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1.
Cancer Med ; 13(3): e7019, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38400665

RESUMO

BACKGROUND: Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC). METHODS: The analyses were conducted by pooling data from three case-control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face-to-face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models. RESULTS: Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC (ORever vs. never = 1.35, 95% CI: 0.96, 1.90). In stratified analysis, while we did not detect associations among never tobacco or alcohol users due to the limited sample size, the association with cocaine use was observed among tobacco users and alcohol drinkers. ORs for ever and high cumulative use (>18 times) versus never use were 1.40 (95% CI: 0.98, 2.00) and 1.66 (95% CI: 1.03, 2.69) among tobacco users, and 1.34 (95% CI: 0.93, 1.92) and 1.59 (95% CI: 1.00, 2.51) among alcohol drinkers, respectively. CONCLUSION: In this pooled analysis, we observed a weak positive association between cocaine inhalation and HNC risk. Our findings provide preliminary evidence of the potential carcinogenic effect of cocaine on HNC. Because of study limitations, including limited number of cocaine users, confounding, and heterogeneity across studies, future investigations will require larger studies with more detailed information on cocaine use history.


Assuntos
Cocaína , Neoplasias de Cabeça e Pescoço , Humanos , Fatores de Risco , Fumar/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/etiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Casos e Controles
2.
Laryngoscope ; 134(1): 222-227, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37345670

RESUMO

OBJECTIVE: To compare functional outcomes of total laryngectomy (TL) with microvascular free tissue transfer (MVFTT) reconstruction in the treatment of dysfunctional larynx (DL) versus salvage therapy for locally recurrent disease in patients with a history of laryngeal squamous cell carcinoma (SCC). METHODS: Retrospective review from a tertiary medical center between August 2015 and August 2022. RESULTS: Sixty-nine patients underwent TL with MVFTT following primary laryngeal radiation or chemoradiation; 15 (22%) patients underwent functional laryngectomy (FL) and 54 (78%) underwent a salvage laryngectomy (SL). There were no total flap failures. Four (6%) patients developed a pharyngocutaneous fistula; one (7%) FL patient and 3 (6%) in the SL cohort. There was no significant difference in average hospital length of stay (LOS) between the cohorts (8.6 ± 3.0 days vs. 12.8 ± 10.1 days, p = 0.12). All patients (100%) in the FL cohort achieved a total oral diet compared to 41 (76%) in the SL cohort (p = 0.03). Two (13%) and 10 (19%) patients developed pharyngoesophageal stenosis in the FL and SL cohorts, respectively (p = 1.0). Nine (60%) and 23 (43%) patients in the FL and SL cohorts underwent tracheoesophageal puncture (TEP) placement, with 89% and 91% achieving fluency, respectively (p = 0.23). CONCLUSION: Although the role of TL for the definitive treatment of laryngeal SCC has decreased over the past 30 years, organ-preservation protocols can impact speech, swallowing, and airway protection with life-threatening consequences. The use of elective FL with MVFTT for the treatment of DL results in similar or better functional outcomes compared to SL for recurrent disease. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:222-227, 2024.


Assuntos
Neoplasias Laríngeas , Laringe , Humanos , Laringectomia/efeitos adversos , Laringectomia/métodos , Resultado do Tratamento , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Estudos Retrospectivos , Laringe/cirurgia , Laringe/patologia , Terapia de Salvação/métodos
3.
J Oral Maxillofac Surg ; 82(3): 347-355, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38103578

