Current Therapeutic Strategies in Patients with Oropharyngeal Squamous Cell Carcinoma: Impact of the Tumor HPV Status.
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ABSTRACT:
SUBMITTER: Bozec A
PROVIDER: S-EPMC8582410 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Head and neck squamous cell carcinoma (HNSCC) is the 9th most common malignant tumor in the world. Based on the etiology, HNSCC has two main subtypes: human papillomavirus (HPV) -related and HPV-unrelated. HPV-positive HNSCC is more sensitive to treatment with favorable survival. Due to the different biological behaviors, individual therapy is necessary and urgently required to deduce the therapeutic intensity of HPV-positive disease and look for a more effective and toxicity-acceptable regimen for HPV-negative disease. EGFR amplification and PI3K/AKT/mTOR pathway aberrant activation are quite common in HPV-positive HNSCC. Besides, HPV infection alters immune cell infiltrating in HNSCC and encompasses a diverse and heterogeneous landscape with more immune infiltration. On the other hand, the chance of HPV-negative cancers harboring mutation on the P53 gene is significantly higher than that of HPV-positive disease. This review focuses on the updated preclinical and clinical data of HPV-positive and HPV-negative HNSCC and discusses the therapeutic strategies of different HPV status in HNSCC.
| S-EPMC8040311 | biostudies-literature
Project description:BackgroundOverall survival for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) has differed by sex, but little is known regarding cancer-specific outcomes. We assessed the independent association of sex with cancer-specific survival in patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).MethodsWe identified 14,183 patients from the Surveillance, Epidemiology, and End Results (SEER) program with OPSCC and tumor HPV status. We used Kaplan-Meier methods to compare overall survival (OS) and OPSCC-specific survival (HNCSS) by patient sex and by tumor HPV status. We then separately fit multivariable survival and competing risk models evaluating the association of sex on these outcomes by tumor HPV status and stratified by the use of guideline-concordant OPSCC treatment.ResultsA total of 10,210 persons with HPV-positive tumors (72.0%) and 3,973 with HPV-negative tumors (28.0%) were identified. A larger proportion of women had HPV-negative tumors (24.0%) versus HPV-positive tumors (13.2%; p < 0.001). Women with HPV-positive tumors were less likely to receive guideline-concordant treatment compared to men. In unadjusted survival analyses, women did not differ in OS or HNCSS compared to men for HPV-positive tumors but had worse OS and HNCSS for HPV-negative tumors. After adjustment, men and women with HPV-positive OPSCC did not differ in OS or HNCSS. However, women with HPV-negative tumors faced worse overall survival (hazard ratio (HR) 1.15, 95% CI 1.02-1.29) that persisted even after stratifying for stage-appropriate treatment (HR 1.28, 95% CI 1.11-1.47).ConclusionsWomen with HPV-positive OPSCC had similar survival outcomes compared to men, but those with HPV-negative tumors have worse overall and cancer-specific survival.
| S-EPMC9085342 | biostudies-literature
Project description:Human papillomavirus induced (HPV+) cancer incidence is rapidly rising, comprising 60-80% of oropharyngeal squamous cell carcinomas (OPSCCs); while rare, recurrent/metastatic disease accounts for nearly all related deaths. An in vivo pre-clinical model for these invasive cancers is necessary for testing new therapies. We characterize an immune competent recurrent/metastatic HPV+ murine model of OPSSC which consists of four lung metastatic (MLM) cell lines isolated from an animal with HPV+ OPSCC that failed cisplatin/radiation treatment. These individual metastatic clonal cell lines were tested to verify their origin (parental transgene expression and define their physiological properties: proliferation, metastatic potential, heterogeneity and sensitivity/resistance to cisplatin and radiation. All MLMs retain expression of parental HPV16 E6 and E7 and degrade P53 yet are heterogeneous from one another and from the parental cell line as defined by Illumina expression microarray. Consistent with this, reverse phase protein array defines differences in protein expression/activation between MLMs as well as the parental line. While in vitro growth rates of MLMs are slower than the parental line, in vivo growth of MLM clones is greatly enhanced. Moreover, in vivo resistance to standard therapies is dramatically increased in 3 of the 4 MLMs. Lymphatic and/or lung metastasis occurs 100% of the time in one MLM line. This recurrent/metastatic model of HPV+ OPSCC retains the characteristics evident in refractory human disease (heterogeneity, resistance to therapy, metastasis in lymph nodes/lungs) thus serving as an ideal translational system to test novel therapeutics. Moreover, this system may provide insights into the molecular mechanisms of metastasis.
