Orally Bioavailable Proteolysis-Targeting Chimeras: An Innovative Approach in the Golden Era of Discovering Small-Molecule Cancer Drugs.

Proteolysis-targeting chimeras (PROTACs) are an emerging therapeutic modality that show promise to open a target space not accessible to conventional small molecules via a degradation-based mechanism. PROTAC degraders, due to their bifunctional nature, which is categorized as 'beyond the Rule of Five', have gained attention as a distinctive therapeutic approach for oral administration in clinical settings. However, the development of PROTACs with adequate oral bioavailability remains a significant hurdle, largely due to their large size and less than ideal physical and chemical properties. This review encapsulates the latest advancements in orally delivered PROTACs that have entered clinical evaluation as well as developments highlighted in recent scholarly articles. The insights and methodologies elaborated upon in this review could be instrumental in supporting the discovery and refinement of novel PROTAC degraders aimed at the treatment of various human cancers.

A modified pull-through approach with a pedicled bone flap for oral and oropharyngeal cancer resection: a feasibility study.

PURPOSE: Compromised swallowing, speaking, and local complications are the major disadvantages of established approaches to the posterior tongue and oropharynx. The mandibular split involves an esthetically unpleasant bipartition of the lower lip and is prone to bony non-union or sequestration. The conventional pull-through technique on the other hand lacks the secure reattachment of the lingually released soft tissues. METHODS: The feasibility of a new modified pull-through approach was tested on three anatomical specimens. CAD/CAM cutting guides were used to design a retentive bone flap to properly refixate the genioglossus and geniohyoid muscles after the procedure. The radiographic assessment and treatment planning was performed on 12 cadavers. The entire procedure was tested surgically via dissection in three of those cases. This procedure was then applied in a clinical case. RESULTS: Precise repositioning and dynamic compression of bony segments was possible reproducibly and without injury to adjacent structures. In all dissected cases, a median lingual foramen was found and in two cases vessels entering it could be dissected Radiologic anatomical landmarks were sufficient in all 12 cases to perform the clinical planning procedure. Clinically, the osteotomized segment demonstrated good blood supply and plateless repositioning was verified postoperatively via cone beam scan. CONCLUSION: The method presented is safe and easy to perform. Individual cutting guides improve the safety and accuracy of the procedure, potentially eliminating the need for osteosynthesis. We provide the anatomical and radiologic basis for clinical evaluation of this pedicled bone flap procedure and present the clinical application of this modified pull-through approach.

Epidemiological, clinical, and prognostic analysis of oral squamous cell carcinoma diagnosed and treated in a single hospital in Galicia (Spain): a retrospective study with 5-year follow-up / Análisis epidemiológico, clínico y pronóstico del carcinoma oral de células escamosas diagnosticado y tratado en un único hospital de Galicia (España): un estudio retrospectivo con un seguimiento de 5 años

Background: Oral cancer is a common neoplasm worldwide, mostly corresponding to squamous cell carcinoma(OSCC). Unfortunately, its overall prognosis remains poor, with no improvement in recent decades. In this study,we have analysed the epidemiological, clinical, and prognostic characteristics of OSCC on patients of a specificSpanish region (Galicia), in order to improve its prognosis and apply effective preventive and early diagnosismeasures.Material and Methods: We retrospectively analysed 243 cases of OSCC, diagnosed and treated in a single hospitalcentre in Galicia between 2010 and 2015 (minimum of 5 years of evolution). Overall and specific survival werecalculated (Kaplan-Meier) and associated variables were identified (log rank test and Cox regression).Results: The mean age of the patients was 67 years, with the majority being male (69.5%), smokers (45.9%) andalcohol consumers (58.6%), who lived in non-urban areas (79.4%). Cases diagnosed at advanced stages entailedthe 48.1% of the sample, and 38.7% of cases relapsed. The 5-year overall and disease-specific survival rates were39.9% and 46.1%, respectively. Patients who consumed tobacco and alcohol had a worse prognosis. OSCC casesreferred to hospital by specialist dentists had a better prognosis, as those who were previously diagnosed with anoral potentially malignant oral disorder (OPMD) or received dental care during OSCC treatmen. Conclusions: In view of these findings, we conclude that OSCC in Galicia (Spain) still has a very poor overall prog-nosis, which is mainly related to the advanced age of the patients and the late diagnosis. Our study highlights thebetter survival of OSCC in relation to the referring health professional, the presence of a previous OPMD and thedental care after diagnosis. This demonstrates the importance of dentistry as a health profession involved in the earlydiagnosis and multidisciplinary management of this malignant neoplasm.(AU)

Estudo multicêntrico das neoplasias malignas de boca em pacientes pediátricos e adolescentes / Multicentric study of head and neck neoplasms in pediatric and adolescent patients

O objetivo deste estudo foi descrever as características clínicas, demográficas e histopatológicas e de distribuição das neoplasias malignas de boca em pacientes pediátricos e adolescentes de diversos centros de diagnóstico. Foi realizado um levantamento de dados em prontuários clínicos de pacientes com idade menor ou igual a 19 anos portadores de neoplasias malignas de boca diagnosticados no ICT/SJC, Departamento de Patologia Bucal (UFPb), Fundação Centro de Controle de Oncologia do Estado do Amazonas (FCecon-Am) e Departamento de Patologia e Diagnóstico Oral (UFRJ). Esta coleta de dados foi realizada por meio de uma análise retrospectiva dos prontuários médicos dos pacientes atendidos em um período de 30 anos (1986-2016). No período de 30 anos, 37 neoplasias malignas em boca foram diagnosticadas em 4 diferentes centros no Brasil. A média de idade dos pacientes no momento do diagnóstico foi de 12,2 anos, sendo o sexo feminino e a raça branca os mais acometidos. No geral, os sarcomas foram os mais frequentes (37,9%), seguido dos linfomas (27%). A mandíbula foi a região mais acometida (37,8%), seguido da maxila (32,4%), totalizando mais de 70% dos casos (AU)

