitioner. In four regions, samples were tested for high risk (HPV) with the cobas 4800® HPV-assay, and in the last region with the BD Onclarity® HPV-assay. Participation rate, prevalence of high risk HPV, and proportion of positive samples with HPV16, HPV18, and other high risk HPV-types were tabulated by 5-year age-groups. RESULTS: 455,612 women were invited, and 30.2% (95 confidence interval (CI) 30.0-30.3) participated. Average age of participants was 74.6 years. Overall, 4.3% (95% CI 4.1-4.4) of participants were HPV-positive, of whom 24% had HPV 16/18. HPV-prevalence decreased slightly from 4.5% in women aged 69-73 years to 3.1% in women aged 84-88 years, but was 5.2% in the very small group of participants aged 89+ years. CONCLUSION: Invitation to HPV-screening was well received by elderly women. The HPV-prevalence decreased slightly with increasing age. No rebound of HPV-prevalence after menopause was found when our data were combined with previously published Danish data from younger women. The presently relatively high cervical cancer incidence in elderly women was not reflected in the HPV-prevalence.


Assuntos
Infecções por Papillomavirus/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Emigração e Imigração/estatística & dados numéricos , Feminino , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Infecções por Papillomavirus/mortalidade , Pós-Menopausa , Prevalência , Sistema de Registros , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
9.
Anticancer Res ; 39(4): 1907-1914, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952732

RESUMO

BACKGROUND/AIM: HPV-mediated oropharyngeal squamous cell carcinoma is associated with an increased survival. The prognostic value of HPV status for other primary sites is unclear. We aimed to assess the effect of HPV status on overall survival in patients with non-oropharyngeal head and neck squamous cell carcinoma (non-OPSCC) using the National Cancer Database (NCDB). PATIENTS AND METHODS: Adults with non-OPSCC [gum, lip, floor of mouth, tongue (excluding base), hypopharynx, nasopharynx, other pharynx] and known HPV status were included in our study. Associations between HPV status, primary site, patient characteristics and overall survival (OS) were assessed. RESULTS: HPV positivity was associated with a better OS compared to HPV-negative patients (HR=0.83, 95%CI=0.74-0.93, p<0.001). Female gender, gum, lip, nasopharynx primaries, and private insurance predicted for improved OS. CONCLUSION: HPV positivity and female gender are good prognostic factors in non-OPSCC. Routine HPV testing should be considered for HPV positive non-OPSCC, as well as studies evaluating de-escalation of treatment if this association is confirmed.


Assuntos
Neoplasias Orofaríngeas/epidemiologia , Infecções por Papillomavirus/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Fatores de Tempo , Estados Unidos/epidemiologia
10.
Mod Pathol ; 32(8): 1189-1196, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30911077

RESUMO

Human papillomaviruses (HPV) are the causative agents of virtually all cervical carcinomas. Nevertheless, a small proportion of cervical cancer are negative for HPV, although the significance of this finding remains unclear. We aimed to provide insight into the differential clinico-pathological characteristics of this unusual subset of HPV-negative cervical cancer. We performed HPV-DNA detection using a highly sensitive PCR test (SPF10) and p16 immunostaining in 214 cervical carcinomas specimens from women treated at the Gynecological Oncology Unit of the Hospital Clinic (Barcelona, Spain) from 2012 to 2015. The clinical and pathological characteristics, including disease-free survival and overall survival, of HPV-negative and -positive cervical carcinomas were compared. Twenty-one out of 214 tumors (10%) were negative for HPV DNA. HPV-negative tumors were more frequently of the non-squamous type (9/21, 43% vs. 37/193, 19%; p < 0.01) and showed negative p16 staining (9/21; 43% vs. 7/193; 4%; p < 0.01). HPV-negative tumors were more frequently diagnosed at advanced FIGO stage (19/21, 91% vs. 110/193, 57%; p < 0.01) and more frequently had lymph node metastases (14/21, 67% vs. 69/193, 36%; p < 0.01). Patients with HPV-negative cervical cancer had a significantly worse disease-free survival (59.8 months, 95% confidence interval 32.0-87.6 vs. 132.2 months, 95% confidence interval 118.6-145.8; p < 0.01) and overall survival (77.0 months, 95% confidence interval 47.2-106.8 vs. 153.8 months, 95% confidence interval 142.0-165.6; p = 0.01) than women with HPV-positive tumors. However, only advanced FIGO stage and lymph node metastases remained associated with a poor disease-free survival and overall survival on multivariate analysis. In conclusion, our results suggest that a low percentage of cervical cancer arise via an HPV-independent pathway. These HPV-negative tumors are diagnosed at advanced stages, show higher prevalence of lymph nodes metastases and have an impaired prognosis.


