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1.
Bull Cancer ; 108(1): 80-89, 2021 Jan.
Artigo em Francês | MEDLINE | ID: mdl-33423780

RESUMO

Despite its status as a rare disease, the incidence of the squamous cell carcinoma of the anus (SCCA) is surging, especially in its metastatic form. In addition, the prognosis of initially localized diseases has not substantially changed since the 1970s with a recurrence rate of between 25-40 % after the chemoradiotherapy. The updated data from 115 patients included in the Epitopes-HPV01 and Epitopes-HPV02 trials, confirm the modified regimen of DCF (mDCF) as the treatment of choice for patients with advanced SCCA given the rate of sustained remissions and complete molecular responses observed. The carboplatin-paclitaxel regimen may be considered as an option for patients with contraindication to cisplatin or 5-FU. In chemo-refractory patients, the efficacy of anti-PD-1/PD-L1 in monotherapy is limited and only brings benefit to 10-20 % of patients, and its use cannot be generalized in the absence of an association potentiating its effectiveness. In order to better understand the immunological parameters associated with advanced SCCA, an analysis of peripheral immune responses was carried out in the Epitopes-HPV01 and 02 trials. It demonstrated the key role of CD4 Th1 specific responses of telomerase and M-MDSC as main prognostic factors for the therapeutic efficacy of DCF. Numerous combination trials are currently underway or will soon begin in localized SCCA, as well as in the first and second-line in the advanced stage. Finally, the detection of circulating tumor DNA of HPV oncoprotein E6 and E7 (HPVtc), especially by the "digital droplet PCR" technique, is highly sensitive and specific, and can be used in daily practice.


Assuntos
Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Alphapapillomavirus/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/imunologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/virologia , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Cisplatino/efeitos adversos , Ensaios Clínicos como Assunto , Contraindicações de Medicamentos , DNA Viral/análise , Fluoruracila/efeitos adversos , Humanos , Imunidade Celular , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Telomerase/imunologia
2.
Adv Exp Med Biol ; 1287: 105-122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034029

RESUMO

The NOTCH pathway is critical for the development of many cell types including the squamous epithelium lining of cutaneous and mucosal surfaces. In genetically engineered mouse models, Notch1 acts as one of the first steps to commit basal keratinocytes to terminally differentiate. Similarly, in human head and neck squamous cell cancers (HNSCCs), NOTCH1 is often lost consistent with its essential tumor-suppressive role for initiating keratinocyte differentiation. However, constitutive NOTCH1 activity in the epithelium results in expansion of the spinous keratinocyte layers and impaired terminal differentiation is consistent with the role of NOTCH1 as an oncogene in other cancers, especially in T-cell acute lymphoblastic leukemia. We have previously observed that NOTCH1 plays a dual role as both a tumor suppressor and oncogene, depending on the mutational context of the tumor. Namely, gain or loss or NOTCH1 activity promotes the development of human papillomavirus (HPV)-associated cancers. The additional HPV oncogenes likely disrupt the tumor-suppressive activities of NOTCH and enable the oncogenic pathways activated by NOTCH to promote tumor growth. In this review, we detail the role of NOTCH pathway in head and neck cancers with a focus on HPV-associated cancers.


Assuntos
Carcinogênese , Neoplasias Bucais/metabolismo , Neoplasias Bucais/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Humanos , Infecções por Papillomavirus/virologia
3.
Am J Surg Pathol ; 45(1): 108-118, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32868526