The objective of this study was to describe the clinical, demographic and histopathological characteristics and distribution of oral malignant neoplasms in pediatric and adolescent patients from different diagnostic centers. A data collection was carried out in clinical records of patients aged less than or equal to 19 years with malignant neoplasms of the mouth diagnosed at the ICT/SJC, Department of Oral Pathology (UFPb), Fundação Centro de Controle de Oncologia do Estado do Amazonas (FCecon-Am) and Department of Oral Pathology and Diagnosis (UFRJ). This data collection was carried out through a retrospective analysis of the medical records of patients treated over a period of 30 years (1986-2016). Over a 30-year period, 37 malignant neoplasms in the mouth were diagnosed in 4 different centers in Brazil. The average age of patients at the time of diagnosis was 12.2 years, with females and white people being the most affected. Overall, sarcomas were the most common (37.9%), followed by lymphomas (27%). The mandible was the most affected region (37.8%), followed by the maxilla (32.4%), totaling more than 70% of cases (AU)

Carcinoma oral de células escamosas en el paladar: reporte de un caso / Oral squamous cell carcinoma of the palate: a case report

El cáncer oral representa un grave problema de salud a nivel mundial debido a su importante morbilidad y mortalidad. Ocupa la sexta causa de muerte por cáncer y tienen una supervivencia mundial a cinco años cercana a 50%, en gran parte debido a la falta de su reconocimiento en estadios iniciales por parte de los pacientes y de los mismos profesionales de la salud, lo que ocasiona un grave retraso en su diagnóstico y tratamiento. Se presenta el caso de una mujer de 64 años de edad con úlceras de larga evolución en la cavidad oral y quien acude a múltiples profesionales de salud sin ser diagnosticada en las fases iniciales de la enfermedad; acude a la Universidad Autónoma de Tlaxcala en donde se diagnostica carcinoma oral de células escamosas en el maxilar. En el presente artículo se hace énfasis en el reconocimiento de signos clínicos y factores precipitantes que puedan generar sospecha de un crecimiento maligno y así concientizar a los profesionales de la salud para promover la prevención (AU)

Oral cancer represents a serious health problem worldwide due to its significant morbidity and mortality, it is the sixth leading cause of cancer death and has a global 5-year survival rate of 50%, largely due to the lack of recognition in early stages by patients and health professionals themselves, which causes a serious delay in diagnosis and treatment. We present the case of a 64-year-old woman with long-standing ulcers in the oral cavity who went to multiple health professionals without being diagnosed in the initial stages of the disease. She went to the Autonomous University of Tlaxcala where oral squamous cell carcinoma (OSCC) in the maxilla was diagnosed. This article emphasizes the recognition of clinical signs and precipitating factors that may generate suspicion of malignant growth and thus raise awareness among health professionals to promote prevention (AU)

Associação entre lesões de hpv e os carcinomas genitais e da cavidade oral: uma revisão narrativa / Association between hpv lesions and genital and oral cavity carcinomas: a narrative review / Asociación entre lesiones por vph y carcinomas genitales y de cavidad oral: una revisión narrativa

Os Papilomavírus Humano (HPVs) são membros da família Papilomaviridae. O vírus destaca-se pelo seu tropismo por células epiteliais, infectando exclusivamente mucosa epitelial e cutânea. O HPV-16 e HPV-18 são subtipos classificados como de alto risco, conhecidos por sua oncogenicidade, fortemente associados aos cânceres anais, genitais e de orofaringe. Lesões por HPV representam um grande grupo de doenças sexualmente transmissíveis. O objetivo do presente estudo consistiu em realizar uma revisão narrativa sobre a associação entre lesões por HPV e carcinomas genitais e da cavidade oral. Realizamos uma busca na base de dados eletrônicos PubMed, Lilacs, Scielo, Medline e Google Scholar, sendo utilizados artigos publicados entre os anos de 2017-2021, ao fim, foram selecionados 36 artigos. Grande parte das infecções por HPV são subclínicas, ou seja, não apresentam sintomatologia importante e tendem a desaparecer espontaneamente. Desta forma, faz-se necessário ter conhecimento a respeito dos aspectos clínicos e comportamentais dessas lesões, possibilitando o diagnóstico precoce, evitando a evolução para estágios mais invasivos, favorecendo um tratamento efetivo e melhor prognóstico.

Human Papillomaviruses (HPVs) are members of the Papilomaviridae family. The virus stands out for its tropism for epithelial cells, exclusively infecting epithelial and cutaneous mucosa. O HPV-16 and HPV-18 are subtypes classified as high risk, known for their oncogenicity, strongly associated with anal, genital and oropharyngeal cancers. HPV lesions represent a large group of sexually transmitted diseases. The objective of this study was to carry out a narrative review on the association between HPV lesions and genital and oral cavity carcinomas. We carried out a search in the electronic databases PubMed, Lilacs, Scielo, Medline and Google Scholar, using articles published between the years of 2017-2021, at the end, foram selected 36 articles. A large part of HPV infections are subclinical, or seem to, do not present significant symptoms and tend to disappear spontaneously. In this way, it is necessary to be aware of the two clinical and behavioral aspects of these injuries, enabling early diagnosis, avoiding evolution to more invasive stages, favoring effective treatment and better prognosis.

Los virus del papiloma humano (VPH) son miembros de la familia Papillomaviridae. El virus destaca por su tropismo por las células epiteliales, infectando exclusivamente mucosas epiteliales y cutáneas. El VPH-16 y el VPH-18 son subtipos clasificados como de alto riesgo, conocidos por su oncogenicidad, fuertemente asociados con cánceres anales, genitales y orofaríngeos. Las lesiones por VPH representan un gran grupo de enfermedades de transmisión sexual. El objetivo del presente estudio fue realizar una revisión narrativa sobre la asociación entre las lesiones por VPH y los carcinomas genitales y de cavidad oral. Realizamos una búsqueda en la base de datos electrónica PubMed, Lilacs, Scielo, Medline y Google Scholar, utilizando artículos publicados entre los años 2017-2021, al final se seleccionaron 36 artículos. La mayoría de las infecciones por VPH son subclínicas, es decir, no presentan síntomas importantes y tienden a desaparecer espontáneamente. Por lo tanto, es necesario tener conocimiento sobre los aspectos clínicos y conductuales de estas lesiones, que permitan un diagnóstico precoz, evitando la progresión a estadios más invasivos, favoreciendo un tratamiento eficaz y un mejor pronóstico.