Assuntos
DNA Viral/genética , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Inibidor p16 de Quinase Dependente de Ciclina/análise , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Papillomaviridae/química , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/terapia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Neoplasias do Colo do Útero/química , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/terapia , Adulto Jovem
11.
Curr Opin Oncol ; 31(3): 160-168, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30844888

RESUMO

PURPOSE OF REVIEW: The systemic therapies available in recurrent and metastatic head and neck squamous cell carcinoma to date are palliative-intent treatments in most cases. However, a small subgroup of patients derives unconventional benefit and become long-term survivors, achieving cure in some cases. This review focusses on this group of patients, discusses recent literature and suggests plausible molecular hypothesis. RECENT FINDINGS: Human papillomavirus-related disease is known to confer a better prognosis in metastatic patients, probably because of its greater sensitivity to systemic therapies. This group of patients seems to have a greater immune activation, which could partly explain this fact. Moreover, the use of antiepidermal growth factor receptor therapies in the metastatic setting has doubled the prevalence of long-term survivors. One of the most plausible explanations is the immune-modulatory effect of cetuximab mediated by antibody-dependent cell-mediated cytotoxicity.These facts, along with the recent encouraging results of checkpoint inhibitors in this disease, give hope that these therapies will not only improve survival but also increase the prevalence of long-term survivors. SUMMARY: Long-term survivors merit our utmost attention as an in-depth study of these patients could help us to better understand the tumour biology and allow us to develop robust biomarkers and effective targeted therapies, which could in turn lead to a true paradigm shift.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias de Cabeça e Pescoço/mortalidade , Recidiva Local de Neoplasia/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/virologia , Infecções por Papillomavirus/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
12.
Am J Surg Pathol ; 43(4): 466-474, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30720532

RESUMO

The International Endocervical Adenocarcinoma Criteria and Classification (IECC) categorizes endocervical adenocarcinomas (ECAs) on the basis of morphologic features linked to etiology (ie, human papilloma virus [HPV] infection), resulting in separation of ECAs into HPV-associated (HPVA) and unassociated or non-HPVA (NHPVA) types. NHPVAs are reported to be large and present at high stage in older individuals. Our aim was to examine the clinical outcomes in these tumor types. Full slide sets of 205 ECAs were collected from 7 institutions worldwide and classified on the basis of IECC criteria and the presence or absence of HPV. Clinical and morphologic parameters were correlated with follow-up data. Statistical analysis of overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were conducted using the Kaplan-Meier survival analysis and compared using the log-rank test for univariate analysis. Multivariate survival analysis was conducted, and the survival endpoints considered were OS, DFS, and PFS. Statistically significant survival differences (OS, DFS, and PFS) were found when comparing the following categories: HPVA>NHPVA (ie, survival was superior in the setting of HPVAs), including patients treated with surgery followed by adjuvant therapy; usual-type HPVA>mucinous HPVA; FIGO grade 3 HPVA>NHPVA; HPVA>NHPVA, both with lymphovascular invasion; and HPVA>NHPVA in patients with pelvic recurrences. Although there were trends favoring HPVA outcomes over those of NHPVA, these differences were not statistically significant in the following categories: mucinous HPVA versus NHPVA; HPVA versus NHPVA, both with lymph node metastases at presentation; and HPVA versus NHPVA in patients with distant metastasis. Survival for both HPVA and NHPVA was similar when surgery without adjuvant therapy was used. FIGO grading did not have prognostic significance in HPVAs. Multivariable analysis of HPVAs indicated nearly significant statistical associations between stage and both OS and DFS (P=0.07 and 0.06, respectively), and between Silva invasion pattern and OS (P=0.09). Multivariate analysis of NHPVAs indicated a statistically significant association between OS and age (P=0.03), stage (P=0.02) and tumor size (P=0.002), and between DFS and stage (P=0.004) and tumor size (P=0.004). Multivariate analysis of HPVAs and NHPVAs together revealed nearly significant associations between OS and HPV status and stage (both [P=0.06]). For DFS, stage was a significant variable (P=0.04), whereas HPV status and tumor size were nearly significant (P=0.06 and 0.07, respectively). Clinical outcome studies support the idea that the IECC classification not only separates ECAs on the basis of HPV status (usually assessed on H&E slides), but also has important clinical relevance.