RESUMO

BACKGROUND: Patients with solid organ transplant (SOT) are at increased risk of developing aggressive cutaneous malignancies due to their immunosuppression, particularly cutaneous squamous cell carcinoma (cSCC). PURPOSE: There is limited data regarding SOT patients with locally advanced cSCC requiring radical surgery and microvascular free tissue transfer (MVFTT). Our objectives were to characterize outcomes in SOT patients and compare them with a non-SOT cohort. STUDY DESIGN: This is a retrospective cohort study of patients undergoing MVFTT for advanced cSCC of the head and neck between January 2016 and May 2020 at a tertiary referral center. Patients who underwent MVFTT as part of curative intent surgery for advanced cSCC during the study were considered for inclusion. Exclusion criteria included distant metastasis, palliative intent treatment, age less than 18 years, and lip primaries. PREDICTOR: The predictor variable was SOT status. A cohort of non-SOT patients was matched to the SOT cohort based on age, smoking status, tumor stage, and defect size. MAIN OUTCOME VARIABLES: The primary reconstructive outcome was the major surgical complications and secondary outcome measures included major medical complications and minor surgical complications. The primary oncologic outcome was overall survival and the secondary outcome was disease-specific survival. The primary predictor was transplant status. COVARIATES: Covariates included patient comorbidities, prior treatment, tumor stage, type of reconstruction, pathologic findings, and adjuvant therapy. ANALYSIS: Continuous and categorical variables were compared using Student's T test and Fisher's exact test. Survival was calculated using the Kaplan-Meier method and differences in survival between groups were calculated using the log-rank test. Statistical significance was set a priori at P ≤ .05. RESULTS: Fourteen SOT and 14 matched non-SOT patients met inclusion criteria. There was not a statistically significant difference in the rate of major surgical complications (7 vs 7%, P = .74) between the SOT and non-SOT cohorts. Rates of minor (21 vs 43%, P = .26) wound complications and medical complications (0 vs 14%, P = .24) were also similar between the SOT and non-SOT cohorts. Locoregional recurrences and distant metastasis were more common for SOT patients, though this was not statistically significant. Overall survival was significantly worse for SOT patients (21.7 vs 31.0 months, P = .04), though there was not a significant difference in disease-free survival (9.8 vs 31.0 months, P = .17). CONCLUSIONS AND RELEVANCE: MVFTT in the management of SOT patients with locally advanced head and neck cSCC demonstrates similar complication rates with non-SOT patients. While survival and oncologic outcomes are worse in the SOT cohort, aggressive surgical intervention with MVFTT can be performed with comparable complication rates to patients without a history of SOT.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Transplante de Órgãos , Neoplasias Cutâneas , Humanos , Adolescente , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia , Neoplasias de Cabeça e Pescoço/cirurgia
4.
Head Neck ; 45(8): 1943-1951, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37272774

RESUMO

INTRODUCTION: We investigated outcomes and prognostic factors for patients treated for cutaneous angiosarcoma (CA). METHODS: We conducted a retrospective review of patients treated for CA of the face and scalp from 1962 to 2019. All received definitive treatment with surgery, radiation (RT), or a combination (S-XRT). The Kaplan-Meier method was used to estimate outcomes. Multivariable analyses were conducted using the Cox proportional hazards model. RESULTS: For the 143 patients evaluated median follow-up was 33 months. Five-year LC was 51% and worse in patients with tumors >5 cm, multifocal tumors, those treated pre-2000, and with single modality therapy (SMT). These remained associated with worse LC on multivariable analysis. The 5-year disease-specific survival (DSS) for the cohort was 56%. Tumor size >5 cm, non-scalp primary site, treatment pre-2000, and SMT were associated with worse DSS. CONCLUSION: Large or multifocal tumors are negative prognostic factors in patients with head and neck CA. S-XRT improved outcomes.


Assuntos
Neoplasias de Cabeça e Pescoço , Hemangiossarcoma , Neoplasias Cutâneas , Humanos , Hemangiossarcoma/radioterapia , Hemangiossarcoma/cirurgia , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/cirurgia , Estudos Retrospectivos , Modelos de Riscos Proporcionais , Terapia Combinada , Prognóstico , Neoplasias de Cabeça e Pescoço/radioterapia
5.
Oral Oncol ; 142: 106401, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37178654

RESUMO

OBJECTIVES: To characterize the oral microbiota among middle-aged men and identify differences between men with a prevalent oral high-risk (oncogenic) HPV infection and those without. MATERIALS AND METHODS: This was a case-control study nested within a prospective screening study for HPV-related cancers among middle-aged men. 16S rRNA sequencing was used to characterize the oral microbiota and the cobas HPV Test was used to detect presence of oral high-risk HPV types. We determined the overall composition of the oral microbiota and assessed differences in relative abundance of bacterial taxa as well as alpha and beta diversity among men with a prevalent oral high-risk HPV infection compared to men who were HPV-negative. RESULTS: Among 13 high-risk HPV-positive and 30 HPV-negative men, we found significant differences in beta diversity but not alpha diversity. Fretibacterium, F0058, Kingella, Treponema, and Prevotella were more abundant among the high-risk HPV-positive men while Neisseria and Lactobacillus were more abundant among the HPV-negative men. CONCLUSION: This study adds to the evidence that the oral microbiota varies according to oral HPV infection status and may be associated with the natural history of oral HPV infection.