Influência da via hippo em carcinomas de células escamosas de língua oral / Influence of the hippo pathway on oral tongue squamous cell carcinomas

O carcinoma de células escamosas de língua oral (CCELO) apresenta altas taxas de morbidade e mortalidade. Apesar dos progressos alcançados nesta área, os pesquisadores continuam em busca de biomarcadores moleculares que tenham valor preditivo no prognóstico dos pacientes e que possibilitem o desenvolvimento de novas estratégias terapêuticas. Neste contexto, várias pesquisas têm destacado o papel da via Hippo com esta finalidade. Portanto, esta pesquisa teve como objetivo avaliar se as proteínas relacionadas à Via Hippo, LATS2 e YAP1, exercem alguma influência sobre o comportamento biológico dos CCELOs. A amostra foi constituída por 26 casos de CCELO e 8 casos de mucosa oral normal como controle. Para avaliar a morfologia dos CCELOs foram utilizadas as gradações propostas pela OMS (2005) e por Almangush et al. (2014). O perfil imunoistoquímico de LATS2 e YAP1 foi avaliado por escores (0-3), com base na sua imunoexpressão em localização intracelular (núcleo e/ou citoplasma) e distribuição epitelial. Para a análise entre os parâmetros estudados foram realizados os testes estatísticos Qui-quadrado de Pearson e Exato de Fisher. A análise de sobrevida foi realizada através do método de Kaplan Meier e do teste log-rank. Para todas as avaliações foram considerados valores significativos com p<0,05. Foi observada alta expressão da LATS2 tanto em mucosa oral normal (100%) quanto na maioria dos CCELOs (73,1%), sem diferença estatística significativa (p=0,160). Foi possível evidenciar o aumento da imunoexpressão da YAP nos casos de CCELO em comparação à mucosa oral normal (p<0,001). Verificou-se ainda que a baixa expressão da LATS2 foi associada com menores taxas de sobrevida livre da doença (p=0,039). Além disso, constatou-se que a elevada expressão da YAP foi associada à classificação de alto risco do modelo BD (p=0,034), sugerindo que a imunoexpressão desta proteína pode estar associada a TEM e invasão celular em CCELO. A elevada expressão de ambas as proteínas, na maioria dos CCELOs, sugere que outras vias de sinalização, além da regulação através da LATS2, podem estar induzindo a expressão nuclear de YAP nestes tumores. Portanto, conclui-se que a via Hippo pode influenciar o comportamento biológico dos CCELOs (AU).

Oral tongue squamous cell carcinoma (OTSCC) has high morbidity and mortality rates. Despite the progress made in this area, researchers continue to search for molecular biomarkers that have predictive value in the prognosis of patients and allow the development of new therapeutic strategies. In this context, several studies have highlighted the role of the Hippo pathway for this purpose. Therefore, this research aimed to evaluate whether the proteins related to the Hippo pathway, LATS2 and YAP1, have some influence on the OTSCC biological behavior. The sample consisted of 26 OTSCC cases and 8 normal oral mucosa cases as control. For the morphological assessment of OTSCC, the gradations proposed by the WHO (2005) and by Almangush et al. (2014) were performed. The immunohistochemical profile of LATS2 and YAP1 was evaluated by scores (0-3), based on their immunoexpression in intracellular location (nucleus and/or cytoplasm) and epithelial distribution. Pearson's Chi-square and Fisher's Exact statistical tests were performed for the analysis of the studied parameters. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. For all evaluations, values with p<0.05 were considered significant. High expression of LATS2 was observed both in normal oral mucosa (100%) and in most OTSCC (73,1%), with no statistically significant difference (p=0,160). It was possible to observe the increase in YAP immunoexpression in cases of OTSCC compared to the normal oral mucosa (p<0.001). It was also found that the LATS2 low expression was associated with lower rates of disease-free survival (p=0.039). Furthermore, YAP high expression was found associated with the BD model's high-risk classification (p=0.034), suggesting this protein immunoexpression may be associated with EMT and cell invasion in OTSCC. The high expression of both proteins in most OTSCC suggests that other signaling pathways, in addition to regulating through LATS2, may be inducing the nuclear YAP expression in these tumors. Therefore, it is concluded that the Hippo pathway can influence the OTSCC biological behavior (AU).

Masseter muscle flap for reconstruction of intra-oral defects in patients with early cancer of posterior-inferior parts of the oral cavity / Retalho do músculo masseter para reconstrução de defeitos intraorais em pacientes com câncer inicial de partes póstero‐inferiores da cavidade oral

Abstract Introduction Early carcinomas of the oral cavity in the posterior-inferior regions poses a challenge for reconstruction due to the lack of muscle support underneath and the limited space available to use some of the frequently-used flaps. Objective This study was done to evaluate the efficacy of the superiorly based masseter muscle flap in reconstruction of intra-oral post- ablation defects in patients with early oral carcinoma of the posterior-inferior part of the oral cavity. Methods A superiorly based masseter muscle flap were used to reconstruct the post-surgical intra- oral defect in 60 patients with early squamous cell carcinoma (T < 4 cm) of the posterior-inferior part of the oral cavity. The patients were followed up at 1-week and 1-month postoperatively to check for flap viability, complications, change in mouth opening and deviation of the mandible on mouth opening. To rule out any recurrence in the oral cavity masseter flaps, the patients were followed up for 1 year. Results The flap was viable in all patients and underwent mucosalization. 7/60 patients had postoperative infections, while 2/60 patients developed an oro-cutaneous fistula which required a secondary corrective procedure. The mean ± standard deviation of change in mouth opening at 1 week postoperatively was +1.917 ± 3.36 mm, which increased to +2.633 ± 2.95 mm at 1 month after surgery. The Friedman test revealed that there was a statistically significant change in mouth opening from preoperative period to the1 week and 1 month postoperative periods (p = 0.000). Female patients showed better improvement in mouth opening postoperatively. The ipsilateral deviation of the mandible on mouth opening was between 0-5 mm in 39 patients, 5-10 mm in 17 patients and more than 10 mm in 4 patients. There were no recurrences noted in the masseter flaps used. Conclusion The study infers that the superiorly based masseter muscle flap is a reliable method for reconstruction in early oral cancer patients yielding good functional results and acceptable cosmesis with nominal postoperative complications.