RESUMO

Sinonasal squamous cell carcinoma (SNSCC) is sometimes associated with high-risk human papillomavirus (HR-HPV) infection and inverted sinonasal papilloma or oncocytic sinonasal papilloma. Frequent mutations of EGFR and KRAS are reported in inverted sinonasal papilloma-related sinonasal squamous cell carcinoma (ISP-SCC) and oncocytic sinonasal papilloma-related SNSCC, respectively. Here, we attempted to determine the prevalence and the prognostic significances of these alterations in SNSCC. We retrospectively collected 146 SNSCCs, including 14 ISP-SCCs, and comprehensively analyzed the HR-HPV infection by human papillomavirus (HPV)-RNA in situ hybridization, EGFR gene copy number gain (CNG) by chromogenic in situ hybridization, and gene mutations in EGFR and KRAS by Sanger sequencing. HR-HPV was detected in 11 cases (7.5%), whereas all 14 ISP-SCCs were negative. EGFR mutations were present in 21 (14.7%) of 143 SNSCCs, including 13/14 (92.9%) ISP-SCCs and 8/129 (6.2%) non-ISP-SCCs (P<0.0001). The majority of EGFR mutations were exon 20 insertions, with the remainder composed of deletions and single-nucleotide substitutions in exons 19 and 20. All of 142 SNSCCs harbored no KRAS mutation. EGFR CNG was detected in 41 (28.1%) of 146 SNSCCs; all of them were HPV negative and 3 had EGFR mutations. Collectively, EGFR mutation, EGFR CNG, and HR-HPV were essentially mutually exclusive, and each subgroup had distinct clinicopathologic features. The HPV-negative/EGFR-mutant group, the HPV-negative/EGFR CNG-positive group, and the triple-negative group had significantly worse prognoses than the HPV-positive group (P=0.0265, 0.0264, and 0.0394, respectively). In conclusion, EGFR mutation may play a pathogenetically important role in some populations of SNSCCs, especially ISP-SCCs. The molecular subclassification of SNSCCs may contribute to prognostic prediction and molecular-targeted precision medicine.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virologia , Infecções por Papillomavirus/complicações , Neoplasias dos Seios Paranasais/genética , Neoplasias dos Seios Paranasais/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Variações do Número de Cópias de DNA , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos
4.
Crit Rev Oncol Hematol ; 156: 103116, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33115701

RESUMO

OBJECTIVES: to provide accurate information about the global prevalence of human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (OPSCC). MATERIAL AND METHODS: a systematic review was performed using three main electronic databases. Studies were independently assessed by two reviewers based on established eligibility criteria, to identify the prevalence of HPV-driven OPSCC following criteria defined by the American Society of Clinical Oncology. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Statistical software MedCalc was used to perform meta-analyses. RESULTS: from 2215 records found, 15 were included, reporting data from 6009 patients (time period range: 1980-2016), distributed in 11 countries. Eleven studies were considered as presenting low risk, and four as moderate risk of bias. Using proportion meta-analysis, pooled prevalence of HPV-driven OPSCC was 44.8 % (95 %CI: 36.4-53.5 %; i2 = 97.6 %), with the highest rates in New Zealand (74.5 %; 95 %CI: 60.9-85.3 %), and the lowest in Brazil (11.1 %; 95 %CI: 4.5-21.5 %). HPV prevalence was similar between males (45.7 %; 95 %CI: 36.5-55.0 %; i2 = 96.4 %) and females (42.2 %; 95 %CI: 34.3-50.5 %; i2 = 85.4 %). Mean/median age ranged from 59.1-67.1 years in the HPV-negative group, and from 55.7-63.5 years in the HPV-positive group. There was an overall discordance between testing by p16 (49.4 %; 95 %CI, 38.2-60.5 %; i2 = 96.2 %) and p16+ISH/PCR (44.7 %; 95 %CI, 33.5-56.2 %; i2 = 96.4 %). CONCLUSION: Overall pooled prevalence of HPV-driven OPSCC was approximately 45 %, with similar distribution among males and females. Double p16/HPV-DNA/RNA testing may be considered to increase specificity and prognostic accuracy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Papillomaviridae , Infecções por Papillomavirus , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Prevalência
5.
Anticancer Res ; 40(11): 6355-6366, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109573

RESUMO

BACKGROUND/AIM: p16 and PTEN are tumor suppressor genes. Loss of these molecules in oral squamous cell carcinoma (OSCC) has been studied worldwide. In this study, we explored whether p16 cooperates with inactive PTEN during the pathogenesis of OSCC, especially in regard to tumor aggressiveness and proliferation. MATERIALS AND METHODS: Immunocytochemistry and western blot analysis were used to examine the levels of p16 and PTEN. Sequencing analysis was performed to identify mutations in the PTEN gene and HPV infection. Fluorescence in situ hybridization was used to examine the presence of the PTEN locus. RESULTS: PTEN analysis showed high positivity in T4 samples. HPV-positive tumors correlated with tabagism, tumor size 3 and 4, disease stages 3 and 4, presence of lymph node metastasis (N1) and poor differentiation. Immunoexpression of p16 was strongly correlated with the presence of HPV. CONCLUSION: PTEN demonstrated a higher reactivity in advanced disease stages and p16 was strongly associated with HPV. Viral presence decreases tumor aggressiveness. Patients with advanced stage lesions demonstrated lower survival rate.