Assuntos
Microbiota , Doenças da Boca , Infecções por Papillomavirus , Pessoa de Meia-Idade , Masculino , Humanos , Papillomavirus Humano , Estudos Prospectivos , RNA Ribossômico 16S/genética , Estudos de Casos e Controles , Microbiota/genética , Papillomaviridae/genética
6.
Cancer Prev Res (Phila) ; 16(3): 127-132, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36596658

RESUMO

Novel preventive interventions are needed to address the rising incidence of human papillomavirus (HPV)-mediated oropharyngeal cancer (HPV+ OPC). This pilot study evaluated the feasibility of a stepped, behavioral and biological screening program for oral oncogenic HPV infection, an intermediate HPV+ OPC outcome.This was a cross-sectional, feasibility study. Eligible 45-74 years old adults identified from three clinical research registries were administered a behavioral risk survey (step 1). Participant tobacco use and sexual behavior history were translated into a quantifiable risk of oral oncogenic HPV DNA, according to prior National Health and Nutrition Examination Survey analyses. Females with >2% risk and males with >7% risk were offered biological screening for oral oncogenic HPV DNA (step 2) via an oral rinse and gargle specimen.A total of 292 individuals were contacted, but only 144 (49%) were reached. Among these, 56 individuals (19%) were uninterested and 18 (13%) were ineligible. Seventy individuals began the survey and 66 completed it (step 1), among whom 46 were classified as low-risk. Among the remaining 20 participants classified as high-risk for an oral oncogenic HPV infection, 5% were current smokers and the median participant had performed oral sex on 10 unique partners. During step 2 (biological screening), 45% (9/20) completed testing, all of whom tested negative for oral oncogenic HPV DNA.In this pilot of a stepped, oral oncogenic HPV screening program, enrollment and study completion were suboptimal. These barriers to screening should be characterized and addressed before reevaluating the feasibility of this program. PREVENTION RELEVANCE: Novel preventive interventions are needed to address the rising incidence of HPV+ OPC. In this feasibility study, we characterized barriers to a two-step, behavioral and biological screening program for oral oncogenic HPV infection, an intermediate outcome for HPV+ OPC.


Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Pessoa de Meia-Idade , Masculino , Idoso , Feminino , Humanos , Adulto , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Estudos de Viabilidade , Inquéritos Nutricionais , Estudos Transversais , Projetos Piloto , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/prevenção & controle , DNA , Papillomavirus Humano , Fatores de Risco , Papillomaviridae/genética , Prevalência
7.
Cancer Med ; 12(1): 569-583, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35695117

RESUMO

BACKGROUND: This study investigated the association of hearing loss and tinnitus with overall health-related quality of life (HRQoL) among long-term oropharyngeal cancer (OPC) survivors. METHODS: This study included OPC survivors treated between 2000 and 2013 and surveyed from September 2015 to July 2016. Hearing loss and tinnitus were measured by asking survivors to rate their "difficulty with hearing loss and/or ringing in the ears" from 0 (not present) to 10 (as bad as you can imagine). Hearing loss and tinnitus scores were categorized as follows: 0 for none, 1-4 for mild, and 5-10 for moderate to severe. The primary outcome was the mean score of MD nderson Symptom Inventory Head & Neck module interference component as a HRQoL surrogate dichotomized as follows: 0 to 4 for none to mild and 5 to 10 for moderate to severe interference. RESULTS: Among 880 OPC survivors, 35.6% (314), reported none, 39.3% (347) reported mild, and 25.1% (221) reported moderate to severe hearing loss and tinnitus. On multivariable analysis, mild (OR, 5.83; 95% CI; 1.48-22.88; p = 0.012) and moderate (OR, 30.01; 95% CI; 7.96-113.10; p < 0.001) hearing loss and tinnitus were associated with higher odds of reporting moderate to severe symptom interference scores in comparison to no hearing loss and tinnitus. This association of hearing dysfunction was consistent with all domains of HRQoL. CONCLUSIONS: Our findings provide preliminary evidence to support the need for continued audiological evaluations and surveillance to detect hearing dysfunction, to allow for early management and to alleviate the long-term impact on QoL.