Resumo Introdução Os carcinomas iniciais da cavidade oral nas regiões póstero‐inferiores representam um desafio para a reconstrução devido à falta de suporte muscular abaixo da região e ao espaço limitado disponível para o uso de alguns dos retalhos mais empregados. Objetivo Avaliar a eficácia do retalho do músculo masseter de base superior na reconstrução de defeitos intraorais pós‐ablação em pacientes com carcinoma oral inicial da parte póstero‐inferior da cavidade oral. Método Um retalho do músculo masseter de base superior foi usado para reconstruir o defeito intraoral pós‐cirúrgico em 60 pacientes com carcinoma espinocelular inicial (T < 4 cm) localizado na parte póstero‐inferior da cavidade oral. Os pacientes foram acompanhados após uma semana e um mês de pós‐operatório para verificação da viabilidade do retalho, complicações, alteração na abertura bucal e desvio da mandíbula na abertura bucal. Para descartar recidiva nos retalhos do masseter, os pacientes foram acompanhados por um ano. Resultados O retalho foi viável em todos os pacientes e foi submetido à mucolização; 7/60 pacientes tiveram infecções pós‐operatórias, enquanto 2/60 pacientes desenvolveram uma fístula orocutânea que exigiu um procedimento corretivo secundário. A média ± desvio‐padrão da alteração na abertura da boca em uma semana de pós‐operatório foi + 1,917 ± 3,36 mm, que aumentou para + 2,633 ± 2,95 mm em um mês de pós‐operatório. O teste de Friedman revelou que houve uma alteração estatisticamente significante na abertura da boca do período pré‐operatório para os períodos de uma semana e um mês de pós‐operatório (p = 0,000). Pacientes do sexo feminino apresentaram maior melhoria na abertura da boca no pós‐operatório. O desvio ipsilateral da mandíbula na abertura da boca ficou entre 0 a 5 mm em 39 pacientes, 5 a 10 mm em 17 pacientes e mais de 10 mm em 4 pacientes. Não foram observadas recidivas nos retalhos de masseter usados. Conclusão O retalho do músculo masseter com base superior é um método confiável para reconstrução em casos de câncer oral inicial, produz bons resultados funcionais e resultados cosméticos aceitáveis com complicações pós‐operatórias insignificantes.

Evaluación de la habilidad diagnóstico precoz del cáncer bucal al estudiante de Estomatología / Evaluation of early oral cancer diagnosis skill in the students of Stomatology / Avaliação das habilidades de diagnóstico precoce do câncer oral de estudantes de Estomatologia

RESUMEN Introducción: En el proceso de enseñanza aprendizaje de los estudiantes de Estomatología se hace necesario constatar el dominio de los conocimientos, acciones, operaciones y actitudes para la prevención del cáncer bucal. Objetivo: Confeccionar un instrumento metodológico que permita la evaluación del desarrollo de la habilidad de diagnóstico precoz del cáncer bucal a los estudiantes de quinto año de Estomatología. Método: Se realizó una investigación educativa, descriptiva con enfoque mixto, en la Universidad de Ciencias Médicas de Guantánamo. El universo lo constituyeron los estudiantes y docentes de quinto año de Estomatología, de ellos se escogió una muestra probabilística de 95 estudiantes y 20 profesores. Para la recogida de la información fueron utilizados métodos del nivel teórico: histórico-lógico, análisis y síntesis, inductivo-deductivo y del nivel empírico: el análisis documental y el criterio de especialistas para validar la propuesta. Resultados: El instrumento mostró un diseño claro y flexible para la evaluación del desarrollo de la habilidad de diagnóstico precoz del cáncer bucal al estudiante de quinto año de Estomatología. Los especialistas en su totalidad consideraron que el mismo es pertinente, útil y factible. Conclusiones: El instrumento permitirá evaluar al estudiante de quinto año de Estomatología la habilidad adquirida para el diagnóstico precoz del cáncer bucal, considerándose un aporte para elevar la calidad del proceso de formación, y garantizar que una vez egresados cumplan con su encargo social según los objetivos del Programa de Detección Precoz del Cáncer Bucal.

ABSTRACT Introduction: In the teaching-learning process for the students of Stomatology, it is necessary to verify the mastery of knowledge, actions, operations and attitudes for the prevention of oral cancer. Objective: Performing a methodological instrument that allows the evaluation of the development of the skill of early diagnosis of oral cancer in fifth year Stomatology students. Method: An educational, descriptive research with a mixed approach was carried out at the University of Medical Sciences in Guantánamo. The universe was constituted by the teachers and students of the fifth year of stomatology, from which a probability sample of 95 students and 20 teachers was chosen. For gathering the information some theoretical methods were used: historical-logical, analysis and synthesis, inductive-deductive, whereas empirical methods were also used: documentary analysis and the criteria of specialists to validate the proposal. Results: This methodological instrument showed a clear and flexible design for the evaluation of the development of the skill of early diagnosis of oral cancer in fifth year Stomatology students. Specialists as a whole considered it to be relevant, useful and feasible. Conclusions: The proposal will allow to evaluate the acquired ability of the fifth year Stomatology students for the early diagnosis of oral cancer, being considered a contribution for increasing the quality of the training process, and to guarantee that once they graduated they fulfill their social task according to the objectives of the Program for the Early Detection of Oral Cancer.

RESUMO Introdução: No processo de ensino-aprendizagem dos estudantes de estomatologia, é necessário verificar o domínio dos conhecimentos, ações, operações e atitudes para a prevenção do câncer oral. Objetivo: Desenvolver um instrumento metodológico para avaliar o desenvolvimento da capacidade de diagnóstico precoce do câncer oral em estudantes de odontologia do quinto ano. Método: Uma pesquisa educacional descritiva com uma abordagem mista foi realizada na Universidade de Ciências Médicas de Guantánamo. O universo foi formado por estudantes e professores no quinto ano de Estomatologia, do qual foi escolhida uma amostra de probabilidade de 95 estudantes e 20 professores. Para a coleta de informações, foram utilizados métodos teóricos: histórico-lógico, análise e síntese, indutivo-dedutivo, e métodos empíricos: análise documental e os critérios de especialistas para validar a proposta. Resultados: O instrumento mostrou um projeto claro e flexível para a avaliação do desenvolvimento da habilidade de diagnóstico precoce do câncer oral em estudantes de odontologia do quinto ano. Os especialistas, como um todo, o consideraram relevante, útil e viável. Conclusões: O instrumento permitirá ao estudante de Estomatologia do quinto ano avaliar as habilidades adquiridas para o diagnóstico precoce do câncer oral, e é considerado uma contribuição para melhorar a qualidade do processo de treinamento e garantir que, uma vez formado, cumpra suas responsabilidades sociais de acordo com os objetivos do Programa de Detecção Precoce do Câncer Oral.