Assuntos
Carcinoma de Células Escamosas/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias Bucais/genética , PTEN Fosfo-Hidrolase/genética , Adulto , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Hibridização in Situ Fluorescente , Perda de Heterozigosidade/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia
6.
Adv Exp Med Biol ; 1268: 195-209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918220

RESUMO

Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 220 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood.From patients with the rare genetic disorder epidermodysplasia verruciformis (EV) and animal models, evidence is accumulating that cutaneous PV of genus ß synergize with ultraviolet (UV) radiation in the development of cutaneous squamous cell carcinoma (cSCC). In 2009, the International Agency for Research on Cancer (IARC) classified the genus ß-HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. Epidemiological and biological studies indicate that genus ß-PV infection may also play a role in UV-mediated skin carcinogenesis in non-EV patients. However, they rather act at early stages of carcinogenesis and become dispensable for the maintenance of the malignant phenotype, compatible with a "hit-and-run" mechanism.This chapter will give an overview on genus ß-PV infections and discuss similarities and differences of cutaneous and genus α mucosal high-risk HPV in epithelial carcinogenesis.


Assuntos
Papillomaviridae/patogenicidade , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/virologia , Animais , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/virologia , Epidermodisplasia Verruciforme/etiologia , Epidermodisplasia Verruciforme/virologia , Humanos , Raios Ultravioleta/efeitos adversos
7.
Praxis (Bern 1994) ; 109(9): 697-703, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32635845

RESUMO

Update for Diagnosis and Management of HPV-Driven Oropharyngeal Cancer Abstract. In the past decades, an increasing incidence of oropharyngeal squamous cell cancer could be observed. More than twenty years ago, a correlation between a pharyngeal Human papillomavirus high-risk type infection and the development of oropharyngeal cancer has been suspected. Especially younger patients without the former risk factors smoking and alcohol have a higher prevalence for this cancer type. HPV-associated cancer is developing in the lymphatic tissue of the tonsils and the base of the tongue. HPV-driven tumors can be defined as a clinical and morphologic distinct tumor entity with a significantly better prognosis compared to tumors based on smoking and alcohol consumption. They are demonstrating a clearly better treatment response irrespective of the treatment modality. The tumor development is assumed to be comparable to cervical cancer, probably through a step-wise process from dysplasia to invasive cancer. In the pharynx, no HPV-associated precursor lesions have been detected so far. Therefore, Screening program proven to be very successful in the cervix have not could not have been implemented so far. The reduction of HPV-associated tumor burden in the cervix is likely to be compensated by the rising number of HPV-driven oropharyngeal cancer. P16 as a surrogate marker for HPV has been implemented in the 8th edition of the TNM classification for oropharyngeal cancer. A worldwide accepted definition of an HPV-driven tumor is lacking so far. P16 immunhistochemistry or HPV-DNA detection by PCR as single markers have an insufficient sensitivity and specificity. A combination of both markers demonstrates a higher accuracy compared to the gold standard RNA. Antibodies to HPV oncoproteins are reliable diagnostic and prognostic markers that could in the future possibly serve for early tumor detection.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Biomarcadores Tumorais , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Humanos , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/terapia , Prognóstico
8.
HNO ; 68(9): 688-694, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32638060