Assuntos
Perda Auditiva , Neoplasias Orofaríngeas , Zumbido , Humanos , Qualidade de Vida , Zumbido/epidemiologia , Zumbido/etiologia , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Sobreviventes , Neoplasias Orofaríngeas/complicações , Neoplasias Orofaríngeas/terapia
8.
Cancer Epidemiol Biomarkers Prev ; 31(12): 2185-2191, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36126275

RESUMO

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women. METHODS: This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA). RESULTS: 324 evaluable women were enrolled. Primary diagnosis was high-grade dysplasia/cancer of the cervix (77%), vagina (9%), and vulva (14%). Anal HR-HPV was detected in 92 patients (28%) and included HPV-16 in 24 (26%), HPV-18 in 6 (7%), and other HR-HPV types in 72 (78%) patients. Anal cytology was abnormal in 70 patients (23%) and included atypical squamous cells of undetermined significance (80%), low-grade squamous intraepithelial lesion (9%), high-grade intraepithelial lesion (HSIL; 1%), and atypical squamous cells-cannot rule out HSIL (10%). Of these patients, 55 (79%) underwent HRA. Anal biopsies were performed in 14 patients: 2 patients had anal intraepithelial neoplasia (AIN) 2/3, 1 patient had AIN 1, and 11 patients had negative biopsies. Both patients with AIN 2/3 had a history of cervical dysplasia. CONCLUSIONS: Our results suggest an elevated risk of anal HR-HPV infection and cytologic abnormalities in women with lower genital tract dysplasia/cancer. IMPACT: These results add to the growing body of evidence suggesting the need for evaluation of screening methods for anal dysplasia/cancer in this patient population to inform evidence-based screening recommendations.


Assuntos
Doenças do Ânus , Neoplasias do Ânus , Carcinoma in Situ , Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas , Neoplasias do Colo do Útero , Neoplasias Vulvares , Humanos , Feminino , Estudos Transversais , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/diagnóstico , Prevalência , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Ânus/diagnóstico , Doenças do Ânus/epidemiologia , Neoplasias Vulvares/epidemiologia , Carcinoma in Situ/epidemiologia , Vagina/patologia
9.
Cancer ; 128(18): 3383-3391, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35792683

RESUMO

BACKGROUND: Systemic treatments for angiosarcoma remains an area of unmet clinical need. The authors conducted this retrospective study to assess the clinical activity of checkpoint inhibitors in patients with angiosarcoma. The primary objective was to assess the objective response rate, and the secondary objective was to assess the progression-free and overall survival durations and disease control rate. METHODS: Patient data were obtained using The University of Texas MD Anderson Cancer Center Tumor Registry database. The final study population was refined to only include patients who had undergone pembrolizumab monotherapy. The objective response rate was evaluated using RECIST/irRECIST version 1.1. Progression-free survival and overall survival were defined as the time from the initiation of immunotherapy to disease progression or recurrence, death, or last follow-up and to death or last follow-up, respectively. RESULTS: The final cohort comprised 25 patients. Most patients had metastatic disease (72%) and had undergone at least two lines of systemic therapy (80%) before starting pembrolizumab. The objective response rate was 18%, whereas the disease control rate was 59%. The median progression-free survival duration was 6.2 months and was not significantly different between the cutaneous (4.7 months) and visceral angiosarcoma (6.2 months) groups (p = .42). The median overall survival duration was 72.6 months. Toxicities were recorded for eight patients, with fatigue, anemia, constipation, and rash being the most common. CONCLUSIONS: Pembrolizumab shows durable clinical activity in angiosarcoma. These findings suggest that checkpoint inhibition as monotherapy or combination therapy is likely to have a high probability of success.© 2022 American Cancer Society. LAY SUMMARY: This is the largest retrospective study to assess the clinical activity of checkpoint inhibitor monotherapy in angiosarcomas. The study includes an adequate number of patients with visceral angiosarcoma that enabled to obtain meaningful clinical insights that were previously unavailable. Our findings indicate an improvement in progression-free survival with pembrolizumab that is comparable to other active agents in angiosarcoma. Pembrolizumab monotherapy in angiosarcomas also has a favorable tolerability profile. Our findings emphasize the need for prospective studies to evaluate the activity of pembrolizumab monotherapy and combination therapy.