Evaluación del estatus del tejido pulpar postratamiento oncológico / Assessment of the status of the pulp tissue post oncological treatment

La OMS cataloga al cáncer como uno de los principales problemas en el ámbito mundial, los pacientes sometidos a terapia oncológica son más vulnerables a desarrollar complicaciones en los tejidos de la cavidad bucal entre las que tenemos: mucositis, infecciones, osteorradionecrosis. En el manejo endodóntico hay que tomar en consideración que los trata- mientos como yodoterapia, radioterapia y quimioterapia pueden generar efectos sobre el complejo dentinopulpar. El objetivo de este artículo es determinar el estatus del tejido pulpar postratamiento oncológico mediante la revisión sistemática en bases de datos de gran relevancia científica, como PubMed, Scielo, Medigraphic, Science direct. Se concluye que el sistema estomatognático es un receptor importante de estos efectos y secuelas en pacientes con terapia oncológica, el tejido pulpar no está libre de estas secuelas ya que genera daño celular, como la hipovascularidad, hipocelularidad e hipoxia la cual incrementa el riesgo de necrosis de la región (AU)

The WHO lists cancer as one of the main problems worldwide, patients undergoing oncological therapy are more vulnerable to developing complications in the tissues of the oral cavity among which we have: mucositis, infections, osteoradionecrosis. In endodontic management, it should be taken into consideration that treatments such as iodine therapy, radiotherapy, and chemotherapy can generate effects on the dentin-pulp complex. This article aims to determine the status of the pulp tissue after oncologic treatment. Through a systematic review in databases of great scientific relevance, such as PubMed, Scielo, Medigrafhic, Science direct. It is concluded that the stomatognathic system is an important receptor of these effects and sequelae in patients with oncological therapy, the pulp tissue is not free of these sequelae as it generates cellular damage because of the hypo vascularity, hypocellularity, and hypoxia which increases the risk of necrosis of the region (AU)

Oral Mucosal Melanoma: A Case Report and Literature Review

ABSTRACT: Oral mucosal melanoma is an unusual and aggressive malignant tumor that mainly affects the palate of men aged between 50 and 60 years. We present a literature review focusing on the etiopathogenesis and the clinicopathologic features of this entity. In addition, we reported a rare case of an oral mucosal melanoma arising in the left cheek of a 60-yea r- old man. Computed tomography scan revealed infiltration of the tumor to other anatomic structures including the maxillary sinus, the zygomatic bone and the pterygoid processes. Based on its extension, the lesion was considered inoperable and treatment with three-dimensional conformal radiation therapy was proposed but the patient only attended to the first session and died from cancer progression 6 months after the diagnosis. This paper reinforces the importance of inclusion of this malignant tumor in the differential diagnosis of pigmented lesions of the oral mucosa.

RESUMEN: El melanoma de la mucosa oral es un tumor maligno inusual y agresivo que afecta principalmente al paladar de hombres de entre 50 y 60 años. Presentamos una revisión bibliográfica centrada en la etiopatogenia y las características clínico-patológicas de esta entidad. Además, reportamos un caso raro de melanoma de la mucosa oral que surgió en la mejilla izquierda de un hombre de 60 años. La tomografía computarizada reveló la infiltración del tumor a otras estructuras anatómicas, incluido el seno maxilar, el hueso cigomático y los procesos pterigoideos. En base a su extensión, la lesión se consideró inoperable y se propuso tratamiento con radioterapia conformada tridimensional pero el paciente solo asistió a la primera sesión y falleció por progresión del cáncer 6 meses después del diagnóstico. Este trabajo refuerza la importancia de la inclusión de este tumor maligno en el diagnóstico diferencial de las lesiones pigmentadas de la mucosa oral.

Analysis of the efficacy of the pectoralis major myocutaneous flap in reconstructive head and neck surgery.

INTRODUCTION: Although free flaps have been used predominantly in past decades for the soft tissue reconstruction of head and neck malignancies, Pectoralis major myocutaneous flap (PMMF) is still a reliable workhorse for patients with co-existing co-morbidities or low economic status where free flaps are not feasible. PATIENTS AND METHODS: It was a retrospective study done on 36 patients of head and neck malignancies over the period of 5 years in which PMMF was used as a method of reconstruction in our hospital. Patients were followed up for a period of one year and outcome of PMMF was evaluated. RESULTS: Out of 36 patients 31 were of oral cancer and 5 were of carcinoma hypopharynx. Incidence of total flap necrosis was nil and partial flap necrosis was 16.6%. Orocutaneous fistula was found in 16.6%, wound dehiscence was in 19.4% and infection was found in 13.5% of patients. Non-flap related complications were found in 13.8% of patients. 35 out of 36 patients (97.2%) eventually achieved satisfactory surgical outcome of PMMF reconstruction. CONCLUSION: PMMF is a reliable method of reconstruction for head and neck malignancies especially in basic healthcare settings. With minimal expertise and groundwork, it is still a cost-effective workhorse flap for head and neck reconstruction.

Colgajo libre antebraquial radial para reconstrucción microvascular en cáncer de cavidad oral localmente avanzado. Reporte de caso

Introducción: El cáncer de cavidad oral es la malignidad más frecuente dentro de los tumores de cabeza y cuello. El tratamiento estándar curativo corresponde a la cirugía radical cuyo resultado puede impactar de manera significativa la función y morfología del subsitio resecado. La transferencia de colgajos libres mediante técnicas quirúrgicas microvasculares permite expandir la capacidad de resección oncológica de manera segura con adecuada tasa de éxito limitando las secuelas. Caso clínico: Varón de 48 años con cáncer de lengua oral localmente avanzado tratado quirúrgicamente con hemiglosectomía izquierda extendida, disección ganglionar cervical bilateral y reconstrucción microvascularizada con un colgajo libre antebraquial radial. Discusión: Entre un 30% a 35% de las neoplasias de cavidad oral se presentan como enfermedad localmente avanzada. La reconstrucción intraoral suele ser un reto. La planificación quirúrgica del defecto anatómico y funcional son importantes para elegir la opción de reconstrucción y valorar el riesgo de complicaciones posoperatorias. Conclusión: La utilización de colgajos microvasculares libres en la reconstrucción oncológica es fundamental para restaurar el volumen y función de los tejidos afectados por la resección radical. El colgajo libre antebraquial radial es una herramienta versátil debido a sus características físicas y baja tasa de complicaciones en el sitio donante. (provisto por Infomedic International)