Assuntos
Adenocarcinoma/classificação , Adenocarcinoma/virologia , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/virologia , Adenocarcinoma/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/mortalidade , Neoplasias do Colo do Útero/mortalidade , Adulto Jovem
13.
Acta Otolaryngol ; 139(2): 206-210, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30794027

RESUMO

BACKGROUND: Human papillomavirus-positive (HPV+) base of tongue squamous cell carcinoma (BOTSCC) has a better outcome than corresponding HPV- cancer. TLR5 and TLR7 expression was previously shown to differ depending on HPV - status and correlate with outcome in oropharyngeal squamous cell carcinoma. AIMS/OBJECTIVES: For validation, TLR5 and TLR7 were analyzed in a BOTSCC-cohort for correlation with HPV, survival, CD4+ and CD8+ tumor-infiltrating lymphocyte (TIL) counts, the latter being a well-documented prognostic marker. MATERIALS AND METHODS: BOTSCC biopsies, (49HPV+/28HPV-) were analyzed by immunohistochemistry for TLR5 and TLR7, and correlated with the above parameters. RESULTS: TLR5 expression was more frequently absent/weak than medium/strong in HPV+ compared to HPV- BOTSCC (p < .001). The opposite was observed for TLR7 (p < .007). TLR5 and TLR7 expression did not correlate to survival in either the HPV- or HPV+ cases, or to CD4+ TILs. TLR5, (but not TLR7) expression was correlated to CD8+ TIL counts (p = .023). CONCLUSION AND SIGNIFICANCE: Absent/weak TLR5 and medium/strong TLR7 expression was validated as more frequent in HPV+ compared with HPV- BOTSCC. A correlation between CD8+ TIL counts, and TLR5 expression was disclosed, but not with TLR7. Therefore, it could be useful to investigate TLR7 further as a potential independent prognostic marker.


Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Receptor 4 Toll-Like/genética , Receptor 5 Toll-Like/genética , Neoplasias da Língua/virologia , Idoso , Biópsia por Agulha , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/patologia , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Taxa de Sobrevida , Suécia , Neoplasias da Língua/genética , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia
14.
Int J Gynecol Cancer ; 29(3): 459-465, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30733276

RESUMO

OBJECTIVE: To assess the prognostic value of human papillomavirus (HPV) viral load in locally advanced cervical carcinoma treated with radical concurrent chemoradiotherapy. METHODS: From January 2012 to October 2013, a total of 246 locally advanced cervical carcinoma patients were included in this retrospective study. HPV DNA status was tested by Hybrid Capture 2 assay. Tumor size was measured on T2WI. All the patients in the study received concurrent cisplatin-based chemoradiotherapy with intensity-modulated radiotherapy and three-dimensional brachytherapy. Survival rate was calculated by the Kaplan-Meier method, and a log-rank test was used to compare the survival. Multivariate analysis employed the Cox regression model. RESULTS: The median follow-up time was 52 months. The median value of HPV DNA was 163.13 relative light unit/cut-off (RLU/CO) (range 1.65-2162.62 RLU/CO). The 5-year overall survival, distant metastasis-free survival of patients in the low HPV DNA group (HPV DNA ≤ 163.13 RLU/CO) and the high HPV DNA group (HPV DNA > 163.13 RLU/CO) were 46.3 % vs 58.5 % (p = 0.009) and 65.9 % vs 75.6% (p = 0.003), respectively. Multivariate analysis showed that the HPV DNA, tumor size, and International Federation of Gynecology and Obstetrics (FIGO) stage were independent prognostic factors for overall survival and distant metastasis-free survival. We choose the tumor size and HPV DNA as the risk stratification factors to build a new prediction marker which can better predict overall survival for locally advanced cervical cancer than can the FIGO stage. CONCLUSIONS: HPV DNA may be a useful biomarker for locally advanced cervical cancer. Low HPV load predicts a worse survival. The new marker based on risk stratification by combining HPV DNA and tumor size is better associated with overall survival of locally advanced cervical cancer treated with concurrent chemoradiotherapy.