| S-EPMC5029694 | biostudies-literature
Project description:We studied the role of tumor-associated trypsin inhibitor (TATI) in serum and in tumor tissues among human papillomavirus (HPV)-positive and HPV-negative OPSCC patients. The study cohort included 90 OPSCC patients treated at the Helsinki University Hospital (HUS), Helsinki, Finland, in 2012-2016. TATI serum concentrations (S-TATIs) were determined by an immunofluorometric assay. Immunostaining was used to assess tissue expression. HPV status was determined with a combination of p16 immunohistochemistry and HPV DNA PCR genotyping. The survival endpoints were overall survival (OS) and disease-specific survival (DSS). A significant correlation was found between S-TATI positivity and poor OS (p < 0.001) and DSS (p = 0.04) in all patients. In HPV-negative cases, S-TATI positivity was linked to poor OS (p = 0.01) and DSS (p = 0.05). In HPV-positive disease, S-TATI positivity correlated with poor DSS (p = 0.01). S-TATI positivity was strongly associated with HPV negativity. TATI serum was negatively linked to a lower cancer stage. TATI expression in peritumoral lymphocytes was associated with favorable OS (p < 0.025) and HPV positivity. TATI expression in tumor and in peritumoral lymphocytes correlated with lower cancer stages. Our results suggest that S-TATI positivity may be a biomarker of poor prognosis in both HPV-positive and HPV-negative OPSCC.
| S-EPMC8200219 | biostudies-literature
Project description:HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a) and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a) overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.
| S-EPMC3794938 | biostudies-literature
Project description:While a variety of human papillomavirus (HPV) tests and surrogate markers are available, currently there is no consensus on the best detection method(s) that should be used to identify HPV-related oropharyngeal squamous cell carcinomas and serve as a standard test (or tests) for routine diagnostic use. As we begin to consider using the results of HPV testing for clinical purposes beyond simple prognostication, such as making decisions on treatment dose or duration or for targeted therapies that may be highly dependent on viral-mediated pathways, we need to be more rigorous in assessing and ensuring the performance of the test (or tests) used. Here we provide an overview of the platforms and technologies, including the strengths and limitations of each test, and discuss what steps are needed to generate confidence in their performance for use in clinical practice.
| S-EPMC6174616 | biostudies-literature
Project description:The global rise of HPV(+) oropharyngeal squamous cell carcinoma (OPSCC) has generated considerable interest underlying its etiology and management. Despite an overall decline in head and neck malignancies, the incidence in OPSCC has by contrast sharply risen, with HPV(+) subtypes now comprising 80% of all OPSCC.1,2 Relative to HPV(-) OPSCC, HPV(+) patients are more responsive to chemoradiation and harbor a 52% risk-of-death reduction.3 Despite this distinct outcome, treatment regimens remain the same for all OPSCC subtypes (smoking-driven and virus-driven), rather than an adaptive approach to what most consider distinct diseases. The short-term effects (e.g., mucositis, odynophagia) and long-term toxicities (e.g., xerostomia, dysphagia, ototoxicity) from treatment substantially affect quality of life, and rival the impact of the cancer itself. Recently published as well as ongoing trials are actively examining deintensification approaches2,4-9, with the goal of diminishing treatment sequelae for HPV(+) subtypes. While deintensification may decrease chemoradiation-related toxicities, it nonetheless may also undertreat a meaningful percentage of HPV(+) patients who may then recur. In examining national trials, 19% of HPV(+) patients had disease progression after therapy, with a two-year survival rate of 60%.10 Current methods to ascertain HPV status involve p16 staining. However, on comparison with gold standard E6/E7 expression by qPCR, p16 harbored a 15% false positivity rate11, suggesting limited utility as a sole biomarker for deintensification. Improved molecular stratification would greatly enhance the clinician’s ability to precisely tailor treatment while minimizing the risk of jeopardizing outcomes. One approach encompasses in-depth proteomic profiling of HPV(+) OPSCC to reveal distinct protein expression profiles and delineate clinically relevant upstream pathways. In turn, these proteomic differences may distinguish higher-risk disease (cases predisposed to recurrence that may benefit from treatment intensification) from lower-risk phenotypes (cases whose treatment response is sufficiently robust to warrant deintensification). Here, two HPV(+) OPSCC cohorts stratified by treatment response are compared via a hybrid data dependent acquisition/data independent acquisition (DDA/DIA) approach via mass spectrometry. We focused on detection of low-abundance proteins to highlight proteomic signatures that can be potentially exploited for treatment stratification.