Introduction: Oral cavity cancer is the most frequent malignancy within head and neck tumors. The standard curative treatment corresponds to radical surgery whose outcome can significantly impact the function and morphology of the resected subsite. The transfer of free flaps by means of microvascular surgical techniques allows to expand the capacity of oncologic resection in a safe way with an adequate success rate limiting the sequelae. Case report: 48-year-old male with locally advanced oral tongue cancer treated surgically with extended left hemi glossectomy, bilateral cervical lymph node dissection and micro vascularized reconstruction with a radial antebrachial free flap. Discussion: 30% to 35% of oral cavity neoplasms present as locally advanced disease. Intraoral reconstruction is often a challenge. Surgical planning of the anatomic and functional defect are important in choosing the reconstruction option and assessing the risk of postoperative complications. Conclusion: The use of microvascular free flaps in oncologic reconstruction is essential to restore the volume and function of tissues affected by radical resection. The radial antebrachial free flap is a versatile tool due to its physical characteristics and low rate of complications at the donor site. (provided by Infomedic International)

Analysis of the efficacy of the pectoralis major myocutaneous flap in reconstructive head and neck surgery

Introduction: Although free flaps have been used predominantly in past decades for the soft tissue reconstruction of head and neck malignancies, Pectoralis major myocutaneous flap (PMMF) is still a reliable workhorse for patients with co-existing co-morbidities or low economic status where free flaps are not feasible. Patients and methods: It was a retrospective study done on 36 patients of head and neck malignancies over the period of 5 years in which PMMF was used as a method of reconstruction in our hospital. Patients were followed up for a period of one year and outcome of PMMF was evaluated. Results: Out of 36 patients 31 were of oral cancer and 5 were of carcinoma hypopharynx. Incidence of total flap necrosis was nil and partial flap necrosis was 16.6%. Orocutaneous fistula was found in 16.6%, wound dehiscence was in 19.4% and infection was found in 13.5% of patients. Non-flap related complications were found in 13.8% of patients. 35 out of 36 patients (97.2%) eventually achieved satisfactory surgical outcome of PMMF reconstruction. Conclusion: PMMF is a reliable method of reconstruction for head and neck malignancies especially in basic healthcare settings. With minimal expertise and groundwork, it is still a cost-effective workhorse flap for head and neck reconstruction.(AU)

Introducción: Aunque se han utilizado colgajos libres, fundamentalmente en las últimas décadas, para la reconstrucción de tejido blando en tumores malignos de cabeza y cuello, el colgajo miocutáneo de pectoral mayor (PMMF) sigue siendo un método fidedigno para los pacientes con comorbilidades coexistentes o baja situación económica en la que no se tiene acceso a los colgajos libres. Pacientes y métodos: Estudio retrospectivo realizado en 36 pacientes con tumores malignos de cabeza y cuello a lo largo de un periodo de 5 años, en los que se utilizó PMMF como método de reconstrucción en nuestro hospital. Se realizó un seguimiento a los pacientes durante un periodo de un año, evaluándose el resultado de PMMF. Resultados: De los 36 pacientes, 31 tenían cáncer oral y 5 cáncer de hipofaringe. La incidencia de necrosis total del colgajo fue nula, y la de necrosis parcial fue del 16,6%. Se encontró fístula orocutánea en el 16,6% de los casos, dehiscencia de la herida en el 19,4% e infección en el 13,5% de los pacientes. Se encontraron complicaciones no relacionadas con el colgajo en un 13,8% de los pacientes. Treinta y cinco de los 36 pacientes (97,2%) lograron finalmente un resultado quirúrgico satisfactorio de reconstrucción con PMMF. Conclusión: El PMMF es un método de reconstrucción fiable para los tumores malignos de cabeza y cuello, especialmente en los entornos sanitarios básicos. Con experiencia y base preparatoria mínimas sigue siendo un colgajo fiable para la reconstrucción de cabeza y cuello.(AU)

Liquen plano oral: recomendaciones para su diagnóstico y tratamiento / Oral lichen planus: recommendations for diagnosis and treatment

El liquen plano corresponde a una enfermedad crónica de naturaleza inmuno-inflamatoria que puede presentarse en piel y mucosas, siendo la mucosa oral de las zonas más frecuentemente afectadas, incluso como primera única manifestación de la enfermedad. Su etiología no se encuentra totalmente dilucidada, sin embargo, se atribuyen mecanismos autoinmunes como principal causa de la enfermedad. El liquen plano oral (LPO) presenta un amplio espectro de manifestaciones clínicas, pudiendo presentarse como lesiones rojas, blancas o combinaciones de ambas. Sus diversas formas de presentación en la mucosa oral, en conjunto con una histopatología a veces poco específica, determinan que en varios casos su diagnóstico sea complejo para clínicos no familiarizados con la enfermedad. El tratamiento del LPO se enfoca en reducir los síntomas asociados a las lesiones, siendo los corticoides tópicos los fármacos de primera línea. En caso de que el tratamiento con corticoides tópicos no logre controlar la sintomatología, el tratamiento de segunda línea incluye inhibidores de calcineurina o corticoides sistémicos, los que deben ser utilizados con precaución debido a los efectos adversos asociados a estas drogas. La OMS clasifica al LPO como un desorden potencialmente maligno con una tasa de malignización anual estimada en 1.5%-5%, lo que realza la importancia de un correcto diagnóstico y control rutinario, aún en aquellas formas clínicas asintomáticas. Esto último con el fin de poder detectar de manera oportuna cambios clínicos que sugieran su progresión hacia un carcinoma oral de células escamosas.

Lichen planus is a chronic immunological disorder affecting skin and mucous membranes, being the oral cavity one of the more affected areas even as a first or only manifestation of the disease. Its etiology is unclear, but it has been associated with the activation of autoimmune mechanisms. Oral lichen planus (OLP) has a wide spectrum of clinical manifestations including a variety of white lesions, red lesions or a combination of both. In addition, its histopathological features are not always specific. Because of the above, the diagnosis of OLP can be challenging, especially for clinicians who are not entirely familiarized with the disease. OLP treatment is aimed in reducing pain and discomfort, usually with topical steroids. If treatment with topical steroids is unsuccessful, second line treatments include calcineurin inhibitors and systemic steroids. Care has to be taken when using these drugs as they can have considerable adverse side effects. OLP is classified by the WHO as a potentially malignant disorder with a malignant transformation rate estimated between 1.5% and 5%. Thus, its correct diagnosis and proper follow-up are essential even in asymptomatic forms of the disease. This to detect early clinical changes indicative of malignant transformation to an oral squamous cell carcinoma (OSCC).