RESUMO

The incidence of human papillomavirus (HPV)-positive oropharyngeal carcinomas is increasing worldwide. Due to a markedly different response to treatment compared to HPV-negative oropharyngeal carcinomas, determining the ideal therapeutic approach can be challenging. Particularly in never-smokers, HPV-positive oropharyngeal carcinomas respond well to primary radiation therapy; at the same time recent studies indicate comparable survival after primary surgery. For stage I tumors according to TNM­8, retrospective analyses show very good oncologic outcomes after surgery alone, and no added benefit of adjuvant radio- or chemotherapy. Results of prospective treatment deintensification trials are expected in the coming years. Minimally invasive transoral surgical approaches for selected oropharyngeal cancers can improve preservation of postoperative function and quality of life. For both HPV-positive and HPV-negative oropharyngeal carcinomas, salvage surgery is the treatment of choice for resectable recurrent locoregional disease and resectable distant metastases.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Procedimentos Cirúrgicos Robóticos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/virologia , Humanos , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Terapia de Salvação
9.
Life Sci ; 256: 118026, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32615187

RESUMO

AIM: We aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection. MATERIALS AND METHODS: Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: We examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated. CONCLUSION: Deregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.


Assuntos
Genes de Cadeia Pesada de Imunoglobulina/genética , Genes MHC da Classe II/genética , Infecções por Papillomavirus/complicações , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Regulação para Baixo , Matriz Extracelular/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Estadiamento de Neoplasias , Infecções por Papillomavirus/genética , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia , Transcriptoma , Regulação para Cima , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
10.
Am J Surg Pathol ; 44(9): 1184-1191, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32496434

RESUMO

Tumor cell expression of major histocompatibility complex (MHC) class I is required for antigen presentation and adaptive immune recognition. Absent or diminished MHC class I expression is thought to contribute to immunotherapeutic resistance in some epithelial tumors but has not been previously studied in cervical and vulvar carcinoma. Given that anti-programmed cell death 1 (PD-1) checkpoint inhibition is deployed for programmed cell death ligand 1 (PD-L1)-positive recurrent and metastatic cervical squamous carcinomas, identifying tumors with loss of MHC class I is of clinical interest to optimize the selection of immunotherapeutic candidates. Immunohistochemistry for PD-L1 and MHC class I combined A, B, and C heavy chains (MHC class I) was assessed in 58 human papillomavirus-associated cervical and vulvar lesions, including 27 squamous intraepithelial lesions (SILs) and 31 invasive squamous cell carcinoma (SCC). Although 84% of SCC and 22% of SIL were PD-L1-positive, 35.5% (11/31) of SCC and 18.5% (5/27) of SIL also showed clonal or complete loss of MHC class I. Loss of MHC class I expression was more common in PD-L1-positive (10/26, 38%) versus PD-L1-negative SCC (1/5, 20%). In summary, over one third of human papillomavirus-associated cervical and vulvar SCC show clonal or complete loss of MHC class I expression, including many PD-L1-positive cases. This suggests that the efficacy of checkpoint inhibitors targeting the PD-1/PD-L1 axis may be limited in a subset of cervical and vulvar squamous neoplasms due to an impaired ability to engage with the adaptive immune system related to loss of MHC class I expression.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Escamosas/virologia , Resistencia a Medicamentos Antineoplásicos , Antígenos de Histocompatibilidade Classe I/imunologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/virologia , Neoplasias Vulvares/virologia , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Regulação para Baixo , Feminino , Interações Hospedeiro-Patógeno , Humanos , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Lesões Intraepiteliais Escamosas Cervicais/tratamento farmacológico , Lesões Intraepiteliais Escamosas Cervicais/imunologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias Vulvares/tratamento farmacológico , Neoplasias Vulvares/imunologia , Neoplasias Vulvares/patologia
11.
Rev. otorrinolaringol. cir. cabeza cuello ; 80(2): 184-192, jun. 2020.
Artigo em Espanhol | LILACS | ID: biblio-1115834