Assuntos
Hemangiossarcoma , Humanos , Imunoterapia , Intervalo Livre de Progressão , Estudos Prospectivos , Estudos Retrospectivos
10.
J Neurol Surg B Skull Base ; 83(4): 359-366, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35903650

RESUMO

Introduction Standardized reconstruction protocols for large open anterior skull base defects with dural resection are not well described. Here we report the outcomes and technique of a multilayered reconstructive algorithm utilizing local tissue, dural graft matrix, and microvascular free tissue transfer (MVFTT) for reconstruction of these deformities. Design This study is a retrospective review. Results Eleven patients (82% males) met inclusion criteria, with five (45%) having concurrent orbital exenteration and eight (73%) requiring maxillectomy. All patients required dural resection with or without intracranial tumor resection, with the average dural defect being 36.0 ± 25.9 cm 2 . Dural graft matrices and pericranial flaps were used for primary reconstruction of the dural defects, which were then reinforced with free fascia or muscle overlay by means of MVFTT. Eight (73%) patients underwent anterolateral thigh MVFTT, with the radial forearm, fibula, and vastus lateralis comprising the remainder. Average total surgical time of tumor resection and reconstruction was 14.9 ± 3.8 hours, with median length of hospitalization being 10 days (IQR: 9.5, 14). Continuous cerebrospinal fluid drainage through a lumber drain was utilized in 10 (91%) patients perioperatively, with an average length of indwelling drain of 5 days. Postoperative complications occurred in two (18%) patients who developed asymptomatic pneumocephalus that resolved with high-flow oxygen therapy. Conclusion A standardized multilayered closure technique of dural graft matrix, pericranial flap, and MVFTT overlay in the reconstruction of large open anterior craniofacial dural defects can assist the reconstructive team in approaching these complex deformities and may help prevent postoperative complications.

11.
Expert Rev Anticancer Ther ; 22(7): 751-761, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35679626

RESUMO

INTRODUCTION: Oropharyngeal cancer (OPC) will be among the most common cancers in men by 2045 due to a rapid rise in human papillomavirus (HPV)-related OPC. Those who survive their cancer often suffer life-long treatment effects and early death. HPV vaccination could prevent virtually all HPV-related cancers but is not an effective preventive strategy for those already exposed. Without a dramatic increase in vaccine uptake in the U.S., HPV vaccination will have a negligible effect on OPC incidence through 2045 and no substantial impact until 2060. Additionally, targeted screening for earlier diagnosis may soon be feasible for those inadequately protected by vaccination. AREAS COVERED: PubMed search for English-language articles related to incidence, screening, and prevention of HPV-related malignancies, focused on OPC in the U.S. EXPERT OPINION: HPV-related OPC incidence will continue to increase for the foreseeable future with prophylactic vaccination offering no substantial public health impact for decades. Consequently, we must rapidly increase vaccination rates and develop screening methods to identify high-risk individuals. Such individuals would be eligible for potential preventive treatments and screening to diagnose early-stage HPV-related OPC allowing less morbid treatments. These methods will bridge the population into an era of decreasing incidence after vaccination takes effect.


Assuntos
Alphapapillomavirus , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Masculino , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/prevenção & controle , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle
12.
Sci Rep ; 12(1): 6662, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459784