Reconstrucción mandibular mediante colgajo miocutáneo de pectoral mayor en carcinoma epidermoide, reporte de caso clínico y revisión de la literatura / Mandibular reconstruction using pectoralis major myocutaneous flap in squamous cell carcinoma, clinical case report and literature review

RESUMEN El carcinoma epidermoide surge del epitelio de la mucosa oral, es frecuente en la quinta y sexta décadas de la vida y está típicamente asociado con factores de riesgo como tabaquismo y el consumo de alcohol. En todo el mundo, la incidencia de cáncer oral es más alta en hombres que en mujeres. El incremento en la incidencia del cáncer en México requiere de un manejo adecuado, como colgajos vascularizados para reparar defectos generados por una hemimandibulectomía con márgenes de seguridad. A pesar de la llegada de injertos de tejido libres vascularizados, el colgajo pectoral mayor miocutáneo sigue siendo un colgajo pediculado ampliamente utilizado para la reconstrucción de defectos de tejidos blandos en la región oral y maxilofacial. Se muestra el protocolo quirúrgico realizado en el Hospital Regional "General Ignacio Zaragoza" ISSSTE para el tratamiento de un carcinoma epidermoide mandibular.

ABSTRACT Squamous cell carcinoma arises from the epithelium of the oral mucosa, common in the fifth and sixth decades of life and is typically associated with risk factors such as smoking and alcohol consumption. Worldwide, the incidence of oral cancer is higher among men than women. The increase in the incidence of cancer in Mexico requires proper management and the use of vascularized flaps to repair defects generated by a hemimandibulectomy with safety margins. Despite the advent of vascularized free tissue grafts, the myocutaneous pectoralis major flap remains a pedunculated flap widely used for the reconstruction of soft tissue defects in the oral and maxillofacial region. The surgical protocol carried out at the ISSSTE "General Ignacio Zaragoza" Regional Hospital for the treatment of mandibular squamous cell carcinoma is shown.

Trends of incidence, mortality, and disability-adjusted life years of oral cancer in Latin America / Tendencia de la incidencia, mortalidad y años de vida ajustados por discapacidad del cáncer oral en América Latina

ABSTRACT Objective: To describe the trend in incidence, mortality and Disability Adjusted Life Years of oral cancer in Latin America according to sex between 2000 and 2020. Methods: This ecological study extracted oral cancer information from 20 Latin American countries from the GBD-2020 database. Oral cancer burden was described by age-standardized rate (ASR) of incidence, mortality, and DALYs. The data was compared according to sex and countries. Trends (Average Annual Percentage Change-AAPC) were estimated for each indicator, sex, and country between 2000 and 2020 using Joint-point software. Results: Between 2000 and 2020, the highest incidence of oral cancer (ASR) occurred in Cuba (5.18), Brazil (4.38) and Uruguay (4.62). The countries with the highest mortality for both sexes were (ASR): Cuba (2.89), Brazil (2.71) and the Dominican Republic (2.58). The DALYs registered an average of 37.52 (Women: 22.39; Men: 52.62). The Dominican Republic reports increasing trends in incidence (AAPC: Men: 2.2; Women: 1.4), in mortality (AAPC: Men: 1.8; Women: 1.1), and in DALYs (AAPC: Men: 1.0; Women: 2.0). Costa Rica shows decreasing trends in men in incidence (AAPC: −1.3), mortality (AAPC: −1.6), and DALYs (AAPC: −1.8). Conclusion: Oral cancer shows increasing trends in: the incidence in both sexes in 10 countries, in mortality and DALYs in 6 countries, while the affectation between sexes does not show differences in trends.

RESUMEN Objetivo: Describir la tendencia de la incidencia, mortalidad y los Años de Vida Ajustados por Discapacidad del cáncer oral en América Latina según género entre los años 2000 y 2020. Métodos: Este estudio ecológico extrajo información del cáncer oral de 20 países de América Latina de la base de datos GBD-2020. La carga del cáncer oral se describió según tasa estandarizada por edad (ASR) de incidencia, mortalidad y AVAD. Se estimaron las tendencias (Promedio de cambio porcentual anual — AAPC) en cada indicador, género y país, entre el 2000 y el 2020 usando el software Joint-point. Resultados: Entre 2000 y 2020, la mayor incidencia de cáncer oral (ASR) se presentó en Cuba (5,18), Brasil (4,38) y Uruguay (4,62). Los países con mayor mortalidad para ambos géneros fueron: Cuba (2,89), Brasil (2,71) y República Dominicana (2,58). Los AVAD registraron un promedio de 37,52 (Mujeres: 22,39; Hombres: 52,62). República Dominicana reporta tendencias crecientes en la incidencia (AAPC: Hombres: 2,2; Mujeres: 1,4), en la mortalidad (AAPC: Hombres: 1,8; Mujeres: 1,1), y en los AVAD (AAPC: Hombres: 1,0; Mujeres: 2,0). Costa Rica muestra tendencias decrecientes en los hombres en incidencia (AAPC: −1,3), mortalidad (AAPC: −1,6) y AVAD (AAPC: −1,8). Conclusiones: El cáncer oral muestra tendencias al aumento en: la incidencia en ambos sexos en 10 países, en la mortalidad y los AVAD en 6 países, mientras la afectación entre sexos no muestra diferencias en las tendencias.

Cáncer oral. Factores de riesgo y cambio de tendencia epidemiológica / Oral cancer. Risk factors and change in epidemiological trend

Introducción: El cáncer oral continúa siendo una de las causas de aumento de la morbi-mortalidad en el mundo. Con una incidencia aproximada de 377 mil casos y una mortalidad de 177 mil en el 2020, siendo el carcinoma oral de células escamosas (COCE) el más frecuente. Esta neoplasia afecta predominantemente a hombres y su incidencia aumenta con la edad. Hasta los 80 años, el varón presenta un 40,9% de padecer cáncer y en el caso de las mujeres presentan un 27,0%. A los 85 años, este riesgo aumenta un 49,1% en hombres y un 31,8% en mujeres. Objetivo: Conocer el perfil del paciente con cáncer oral en cuanto a sexo y edad, e identificar los posibles factores etiopatogénicos relacionados con la aparición de ese proceso neoplásico. Material y método: Se realiza un estudio de tipo observacional, descriptivo y retrospectivo en el Servicio de Cirugía Oral y Maxilofacial del Hospital Universitario Ramón y Cajal en el periodo comprendido entre 2004 y 2020. Este estudio ha sido aprobado por el comité de ética de investigación del citado hospital. Resultados: Nuestra muestra ha estado constituida por 46 hombres y 40 mujeres. Todos ellos padecen COCE y tienen una edad media de 66 años ± 14.0 años (66.37; IC al 95%). La mayoría de los pacientes de la muestra han estado concentrados en las décadas de los 60 a los 80 años. Los factores de riesgo más relevantes como predictores de esta enfermedad han sido el tabaco y el alcohol. Los sitios de predilección del carcinoma oral han sido la lengua, la mucosa yugal y el suelo de boca, siendo las localizaciones más frecuentes en el caso de las mujeres la lengua (57,14% vs 42,85%), el reborde alveolar (54,54% vs 45,45%) y la tuberosidad del maxilar (100% vs 0%). (AU)