RESUMO

La recurrencia de carcinoma de células escamosas orofaríngeo (CCEOF) se asocia a mal pronóstico, particularmente en recurrencias en etapa avanzada. La cirugía en el contexto de rescate es más complicada por el tratamiento oncológico del tumor primario, por lo tanto, tiene un mayor riesgo de complicaciones y estadía hospitalaria. Sin embargo, la cirugía de rescate es la mejor oportunidad del paciente como tratamiento curativo y para supervivencia a largo plazo. La población de pacientes que reciben tratamiento para CCEOF ha cambiado en la última década, se ha reconocido que la incidencia de virus papiloma humano (VPH) asociado a CCEOF ha generado el gran aumento de CCEOF y el cambio asociado en las características de la población de pacientes, ahora los pacientes son más jóvenes y tienen menos comorbilidades. Con el aumento exponencial en la incidencia de CCEOF, la necesidad de cirugía de rescate en CCEOF podría verse en aumento. En vista del aumento de la incidencia de casos con carcinoma escamoso de orofaringe y su importante relación con el VPH, esta revisión se enfoca en la supervivencia tras cirugía de rescate con intención curativa y evaluar si con los avances en su tratamiento ha mejorado su pronóstico.


Recurrence of oropharyngeal squamous cell carcinoma (OPSCC) is associated with poor prognosis, particularly in advanced stage recurrences. Salvage surgery is complicated by previous oncological treatment of the primary tumor, therefore, it has a higher risk of complications and hospital stay. However, salvage surgery is the patient's best opportunity as a curative treatment and for long-term survival. The population of patients receiving treatment for OPSCC has changed in the last decade, it has been recognized that the incidence of human papilloma virus (HPV) associated OPSCC has generated an increase of OPSCC and changes in the epidemiology of the patient population, with younger patients and with less comorbidities. With the exponential increase in the incidence of OPSCC, the need for salvage surgery in OPSCC could increase in the future. In view of the increase in the incidence of cases with squamous oropharyngeal carcinoma and its relationship with HPV, this review focuses on survival after salvage surgery with curative intent and assessing whether the progress in its treatment has improved its prognosis.


Assuntos
Humanos , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Recidiva Local de Neoplasia , Papillomaviridae , Complicações Pós-Operatórias , Prognóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/virologia , Taxa de Sobrevida , Terapia de Salvação , Seleção de Pacientes , Futilidade Médica , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/virologia
12.
PLoS One ; 15(5): e0232871, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407339

RESUMO

Human papillomavirus (HPV) is responsible for the rise in the incidence of cancer in the oropharynx, tonsils, and base of the tongue (i.e., HPV-related subsites). HPV triggered the changes in the epidemiology of oropharyngeal and oral cavity cancer (OPC/OCC) in Asia, Europe, North America, and Oceania. Hence, the incidence of cancer in HPV-related subsites is augmenting, while that in other HPV-unrelated subsites is decreasing. In South America, although the incidence of HPV-positive tumors has gradually increased, there is an atypically low prevalence of HPV in people with OPC/OCC. To clarify whether this dramatic shift in incidence trends also occurred in this population, we estimated the burden of HPV on the incidence trends of OPCs/OCCs in São Paulo city in Brazil. In this population-based study, we categorized OPCs/OCCs by HPV-related and HPV-unrelated subsites. We used Poisson regression to assess the age-standardized incidence rates (ASRs) stratified by sex and age groups, as well as to examine the age-period-cohort effects. There were 15,391 cases of OPCs/OCCs diagnosed in HPV-related (n = 5,898; 38.3%) and HPV-unrelated (n = 9,493; 61.7%) subsites. Overall, the ASRs decreased for most subsites, for both sexes and for all age groups, except for HPV-related OPC/OCC in young males and females, which increased by 3.8% and 8.6% per year, respectively. In the birth-cohort-effect analysis, we identified an increasing risk for HPV-related OPC/OCC in both sexes in recent birth cohorts; however, this risk was sharply decreased in HPV-unrelated subsites. Our data demonstrate an emerging risk for HPV-related OPC/OCC in young people, which supports prophylactic HPV vaccination in this group.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias Bucais/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Brasil/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Fatores Sexuais , Adulto Jovem
13.
J Clin Pathol ; 73(11): 754-757, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32366599

RESUMO

In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pathologists can be exposed to infection handling surgical specimens. Guidelines related to safety procedures in the laboratory have been released. However, there is a lack of studies performed on biopsy and surgical resection specimens. Here we report the detection of SARS-CoV-2 in formalin-fixed paraffin-embedded samples from surgical resection of tongue squamous cell carcinoma of a patient who developed COVID-19 postsurgery. RNA of SARS-CoV-2 strain was detected in the tumour and the normal submandibular gland samples using real-time PCR-based assay. No viral RNA was found in metastatic and reactive lymph nodes. We demonstrated that SARS-CoV-2 RNA can be detected in routine histopathological samples even before COVID-19 disease development. These findings may give important information on the possible sites of infection or virus reservoir, and highlight the necessity of proper handling and fixation before sample processing.