Assuntos
DNA Viral/análise , Papillomaviridae/genética , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virologia , Quimiorradioterapia , Cisplatino/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Risco , Análise de Sobrevida , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Carga Viral
15.
Ann Oncol ; 30(4): 629-636, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30657857

RESUMO

BACKGROUND: In the era of precision medicine and HPV-related oropharyngeal squamous cell carcinoma (OPSCC), it is relevant to assess the risk of not only survival, but also the risk of local, regional, or distant treatment failure. The UICC 8th edition uses the surrogate marker p16 to stratify for HPV association but discordance between p16 status and HPV association has been shown. The purpose of this study was to develop a prognostic model to predict the risk of local, regional, and distant metastases and non-cancer-related death for patients with OPSCC, test the prognostic relevance of adding HPV DNA and p16 status, and validate the findings in an independent external dataset. PATIENTS AND METHODS: Consecutive patients diagnosed with OPSCC and treated with curative radiotherapy with or without cisplatin in eastern Denmark from 2000 to 2014 were included. Characteristics included age, gender, TNM stage, smoking habits, performance status, and HPV status assessed with p16 and HPV DNA. The information was used to develop a prognostic model for first site of failure with four competing events: recurrence in T-, N-, and M-site, and death with no evidence of disease. RESULTS: Overall 1243 patients were eligible for the analysis. A prognostic model with the four events was developed and externally validated in an independent dataset with a heterogeneously treated patient population from another institution. The individual prognostication from the competing risk analysis is displayed in a user friendly online tool (https://rasmussen.shinyapps.io/OPSCCmodelHPV_p16/). Replacing p16 status with the combined variable HPV/p16 status influenced the HR and patients with HPV-/p16+ had significantly higher HR of M-site recurrence than HPV+/p16+ with a HR = 2.56; CI [1.30; 5.02]; P = 0.006 (P = 0.013 in the validation cohort). CONCLUSION: Patients with HPV-/p16+ have significantly higher risk of M-site recurrence and could potentially be relevant candidates for clinical trials testing systemic treatments in combination with conventional treatments.


Assuntos
Biomarcadores Tumorais/análise , Modelos Biológicos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Orofaríngeas/terapia , Infecções por Papillomavirus/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Biomarcadores Tumorais/genética , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Tomada de Decisão Clínica , Inibidor p16 de Quinase Dependente de Ciclina/análise , DNA Viral/isolamento & purificação , Conjuntos de Dados como Assunto , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/patologia , Valor Preditivo dos Testes , Prognóstico , Medição de Risco/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
16.
Otolaryngol Head Neck Surg ; 160(6): 1042-1047, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30642220

RESUMO

OBJECTIVE: (1) To identify p16 protein in laryngeal squamous cell carcinoma (LSCC) specimens and to correlate it with the presence of human papillomavirus (HPV) found in these specimens from a previous study. (2) To analyze p16 impact on 10-year overall and disease-free survival. STUDY DESIGN: Retrospective case series with oncologic database chart review. SETTING: Academic tertiary care hospital. SUBJECTS: A total of 123 samples of LSCC (taken from the glottis only) from patients treated with primary surgical resection between 1977 and 2005. METHODS: p16 protein expression was analyzed through immunohistochemistry and compared with the presence of HPV established in our previous studies. Results were compared with histologic, clinicopathologic, and survival parameters, with a 10-year follow-up. RESULTS: Of the samples, 39.02% were positive for p16, but only 11.38% were positive for both p16 and HPV. The p16+ cohort showed a significant improvement in disease-free survival ( P = .0022); statistical significance was not achieved for overall survival. p16+ cases had fewer relapses over time, with no relapses after a 2-year follow-up. Age at the time of diagnosis and tobacco consumption were the only epidemiologic factors that influenced overall survival. CONCLUSION: The expression of p16 protein was a beneficial prognostic factor for disease-free survival among patients with LSCC of the glottis, with no relapses after a 2-year follow-up.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Inibidor p16 de Quinase Dependente de Ciclina/sangue , Glote , Neoplasias Laríngeas/mortalidade , Papillomaviridae , Infecções por Papillomavirus/mortalidade , Idoso , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/virologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/complicações , Estudos Retrospectivos , Taxa de Sobrevida
17.
Aktuelle Urol ; 50(5): 491-501, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-30227445

