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Impact of genetic variants in clinical outcome of a cohort of patients with oropharyngeal squamous cell carcinoma.

ABSTRACT: Tobacco- or human papillomavirus- driven oropharyngeal squamous cell carcinomas (OpSCC) represent distinct clinical, biological and epidemiological entities. The aim of this study was to identify genetic variants based on somatic alterations in OpSCC samples from an admixed population, and to test for association with clinical features. The entire coding region of 15 OpSCC driver genes was sequenced by next-generation sequencing in 51 OpSCC FFPE samples. Thirty-five percent of the patients (18/51) were HPV-positive and current or past tobacco consumption was reported in 86.3% (44/51). The mutation profile identified an average of 2.67 variants per sample. Sixty-three percent of patients (32/51; 62.7%) were mutated for at least one of the genes tested and TP53 was the most frequently mutated gene. The presence of mutation in NOTCH1 and PTEN, significantly decreased patient's recurrence-free survival, but only NOTCH1 mutation remained significant after stepwise selection, with a risk of recurrence of 4.5 (HR 95% CI?=?1.11-14.57; Cox Regression p?=?0.034). These results show that Brazilian OpSCC patients exhibit a similar clinical and genetic profile in comparison to other populations. Molecular characterization is a promising tool for the definition of clinical subgroups, aiding in a more precise tailoring of treatment and prognostication.

SUBMITTER: de Carvalho AC

PROVIDER: S-EPMC7305218 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Impact of genetic variants in clinical outcome of a cohort of patients with oropharyngeal squamous cell carcinoma.

de Carvalho Ana Carolina AC Perdomo Sandra S Dos Santos Wellington W Fernandes Gabriela Carvalho GC de Jesus Lais Machado LM Carvalho Raiany Santos RS Scapulatempo-Neto Cristovam C de Almeida Gisele Caravina GC Sorroche Bruna Pereira BP Arantes Lidia Maria Rebolho Batista LMRB Melendez Matias Eliseo ME De Marchi Pedro P Hayes Neil N Reis Rui Manuel RM Carvalho André Lopes AL

Scientific reports 20200619 1

Tobacco- or human papillomavirus- driven oropharyngeal squamous cell carcinomas (OpSCC) represent distinct clinical, biological and epidemiological entities. The aim of this study was to identify genetic variants based on somatic alterations in OpSCC samples from an admixed population, and to test for association with clinical features. The entire coding region of 15 OpSCC driver genes was sequenced by next-generation sequencing in 51 OpSCC FFPE samples. Thirty-five percent of the patients (18/5 ...[more]

PMID: 32561788

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Project description:This study evaluates the prognostic impact of several factors in oropharyngeal squamous cell carcinoma (OPSCC), controlling for human papillomavirus (HPV)-associated tumors and stage (American Joint Committee on Cancer 8th edition). All patients in Southern California Permanente Medical Group diagnosed with OPSCC between 2006 and 2012 tested for p16 immunohistochemistry were included. Review of all pathology materials was combined with central p16 testing. Multivariable analyses were performed. The cohort of 390 patients included 342 p16-positive and 48 p16-negative tumors. For all-comers, on univariate analysis, the following factors, when present, were associated with improved patient survival: p16-positive tumor (n = 324, p < 0.001); crypt versus surface tumor location (n = 312, p = 0.004); nonkeratinizing type (n = 309, p < 0.0001); nonkeratinizing with maturation type (n = 37, p < 0.0001); basaloid pattern (n = 284, p = 0.005); and a broad, pushing border of infiltration (n = 282, p = 0.004). Inferior survival outcomes were observed with: age ≥ 55 years (p < 0.0001); ≥ 10 pack-year smoking history (n = 183, p = 0.003); increasing tumor stage (p < 0.0001); overt radiographic extranodal extension (ORENE) (n = 58, p < 0.0001); low level IV/Vb lymph node involvement (n = 45, p = 0.0002); a jagged pattern of infiltration (n = 76, p = 0.0004); tumor ulceration (n = 76, p = 0.0004); absent lymphocytic infiltrate (p < 0.0001); and concurrent dysplasia (n = 125, p = 0.009). On multivariable analysis, accounting for patient age, smoking history ≥ 10 pack-years, and TNM stage, for patients with p16-positive disease, advanced TNM stage (p = 0.007), the presence of ORENE (p = 0.0002), and low-neck lymphadenopathy (p = 0.0001) were independent negative prognostic factors for disease free survival (DFS). Older age (p < 0.0001), smoking history ≥ 10 pack-years (p = 0.02), advanced TNM stage (p = 0.0002), ORENE (p = 0.004), and low-neck lymphadenopathy (p = 0.002) were independent negative prognostic factors for OS. Among patients with p16-positive OPSCC, older age, smoking history, advanced stage, ORENE, and low-neck lymphadenopathy were significant negative prognostic factors for DFS and/or OS. Further refinement of staging to incorporate additional lymph node findings may be warranted.

Project description:PurposeOur aims are to: (1) estimate prevalence, incidence, clearance and persistence of oral human papillomavirus (HPV) infection among Indigenous Australians; (2) identify risk factors associated with oropharyngeal squamous cell carcinoma (OPSCC)-related HPV types (HPV 16 or 18); (3) develop HPV-related health state valuations and; (4) determine the impact on OPSCC and cervical cancers, and the cost-effectiveness of extending publicly-funded HPV vaccination among Indigenous Australians.ParticipantsParticipants were recruited from February 2018 to January 2019. Twelve-month follow-up occurred from March 2019 to March 2020. Participants provided socio-demographic characteristics, health-related behaviours including tobacco and alcohol use and sexual history. Health state preferences in regard to HPV vaccination, knowledge regarding HPV infection, OPSCC and cervical cancer were collected using a two-stage standard gamble approach. Participants provided saliva samples and DNA for microbial genotyping was extracted.Findings to dateOf the 910 participants who were positive for β-globin at baseline, 35% had any oral HPV infection. The most prevalent HPV types were 13 or 32 (Heck's disease; 23%). The second most prevalent types were associated with OPSCC (HPV 16 or 18; 3.3%). Of the 645 participants who were positive for β-globin at 12-month follow-up, 43% had any HPV infection. Of these, 33% were HPV types 13 or 32 and 2.5% were HPV 16 or 18. Some 588 participants had β-globin positive oral samples at baseline and 12-month follow-up. The prevalence of any oral HPV infection increased from 34% at baseline to 44% at 12-month follow-up; due to increases in HPV types 13 or 32 (20% at baseline and 34% at 12-month follow-up).Future plansFurther funding will be sought to continue follow-up of this cohort, and to include (after a full medical history) a thorough clinical examination of the external head and neck; a complete oral examination and examination of the oropharynx. Blood tests for early stage OPSCC will also be undertaken.

Dataset Information

Impact of genetic variants in clinical outcome of a cohort of patients with oropharyngeal squamous cell carcinoma.

Publications

Impact of genetic variants in clinical outcome of a cohort of patients with oropharyngeal squamous cell carcinoma.

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