Assuntos
Betacoronavirus/isolamento & purificação , Carcinoma de Células Escamosas/cirurgia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Preservação de Tecido/métodos , Neoplasias da Língua/cirurgia , Betacoronavirus/genética , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/virologia , Fixadores , Formaldeído , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Inclusão em Parafina , Pneumonia Viral/etiologia , Pneumonia Viral/virologia , Complicações Pós-Operatórias/virologia , RNA Viral/análise , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fixação de Tecidos/métodos , Neoplasias da Língua/complicações , Neoplasias da Língua/patologia , Neoplasias da Língua/virologia
15.
Eur J Cancer ; 134: 52-59, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32460181

RESUMO

BACKGROUND: The objectives of this study were to investigate the incidence of high-risk genotypes of human papillomavirus (HPV) in tumours of patients with oropharyngeal squamous cell carcinoma (OPSCC) during an 18-year period in Eastern Denmark. METHODS: In this population-based, consecutive, semi-national registry study, all patients diagnosed with OPSCC from 2000 to 2017 in Eastern Denmark were evaluated at head and neck oncological departments at public university hospitals. Analyses included tumour characteristics (HPV-positive [HPV+] versus HPV-negative [HPV-]), age-adjusted incidence rates (AAIRs), average annual percentage change (AAPC) of OPSCC, and patient demographics. All HPV+ cases from 2011 to 2017 were genotyped. RESULTS: In total, 55% of 2169 OPSCC cases were HPV+. HPV16, HPV33, HPV35 or other types were found in 86%, 7.4%, 3.4% and 3.2% of cases, respectively. The AAIR per 100,000 of all OPSCCs was 1.8 in 2000, which increased to 5.1 in 2017 (HPV+: threefold increase, HPV-: twofold increase). The AAPC from 2000 to 2017 increased by 7% (HPV+ increased by 10% and HPV- by 4%). The median age at diagnosis for all OPSCC cases increased during the 18-year study period (HPV+: 58-61 years, p < 0.001; HPV-: 60-65 years, p < 0.001). CONCLUSION: We report a threefold increase in OPSCC incidence during the 18-year observation period and a significant increase in median age at diagnosis. Over 93% of HPV genotypes in HPV+ OPSCC are included in current HPV vaccines except for HPV35 (4%). HPV vaccination of both sexes is advised to halt this emerging cancer epidemic.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Epidemias/estatística & dados numéricos , Neoplasias Orofaríngeas/epidemiologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/virologia , Prognóstico
16.
Sci Rep ; 10(1): 7863, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398763

RESUMO

Equine penile squamous cell carcinoma (EpSCC) is a relatively common cutaneous neoplasm with a poor prognosis. In this study, we aimed to determine the protein expression and colocalisation of FRA1, c-Myc, Cyclin D1, and MMP7 in normal (NT), tumour (T), hyperplastic epidermis and/or squamous papilloma (Hyp/Pap), poorly-differentiated (PDSCC), or well-differentiated (WDSCC) EpSCC using a tissue array approach. Further objectives were to correlate protein expression to (i) levels of inflammation, using a convolutional neural network (ii) equine papillomavirus 2 (EcPV2) infection, detected using PCR amplification. We found an increase in expression of FRA1 in EpSCC compared to NT samples. c-Myc expression was higher in Hyp/Pap and WDSCC but not PDSCC whereas MMP7 was reduced in WDSCC compared with NT. There was a significant increase in the global intersection coefficient (GIC) of FRA1 with MMP7, c-Myc, and Cyclin D1 in EpSCC. Conversely, GIC for MMP7 with c-Myc was reduced in EpSCC tissue. Inflammation was positively associated with EcPV2 infection in both NT and EpSCC but not Hyp/Pap. Changes in protein expression could be correlated with EcPV2 for Cyclin D1 and c-Myc. Our results evaluate novel biomarkers of EpSCC and a putative correlation between the expression of biomarkers, EcPV2 infection and inflammation.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/genética , Neoplasias Penianas/genética , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/virologia , Ciclina D1/genética , Ciclina D1/metabolismo , Cavalos , Masculino , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 7 da Matriz/metabolismo , Papillomaviridae/fisiologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Neoplasias Penianas/diagnóstico , Neoplasias Penianas/virologia , Ligação Proteica , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Curva ROC , Análise Serial de Tecidos/métodos
17.
Med. oral patol. oral cir. bucal (Internet) ; 25(3): e425-e430, mayo 2020. tab
Artigo em Inglês | IBECS | ID: ibc-196332