Introduction: Oral cancer continues to be one of the causes of increased morbidity and mortality in the world. With an approximate incidence of 377 thousand cases and a mortality of 177 thousand in 2020, being oral squamous cell carcinoma (COCE) the most frequent. This neoplasm predominantly affects men and its incidence increases with age. Until the age of 80, men have 40.9% of cancer and in the case of women they have 27.0%. At age 85, this risk increases by 49.1% in men and 31.8% in women. Objective: To know the profi le of the patient with oral cancer in terms of sex and age, and to identify the possible etiopathogenic factors related to the appearance of this neoplastic process. Material and method: An observational, descriptive and retrospective study was carried out in the Oral and Maxillofacial Surgery Service of the Ramón y Cajal University Hospital in the period between 2004 and 2020. This study has been approved by the ethics and research committee of the aforementioned hospital. Results: Our sample consisted of 46 men and 40 women. All of them suffer from COCE and have an average age of 66 years ± 14.0 years (66.37; 95% CI). Most of the patients in the sample have been concentrated in the 60s to 80s. The most relevant risk factors as predictors of this disease have been tobacco and alcohol. The sites of predilection of oral carcinoma have been the tongue, the jugal mucosa and the fl oor of the mouth, being the most frequent locations in the case of women the tongue (57.14% vs 42.85%), the alveolar ridge (54.54% vs 45.45%) and the tuberosity of the maxilla (100% vs 0%). (AU)

Caracterización de pacientes con cáncer oral y su relación con la invasión en profundidad

RESUMEN Fundamento: el cáncer oral supone un reto para cualquier sistema de salud, integrar la invasión en profundidad como factor, a la par del tamaño tumoral, permite un estadiamiento y tratamiento efectivos. Objetivo: caracterizar a pacientes atendidos en el Instituto de Oncología y Radiobiología operados de cavidad oral y corroborar el factor pronóstico de la invasión en profundidad. Método: se realizó un estudio descriptivo, de corte transversal en una serie de casos en el Servicio de Cabeza y Cuello del Instituto de Oncología y Radiobiología, en el período de enero de 2018 a diciembre del 2019. Los datos se obtuvieron en las historias clínicas, se empleó el paquete estadístico SPSS 15.0. Las variables analizadas fueron: edad, sexo, localización y tamaño del tumor, metástasis ganglionar, niveles ganglionares, tratamiento, estado actual, grado de diferenciación, extensión extranodal. Se emplearon los procedimientos de la estadística descriptiva, los resultados se presentan en tablas de frecuencia y relación de variables en números y porcientos. Resultados el rango de edad más frecuente fue entre 51-60 años. El sitio, lengua, fue el más afectado, con grado de diferenciación moderado. Existió relación directa entre metástasis ganglionar oculta y la invasión en profundidad, demostrando una proporcionalidad directa entre mayor profundidad de invasión y la presencia de metástasis ganglionares en la evaluación del patólogo. Conclusiones: las edades superiores a los 50 años y el sexo masculino fueron los más vulnerables a padecer de cáncer oral, la lengua fue el sitio anatómico más afectado. Existió relación directa entre metástasis ganglionar oculta y la invasión en profundidad.

ABSTRACT Background: oral cancer is a challenge for any health system, integrating deep invasion as a factor, along with tumor size, allows effective staging and treatment. Objective: to characterize patients treated at the Institute of Oncology and Radiobiology who underwent oral cavity surgery and to corroborate the prognostic factor of the depth of invasion. Method: a descriptive, cross-sectional study was carried out in a series of cases in the Head and Neck Service of the Oncology and Radiobiology Institute, from January 2018 to December 2019. The data were obtained in the medical records; the statistical package SPSS 15.0 was used. The variables used were: age, sex, location and size of the tumor, lymph node metastasis, lymph node levels, treatment, current status, degree of differentiation, extranodal extension. Descriptive statistics procedures were used; the results are presented in tables of frequency and relation of variables in numbers and percentages. Results: the most frequent age range was between 51-60 years old. The tongue was the most affected site, with a moderate degree of differentiation. There was a direct relationship between hidden lymph node metastasis and invasion in depth, demonstrating a direct proportionality between greater depth of invasion and the presence of lymph node metastases in the pathologist's evaluation. Conclusions: the ages over 50 years old and the male sex were the most vulnerable to suffer from oral cancer, the tongue was the most affected anatomical site. There was a direct relationship between hidden lymph node metastasis and deep invasion.

Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma.

Neoadjuvant PD-1 blockade may be efficacious in some individuals with high-risk, resectable oral cavity head and neck cancer. To explore correlates of response patterns to neoadjuvant nivolumab treatment and post-surgical recurrences, we analyzed longitudinal tumor and blood samples in a cohort of 12 individuals displaying 33% responsiveness. Pretreatment tumor-based detection of FLT4 mutations and PTEN signature enrichment favors response, and high tumor mutational burden improves recurrence-free survival. In contrast, preexisting and/or acquired mutations (in CDKN2A, YAP1, or JAK2) correlate with innate resistance and/or tumor recurrence. Immunologically, tumor response after therapy entails T cell receptor repertoire diversification in peripheral blood and intratumoral expansion of preexisting T cell clones. A high ratio of regulatory T to T helper 17 cells in pretreatment blood predicts low T cell receptor repertoire diversity in pretreatment blood, a low cytolytic T cell signature in pretreatment tumors, and innate resistance. Our study provides a molecular framework to advance neoadjuvant anti-PD-1 therapy for individuals with resectable head and neck cancer.