RESUMO

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions (2p13.3, rs6546481, Minor Allele (MA) = A, ANTXR1, P = 4.3 × 10-7; 5p13.2-p13.1, rs16903936, MA = G, EGFLAM, P = 5.1 × 10-6; 4q21.1, rs10518156, MA = G, SHROOM3, P = 7.1 × 10-6; 19q13.42, rs11882068, MA = G, NLRP9, P = 1.7 × 10-5; 12q24.33, rs4760542, MA = G, GLT1D1, P = 1.8 × 10-5; and 3q27.3, rs11714564, MA = G, RTP1, P = 2.9 × 10-5. Seven SNPs were associated with lower risk of moderate to severe xerostomia, of which only one mapped to specific genomic region (15q21.3, rs4776140, MA = G, LOC105370826, a ncRNA class RNA gene, P = 1.5 × 10-5). Although our small exploratory study did not reach genome-wide statistical significance, our study provides, for the first time, preliminary evidence of genetic susceptibility to xerostomia. Further studies are needed to elucidate the role of genetic susceptibility to xerostomia.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Xerostomia , Sobreviventes de Câncer , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/genética , Humanos , Proteínas dos Microfilamentos , Neoplasias Orofaríngeas/genética , Medidas de Resultados Relatados pelo Paciente , Receptores de Superfície Celular , Xerostomia/genética
13.
Int J Cancer ; 151(4): 553-564, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35404482

RESUMO

Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines (TSNA) metabolism-related genes play an important role in the development of cancers. We assessed the associations of genetic variants in genes involved in the metabolism of PAHs and TSNA with risk of squamous cell carcinoma of the head and neck (SCCHN) in European populations using two published genome-wide association study datasets. In the single-locus analysis, we identified two SNPs (rs145533669 and rs35246205) in CYP2B6 to be associated with risk of SCCHN (P = 1.57 × 10-4 and .004, respectively), two SNPs (EPHX1 rs117522494 and CYP2B6 rs145533669) to be associated with risk of oropharyngeal cancer (P = .001 and .004, respectively), and one SNP (rs4359199 in HSD17B12) to be associated with risk of oral cancer (P = .006). A significant interaction effect was found between rs4359199 and drinking status on risks of SCCHN and oropharyngeal cancer (P < .05). eQTL and sQTL analyzes revealed that two SNPs (CYP2B6 rs35246205 and HSD17B12 rs4359199) were correlated with alternative splicing or mRNA expression levels of the corresponding genes in liver cells (P < .05 for both). In silico functional annotation suggested that these two SNPs may regulate mRNA expression by affecting the binding of transcription factors. Results from phenome-wide association studies presented significant associations between these genes and risks of other cancers, smoking behavior and alcohol dependence (P < .05). Thus, our study provided some insight into the underlying genetic mechanism of head and neck cancer, which warrants future functional validation.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , 17-Hidroxiesteroide Desidrogenases , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Citocromo P-450 CYP2B6/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Neoplasias de Cabeça e Pescoço/genética , Humanos , Neoplasias Orofaríngeas/genética , Polimorfismo de Nucleotídeo Único , RNA Mensageiro , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
14.
Head Neck ; 44(7): 1520-1527, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35437907

RESUMO

BACKGROUND: Patients on chronic pharmacologic immunosuppressive therapy are at increased risk of wound infection and complications after surgery. There is a paucity of data examining perioperative complications after microvascular free tissue transfer (MVFTT) reconstruction of the head and neck in this patient population. METHODS: Retrospective cohort study performed at two tertiary referral centers between August 2016 and May 2020. RESULTS: Nine hundred and seventy-nine patients underwent MVFTT during the study period; of these 47 (5%) patients were taking chronic immunosuppressive medications. The most common indications for immunosuppression were solid organ transplant and autoimmune disease. Fourteen (30%) patients had surgical complications within 30 days of surgery: 8 (17%) wound dehiscences, 6 (12%) hematomas, and 2 (4%) surgical site infections. There was one total and one partial flap failure with a 30-day reoperation rate of 4%. CONCLUSIONS: MVFTT of the head and neck appears to be safe in patients on chronic pharmacologic immunosuppression.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Terapia de Imunossupressão/efeitos adversos , Pescoço/cirurgia , Complicações Pós-Operatórias/epidemiologia , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos
15.
Mod Pathol ; 35(8): 1045-1054, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35184149