RESUMO

BACKGROUND: The Human Papillomavirus (HPV) has different strategies for persist in the cells. This characteristic has led us to consider the presence of the virus in tissues of the oral cavity that had no clinical signs of infection. The aim of this study was to detect the presence of DNA-HPV at multiple sites of the oral cavity. MATERIAL AND METHODS: A case-control study was designed: Oral Squamous Carcinoma Group (OSCG), healthy n=72 and Control Group (CG), n=72, healthy volunteers paired by sex and age with OSCG. Four samples were taken from OSCG: saliva, biopsy, brush scraping of lesion and contralateral healthy side. In CG a saliva sample and a scratch of the posterior border of tongue were collected. HPV was detected by PCR using Bioneer Accuprep genomic DNA Extraction kit, and consensus primers MY09 and MY11. Chi square test was applied. RESULTS: 432 samples were obtained from 144 individuals. DNA-HPV was detected in 30 (42%) of OSCG subjects and 3 (4%) of CG. Two or more positive samples were obtained in 67% of the OSCG, 67% in saliva and 60% in biopsy; in CG 100% of the individuals were positive in the two samples. CONCLUSIONS: HPV is frequently present in oral cavity as a multifocal infection, even without the presence of clinical lesions


No disponible


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Boca/virologia , Papillomaviridae/isolamento & purificação , DNA Viral/isolamento & purificação , Carcinoma de Células Escamosas/virologia , Neoplasias Bucais/virologia , Infecções por Papillomavirus/virologia , Estudos de Casos e Controles , Saliva/virologia , Fatores de Risco , Reação em Cadeia da Polimerase
18.
Med. oral patol. oral cir. bucal (Internet) ; 25(3): e431-e438, mayo 2020. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-196333

RESUMO

BACKGROUND: Although new digital pathology tools have improved the positive cell quantification, there is a heterogeneity of the quantification methods in the literature. The aim of this study was to evaluate and propose a novel dendritic cells quantification method in squamous cell carcinoma comparing it with a conventional quantification method. MATERIAL AND METHODS: Twenty-six squamous cell carcinomas HIV-positive cases affecting the oropharynx, lips and oral cavity were selected. Immunohistochemistry for CD1a, CD83, and CD207 was performed. The immunohistochemical stains were evaluated by automated examination using a positive pixel count algorithm. A conventional quantification method (unspecific area method; UA) and a novel method (specific area method; SA) were performed obtaining the corresponding density of positive dendritic cells for the intratumoral and peritumoral regions. The Mann-Whitney U test was used to verify the influence of the quantification methods on the positive cell counting according to the evaluated regions. Data were subjected to the ANOVA and Student's t-test to verify the influence of the tumour location, stage, histological grade, and amount of inflammation on the dendritic cells density counting. RESULTS: The cell quantification method affected the dendritic cells counting independently of the evaluated region (P-value < 0.05). Significant differences between methods were also observed according to the tumour features evaluations. CONCLUSIONS: The positive cell quantification method influences the dendritic cells density results. Unlike the conventional method (UA method), the novel SA method avoids non-target areas included in the hotspots improving the reliability and reproducibility of the density cell quantification