2022-05-05 | PXD028618 | Pride
Project description:BackgroundHPV-related oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable prognosis, yet patients of color and low socioeconomic status (SES) continue to experience inferior outcomes. We aim to understand how the emergence of HPV has impacted race and SES survival disparities in OPSCC.MethodsA retrospective cohort of 18,362 OPSCC cases from 2010 to 2017 was assembled using the SEER (Surveillance, Epidemiology, and End Results) database. Cox proportional regression and Fine and Gray regression models were used to calculate hazard ratios (HRs) adjusting for race, SES, age, subsite, stage, and treatment.ResultsBlack patients had lower overall survival than patients of other races in HPV-positive and HPV-negative OPSCC (HR 1.31, 95% CI 1.13-1.53 and HR 1.23, 95% CI 1.09-1.39, respectively). Higher SES was associated with improved survival in all patients. Race had a diminished association with survival among high SES patients. Low SES Black patients had considerably worse survival than low SES patients of other races.ConclusionRace and SES interact variably across cohorts. High SES was protective of the negative effects of race, although there remains a disparity in outcomes among Black and non-Black patients, even in high SES populations. The persistence of survival disparities suggests that the HPV epidemic has not improved outcomes equally across all demographic groups.
| S-EPMC10166958 | biostudies-literature
Project description:PurposeIn locally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC), (i) to investigate kinetics of human papillomavirus (HPV) circulating tumor DNA (ctDNA) and association with tumor progression after chemoradiation, and (ii) to compare the predictive value of ctDNA to imaging biomarkers of MRI and FDG-PET.Experimental designSerial blood samples were collected from patients with AJCC8 stage III OPSCC (n = 34) enrolled on a randomized trial: pretreatment; during chemoradiation at weeks 2, 4, and 7; and posttreatment. All patients also had dynamic-contrast-enhanced and diffusion-weighted MRI, as well as FDG-PET scans pre-chemoradiation and week 2 during chemoradiation. ctDNA values were analyzed for prediction of freedom from progression (FFP), and correlations with aggressive tumor subvolumes with low blood volume (TVLBV) and low apparent diffusion coefficient (TVLADC), and metabolic tumor volume (MTV) using Cox proportional hazards model and Spearman rank correlation.ResultsLow pretreatment ctDNA and an early increase in ctDNA at week 2 compared with baseline were significantly associated with superior FFP (P < 0.02 and P < 0.05, respectively). At week 4 or 7, neither ctDNA counts nor clearance were significantly predictive of progression (P = 0.8). Pretreatment ctDNA values were significantly correlated with nodal TVLBV, TVLADC, and MTV pre-chemoradiation (P < 0.03), while the ctDNA values at week 2 were correlated with these imaging metrics in primary tumor. Multivariate analysis showed that ctDNA and the imaging metrics performed comparably to predict FFP.ConclusionsEarly ctDNA kinetics during definitive chemoradiation may predict therapy response in stage III OPSCC.
| S-EPMC8785355 | biostudies-literature
Project description:We investigated the ability of machine-learning classifiers on radiomics from pre-treatment multiparametric magnetic resonance imaging (MRI) to accurately predict human papillomavirus (HPV) status in patients with oropharyngeal squamous cell carcinoma (OPSCC). This retrospective study collected data of 60 patients (48 HPV-positive and 12 HPV-negative) with newly diagnosed histopathologically proved OPSCC, who underwent head and neck MRIs consisting of axial T1WI, T2WI, CE-T1WI, and apparent diffusion coefficient (ADC) maps from diffusion-weighted imaging (DWI). The median age was 59 years (the range being 35 to 85 years), and 83.3% of patients were male. The imaging data were randomised into a training set (32 HPV-positive and 8 HPV-negative OPSCC) and a test set (16 HPV-positive and 4 HPV-negative OPSCC) in each fold. 1618 quantitative features were extracted from manually delineated regions-of-interest of primary tumour and one definite lymph node in each sequence. After feature selection by using the least absolute shrinkage and selection operator (LASSO), three different machine-learning classifiers (logistic regression, random forest, and XG boost) were trained and compared in the setting of various combinations between four sequences. The highest diagnostic accuracies were achieved when using all sequences, and the difference was significant only when the combination did not include the ADC map. Using all sequences, logistic regression and the random forest classifier yielded higher accuracy compared with the that of the XG boost classifier, with mean area under curve (AUC) values of 0.77, 0.76, and 0.71, respectively. The machine-learning classifier of non-invasive and quantitative radiomics signature could guide the classification of the HPV status.
| S-EPMC7568530 | biostudies-literature