RESUMO

BACKGROUND: Human papillomavirus (HPV) infection plays an important role in the pathogenesis of penile squamous cell carcinoma (PSCC) in about one third of the affected patients. Initial data indicate that HPV status could facilitate optimised risk stratification and individualised targeted therapy. The polymerase chain reaction (PCR) assay is the reference method for detection of HPV DNA. It is unclear if alternatives such as in situ hybridisation (ISH) or various surrogate markers (defined as immunohistochemical detection of p16INK4a, histological subtype, tumour invasion front, koilocytosis) are sufficient to determine HPV status METHODS: In this single centre study on 34 patients with PSCC, multiplex nested PCR and ISH were conducted for HPV detection and identification of HPV DNA genotypes. Various histological criteria and p16INK4a were determined by central review. The influence of different criteria on cancer-specific mortality (CSM) was investigated with the Cox proportional hazards models (FU: 92 mo.). Furthermore, the discriminative qualities of various tumour invasion patterns (i. e., pT-classification 7th vs. 8th ed.) for CSM prediction were compared. RESULTS: Pursuant to PCR assay, HPV DNA was detected in 26 % of patients (n = 9). ISH and the examined histological criteria were of inadequate quality in the prediction of HPV status (p > ;0.3). Test parameters of p16INK4a were calculated as follows: sensitivity 66.7 %, specificity 84 %, positive predictive value 60 %, negative predictive value 87.5 %, overall agreement 79.4 % (Area-Under-Curve: 0.753, p = 0.026). None of the examined HPV criteria significantly influenced CSM. In comparison to the 7th pT-edition, the 8th version was superior in CSM prediction (c-indices 70.2 % vs. 72.9 %). In addition to penile corpora invasion, infiltration of the urethra had no independent predictive value. Regrouping of the corpora invasion patterns, as proposed by us, resulted in an increase in discriminative quality (c-index 77.9 %). CONCLUSIONS: In contrast to ISH and the examined histological criteria, p16INK4a allows a reasonable prediction of HPV status. Neither HPV DNA nor its surrogate markers independently impacted CSM. As urethral tumour invasion does not independently influence CSM, the recent pT classification can be considered useful for prognosis.


Assuntos
Carcinoma de Células Escamosas/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA Viral/genética , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Neoplasias Penianas/diagnóstico , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Testes de DNA para Papilomavírus Humano , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/patologia , Neoplasias Penianas/mortalidade , Neoplasias Penianas/patologia , Pênis/patologia , Pênis/virologia , Prognóstico
18.
JAMA Oncol ; 5(1): 67-73, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30267032

RESUMO

Importance: In recurrent human papilloma virus (HPV)-driven cancer, immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies produces tumor regression in only a minority of patients. Therapeutic HPV vaccines have produced strong immune responses to HPV-16, but vaccination alone has been ineffective for invasive cancer. Objective: To determine whether the efficacy of nivolumab, an anti-PD-1 immune checkpoint antibody, is amplified through treatment with ISA 101, a synthetic long-peptide HPV-16 vaccine inducing HPV-specific T cells, in patients with incurable HPV-16-positive cancer. Design, Setting, and Participants: In this single-arm, single-center phase 2 clinical trial, 24 patients with incurable HPV-16-positive cancer were enrolled from December 23, 2015, to December 12, 2016. Duration of follow-up for censored patients was 12.2 months through August 31, 2017. Interventions: The vaccine ISA101, 100 µg/peptide, was given subcutaneously on days 1, 22, and 50. Nivolumab, 3 mg/kg, was given intravenously every 2 weeks beginning day 8 for up to 1 year. Main Outcomes and Measures: Assessment of efficacy reflected in the overall response rate (per Response Evaluation Criteria in Solid Tumors, version 1.1). Results: Of the 24 patients (4 women and 20 men; 22 with oropharyngeal cancer; median age, 60 years [range, 36-73 years]), the overall response rate was 33% (8 patients; 90% CI, 19%-50%). Median duration of response was 10.3 months (95% CI, 10.3 months to inestimable). Five of 8 patients remain in response. Median progression-free survival was 2.7 months (95% CI, 2.5-9.4 months). Median overall survival was 17.5 months (95% CI, 17.5 months to inestimable). Grades 3 to 4 toxicity occurred in 2 patients (asymptomatic grade 3 transaminase level elevation in 1 patient and grade 4 lipase elevation in 1 patient), requiring discontinuation of nivolumab therapy. Conclusions and Relevance: The overall response rate of 33% and median overall survival of 17.5 months is promising compared with PD-1 inhibition alone in similar patients. A randomized clinical trial to confirm the contribution of HPV-16 vaccination to tumoricidal effects of PD-1 inhibition is warranted for further study. Trial Registration: ClinicalTrials.gov identifier: NCT02426892.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Papillomavirus Humano 16/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Nivolumabe/uso terapêutico , Infecções por Papillomavirus/tratamento farmacológico , Vacinas contra Papillomavirus/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Progressão da Doença , Feminino , Papillomavirus Humano 16/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/mortalidade , Neoplasias/virologia , Nivolumabe/efeitos adversos , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/efeitos adversos , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Fatores de Tempo
19.
Otolaryngol Head Neck Surg ; 160(3): 494-501, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30226795