No disponible


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Infecções por HIV/patologia , Células Dendríticas/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Neoplasias Orofaríngeas/patologia , Infecções por HIV/virologia , Células Dendríticas/virologia , Inclusão em Parafina , Imuno-Histoquímica/métodos , Estatísticas não Paramétricas , Análise de Variância , Carcinoma de Células Escamosas/virologia , Neoplasias Bucais/virologia , Neoplasias Orofaríngeas/virologia
19.
Laryngoscope ; 130(8): 1961-1966, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32293733

RESUMO

OBJECTIVE: To determine the prognostic significance of smoking in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) when considering American Joint Committee on Cancer eighth edition (AJCC-8) stage. STUDY DESIGN: Retrospective cohort study. METHODS: Three hundred seventeen HPV-positive OPSCC patients with known AJCC-8 stage and smoking status (<10 or ≥10 pack-years) seen at a tertiary center from 1997 to 2017 were studied. We used the Kaplan-Meier method to compare 5-year overall survival (OS) by smoking status and by clinical AJCC-8 stage and smoking status combined. Hazard ratios (HRs) were estimated with Cox proportional hazard regression for the independent effects of smoking and AJCC-8 stage. We also studied pathologic stage and estimated the combined effects of smoking and clinical stage. RESULTS: The ≥10 pack-years smokers had worse 5-year OS than <10 pack-years smokers (93.6%; 95% confidence interval (CI): 89.7-97.8 vs. 82.3%; 95% CI: 76.0%-89.1%). When stratified by AJCC-8 clinical stage, only stage I <10 pack-years smokers (98.7%; 95% CI: 96.3%-100.0%) had significantly better 5-year OS than their ≥10 pack-years (84.8%; 95% CI: 76.4%-94.1%) counterparts. In a multivariable analysis, ≥10 pack-years smoking was associated with increased hazard of death when adjusting for AJCC-8 clinical (HR: 2.52; 95% CI: 1.16-5.46) and pathologic (HR: 5.21; 95% CI: 1.47-18.5) stage. In both analyses, stage III patients demonstrated worse survival than stage I, and smoking had greater impact at lower stages. CONCLUSIONS: Smoking is a negative prognosticator in HPV-positive OPSCC and interacts with AJCC-8 clinical stage. It is important to understand the impact of smoking in HPV-positive disease when considering treatment plans and deintensification trials. LEVEL OF EVIDENCE: 2b Laryngoscope, 130: 1961-1966, 2020.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Fumar/efeitos adversos , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos
20.
Cancer Immunol Immunother ; 69(8): 1615-1626, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32314041

RESUMO

BACKGROUND: The etiological role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is confirmed. However, the role of other oncoviruses in OPSCC is unknown. MATERIALS AND METHODS: A total of 158 consecutive OPSCC patients treated with curative intent were included. DNA extracted from tumor sections was used to detect Epstein-Barr virus (EBV), HPV, and the following polyomaviruses: John Cunningham virus (JCV), Simian virus 40 (SV40), and BK virus (BKV) with PCR. In addition, p16 expression was studied by immunohistochemistry, and EBV-encoded small RNA (EBER) transcripts were localized by in situ hybridization. The effect of viral status on overall survival (OS) and disease-free survival (DFS) was analyzed. RESULTS: A total of 94/158 samples (59.5%) were HPV-positive, 29.1% contained BKV DNA, 20.3% EBV DNA, 13.9% JCV DNA, and 0.6% SV40 DNA. EBER was expressed only in stromal lymphocytes adjacent to the tumor and correlated with HPV positivity (p = 0.026). p16 expression associated only with HPV. None of the three polyomaviruses had an impact on survival. Patients with EBER-positive but HPV-negative OPSCC had significantly poorer OS and DFS than those with HPV-positive OPSCC and slightly worse prognosis compared with the patients with EBER-negative and HPV-negative OPSCC. CONCLUSION: Polyomaviruses are detectable in OPSCC but seem to have no impact on survival, whereas HPV was the strongest viral prognostic factor. EBER expression, as a sign of latent EBV infection, may have prognostic impact among patients with HPV-negative OPSCC. EBER analysis may identify a new subgroup of OPSCCs unrelated to HPV.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Neoplasias Orofaríngeas/virologia , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/metabolismo , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Polyomavirus/isolamento & purificação , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/virologia , Prognóstico , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/virologia
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