RESUMO

Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells (MuNI) and targeted transcriptomics. P16 was a dominant determinant of LRC, DFS and OS, but tobacco exposure, OP-TIL and MuNI risk features correlated with clinical outcomes independent of p16 status and the combination of p16, OP-TIL and MuNI generated a better stratification of OPSCC risk compared to individual parameters. Differential gene expression (DEG) analysis demonstrated overlap between MuNI and OP-TIL and identified genes involved in DNA repair, oxidative stress response and tumor immunity as the most prominent correlates with survival. Alteration of inflammatory/immune pathways correlated strongly with all risk features and oncologic outcomes. This suggests that development of OPSCC consists of an intersection between multiple required and permissive oncogenic and immunologic events which may be mechanistically linked. The strong relationship between tumor immunity and oncologic outcomes in OPSCC regardless of HPV status may provide opportunities for further biomarker development and precision oncology approaches incorporating immune checkpoint inhibitors for maximal anti-tumor efficacy.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Inibidor p16 de Quinase Dependente de Ciclina/análise , Humanos , Neoplasias Orofaríngeas/patologia , Papillomaviridae , Infecções por Papillomavirus/patologia , Medicina de Precisão , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço
16.
Cancer Cytopathol ; 130(7): 523-530, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35192231

RESUMO

BACKGROUND: This study evaluated the detection accuracy of the Cobas human papillomavirus (HPV) assay for high-risk human papillomavirus (hrHPV) and HPV-16 in head and neck fine-needle aspiration (FNA) specimens with squamous cell carcinoma. METHODS: Head and neck FNA biopsy specimens from 2012 to 2020 were retrospectively collected. Cobas HPV testing was performed on 90 FNA specimens with valid Cervista HPV testing results. Results of Cobas HPV and Cervista HPV assays were compared. A Linear Array or SPF10-LiPA25 HPV genotyping assay resolved cases with discrepant results. The κ value and accuracy of Cobas HPV testing were calculated. The accuracy of the Cobas HPV assay was also determined in 42 FNA needle-rinse specimens. RESULTS: Cobas HPV was positive in 82% of the FNA specimens (74 of 90). The concordance between Cobas HPV and Cervista HPV test results was 88.9% (80 of 90) with substantial agreement (κ = 0.669; 95% CI, 0.481-0.856). With HPV genotyping confirmation in cases with discrepant results between the 2 HPV assays, Cobas HPV showed 100% sensitivity and specificity for hrHPV. HPV-16 was detected in 88% of HPV-positive cases (65 of 74). HPV genotyping confirmed 1 false-negative HPV-16 result and 1 false-positive HPV-16 result. Overall, the accuracy of Cobas HPV for HPV-16 was 97.8%. The accuracy of Cobas HPV in FNA needle-rinse specimens was 100%. CONCLUSIONS: The Cobas HPV assay is highly accurate for determining the HPV status in head and neck FNA specimens. FNA needle rinse is valid for Cobas HPV testing in patients with squamous cell carcinoma.


Assuntos
Alphapapillomavirus , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Biópsia por Agulha Fina/métodos , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Papillomavirus Humano 16 , Humanos , Papillomaviridae/genética , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
17.
Head Neck ; 44(4): 952-963, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35084077

RESUMO

BACKGROUND: The study objective is to identify risk factors associated with fatigue among long-term OPC survivors. METHODS: This cross-sectional study included disease-free OPC survivors treated curatively between 2000 and 2013 who were surveyed from September 2015 to July 2016. The outcome variable was patient-reported fatigue. Multivariable logistic regression was used to identify factors associated with moderate to severe fatigue. RESULTS: Among 863 OPC survivors, 17.4% reported moderate to severe fatigue. Self-reported thyroid problems (OR: 2.01; p = 0.003), current cigarette smoking at time of survey (OR: 3.85; p = 0.001), late lower cranial neuropathy (OR: 3.44; p = 0.002), and female sex (OR: 1.91; p = 0.010) were concurrent risk factors of reporting moderate to severe fatigue. Ipsilateral intensity-modulated radiotherapy (OR: 0.18; p = 0.014) was associated with lower risk of reporting moderate to severe fatigue. CONCLUSIONS: Our study identified thyroid problems, smoking, and late lower cranial neuropathy as associated with moderate to severe fatigue. These findings should be further validated in prospective studies to address fatigue among OPC survivors.


Assuntos
Carcinoma , Neoplasias Orofaríngeas , Estudos Transversais , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Humanos , Neoplasias Orofaríngeas/radioterapia , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Fatores de Risco , Sobreviventes
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