RESUMO

OBJECTIVE: Evaluate serum C-reactive protein (CRP) in human papillomavirus (HPV)-positive oropharynx cancer as compared with HPV-negative oropharynx cancer and determine if CRP levels were associated with overall survival and/or recurrence-free survival. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary care academic cancer center between 2007 and 2010. SUBJECTS AND METHODS: Among patients with oropharynx cancer and confirmed HPV status, plasma CRP levels were measured with a high-sensitivity ELISA kit. Multivariable logistic regression analysis compared 4 categories of CRP (low, moderate, high, very high) between the HPV-positive and HPV-negative groups. Kaplan-Meier methods and Cox regression models were used to determine overall survival and recurrence-free survival by CRP level in both populations. RESULTS: Between 113 HPV-positive and 110 HPV-negative patients, CRP levels were significantly higher in the HPV-positive group, but these levels did not demonstrate a statistically significant dose-response trend. Higher CRP levels were also associated with reduced overall survival ( P = .016) and recurrence-free survival ( P < .001) within the HPV-negative group in univariable analysis; in multivariate analysis, the comparisons were not significantly different. Within HPV-positive oropharynx cancer, CRP levels were not significantly associated with overall survival or recurrence-free survival in univariable or multivariable analyses. CONCLUSION: Circulating CRP was higher in HPV-positive versus HPV-negative oropharynx cancer. Among HPV-negative patients, higher CRP levels were associated with reduced survival.


Assuntos
Proteína C-Reativa/metabolismo , Neoplasias Orofaríngeas/sangue , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/sangue , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Modelos de Riscos Proporcionais , Taxa de Sobrevida
20.
Cancer Cytopathol ; 127(1): 35-43, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30468701

RESUMO

BACKGROUND: Human papillomavirus (HPV)-related squamous cell carcinoma (SqCC) of the oropharynx is an epidemiologically and clinically distinct form of SqCC that is associated with an improved prognosis. However, HPV-related small cell carcinoma of the oropharynx is a rare and newly described variant that is associated with aggressive clinical behavior and poor outcomes. To date, fewer than 2 dozen reports of this entity exist in the literature, and there is no discussion of cytopathologic features. This article reports 6 cases and discusses the salient cytomorphologic findings, ancillary studies, and challenges when this entity is encountered. METHODS: Anatomic pathology archives were searched to identify patients with a diagnosis of HPV-related small cell carcinoma of the oropharynx. Medical records were reviewed to document the following: age, sex, smoking status, other relevant clinical history, primary location, treatment, and clinical outcome. Both p16 and high-risk HPV in situ hybridization (ISH) studies were positive in at least 1 specimen from each patient. The pathologic diagnoses, cytomorphologic characteristics, immunocytochemical stains, and HPV ISH studies were reviewed and recorded for all available cases. RESULTS: Six patients with 11 cytopathology specimens of HPV-related small cell carcinoma of the oropharynx were identified. The mean age was 61.3 years, and all patients died with widely metastatic disease (mean, 23 months; range, 12-48 months). Mixed small cell carcinoma and SqCC components were present in half of the cases. CONCLUSIONS: The identification of a small cell component can be reliably performed with cytology preparations and is crucial because this (and not the HPV status) determines the prognosis.


Assuntos
Carcinoma de Células Pequenas/patologia , Neoplasias Orofaríngeas/patologia , Papillomaviridae , Infecções por Papillomavirus/patologia , Doenças Raras/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/virologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/mortalidade , Prognóstico , Doenças Raras/mortalidade , Doenças Raras/virologia
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