HPV-negative Oropharyngeal Cancer Research Articles

Imaging Descriptors of Human Papilloma Virus-mediated and Human Papilloma Virus-negative Oropharyngeal Cancers in Indian Subcontinental Patients

Abstract Background: Nearly 24,000 new cases of oropharyngeal cancers (OPCs) are reported per year in India, constituting 3.9% of cancers in all sites. By 2009, Human papilloma virus (HPV), in particular HPV-16, was established as an etiological factor and even a causative agent in OPCs being associated with up to 70% OPCs. Prior imaging-based studies have described certain differentiating factors between HPV-mediated and HPV-negative OPC, highlighting computed tomography and magnetic resonance characteristics that could help differentiate the two groups. Our study aimed to evaluate any imaging differences between HPV-mediated and non-HPV-mediated oropharyngeal malignancies in the Indian subcontinent population. Methods: Seventy-nine patients from the Indian subcontinent who were referred to a tertiary center in southern India between the period of January 2019 to September 2020 (19 months) were included in the study. Imaging descriptors were documented by blinded radiologists, and univariate and multivariate analysis of various imaging descriptors and imaging differences between HPV-mediated and non-HPV cases were attempted to be identified. Results: We found no statistically significant imaging differences between HPV-mediated and non-HPV-mediated oropharyngeal malignancies. The only epidemiologically significant difference in the two groups was that in women and nonsmokers, HPV-mediated malignancies were more common. Conclusion: HPV-mediated and HPV-negative malignancies have similar primary tumor as well as nodal imaging characteristics. Previously cited differences in the two groups, in Western literature, could not be demonstrated in our population. It implores further research into whether downstaging of treatment and better prognosis of HPV-mediated malignancies is actually applicable in the Indian subcontinent setting.

Predictive potential of dynamic contrast-enhanced MRI and plasma-derived angiogenic factors for response to concurrent chemoradiotherapy in human papillomavirus-negative oropharyngeal cancer.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascularity, which depends on the process of angiogenesis and affects tumour response to treatment. Our study explored the associations between DCE-MRI parameters and the expression of plasma angiogenic factors in human papilloma virus (HPV)-negative oropharyngeal cancer, as well as their predictive value for response to concurrent chemoradiotherapy (cCRT). Twenty-five patients with locally advanced HPV-negative oropharyngeal carcinoma were prospectively enrolled in the study. DCE-MRI and blood plasma sampling were conducted before cCRT, after receiving a radiation dose of 20 Gy, and after the completion of cCRT. Perfusion parameters ktrans, kep, Ve, initial area under the curve (iAUC) and plasma expression levels of angiogenic factors (vascular endothelial growth factor [VEGF], connective tissue growth factor [CTGF], platelet-derived growth factor [PDGF]-AB, angiogenin [ANG], endostatin [END] and thrombospondin-1 [THBS1]) were measured at each time-point. Patients were stratified into responders and non-responders based on clinical evaluation. Differences and correlations between measures were used to generate prognostic models for response prediction. Higher perfusion parameter ktrans and higher plasma VEGF levels successfully discriminated responders from non-responders across all measured time-points, whereas higher iAUC and higher plasma PDGF-AB levels were also discriminative at selected time points. Using early intra-treatment measurements of ktrans and VEGF, a predictive model was created with cut-off values of 0.259 min-1 for ktrans and 62.5 pg/mL for plasma VEGF. Early intra-treatment DCE-MRI parameter ktrans and plasma VEGF levels may be valuable early predictors of response to cCRT in HPV-negative oropharyngeal cancer.

Transoral Robotic Surgery and Human Papillomavirus Infection: Impact on Oropharyngeal Cancer Prognosis.

Background/Objective: The incidence of oropharyngeal cancer (OPC) remains significant, with a rising prevalence of HPV-positive (HPV+) cases, underscoring the growing importance of appropriate treatment approaches for this condition. While HPV+ OPC typically exhibits a more favorable prognosis than HPV-negative (HPV-) OPC, certain HPV+ OPC patients still face adverse outcomes. This study aimed to assess the effectiveness of TORS versus traditional surgery in treating OPC patients and investigate the prognostic implications of specific variants in the HPV genome. Methods: The clinical information, including pathological features, treatments, and outcomes (death), of 135 OPC patients treated with traditional surgery from 2008 to 2018 (the non-TORS group) and 130 OPC patients treated with TORS from 2017 to 2021 (the TORS group) were obtained from Sun Yat-sen University Cancer Center (SYSUCC). A comparative analysis of 3-year overall survival (OS) was performed between these two groups. Furthermore, we conducted next-generation sequencing for the HPV16 genome of the 68 HPV+ OPC cases to characterize single-nucleotide variations (SNVs) in the HPV16 genome and evaluate its association with HPV+ OPC patient survival. Results: The comparative analysis of 3-year OS between the two groups (TORS vs. non-TORS) revealed a significant prognostic improvement in the TORS group for OPC patients with a T1-T2 classification (89.3% vs. 72.0%; p = 1.1 × 10-2), stages I-II (92.1% vs. 82.2%; p = 4.6 × 10-2), and stages III-IV (82.8% vs. 62.2%; p = 5.7 × 10-2) and for HPV- patients (85.5% vs. 33.3%; p < 1.0 × 10-6). Furthermore, three SNVs (SNV1339A>G, SNV1950A>C, and SNV4298A>G) in the HPV16 genome were identified as being associated with worse survival. These SNVs could alter protein interactions and weaken the binding affinity for MHC-II, promoting viral amplification and immune evasion. Conclusions: TORS exhibited a superior prognosis to traditional surgery in OPC patients. Additionally, identifying specific SNVs within the HPV16 genome provided potential prognostic markers for HPV+ OPC. These significant findings hold clinical relevance for treatment decision-making and prognostic assessment in patients with OPC.

Clinical prognostic factors to guide treatment strategy for HPV‑positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real‑world experience.

The role of induction chemotherapy (IC) in locally advanced oropharyngeal cancer (OPC) remains debatable, and suitable candidates for de-escalation treatment in these patients have not been fully identified. Therefore, the present study aimed to identify high-risk candidates for human papillomavirus (HPV)-positive OPC by analyzing patients who underwent IC followed by chemoradiotherapy (CRT) to guide optimal treatment strategies. Patients diagnosed with stage III-IVA OPC and treated with a minimum of two cycles of IC followed by CRT, between 2004 and 2020, were retrospectively reviewed. All the patients were restaged according to the American Joint Committee on Cancer, 8th edition. The overall response rate and survival outcomes associated with clinical factors based on HPV status were analyzed using univariate and multivariate analyses. The present study analyzed 105 patients with a median age of 60 years (range, 40-76 years). Among 105 patients, 40 (38.1%) were HPV-negative and 65 (61.9%) HPV-positive. In all patients, survival outcomes were notably poorer in patients aged ≥60 years (P=0.006) and those who did not achieve complete response post-CRT (P<0.001), irrespective of the HPV status. The median relative dose intensity of IC was ≥80%, indicating adequate treatment, regardless of age. In contrast to patients with HPV-negative OPC, age ≥60 years (P=0.011) and T4 stage (P=0.019) emerged as substantial poor prognostic factors for survival outcomes in patients with HPV-positive OPC. Patients with HPV-positive OPC were categorized into three groups based on the number of clinical factors at diagnosis (such as age and T4 stage). The progression-free and overall survival showed significant stratification across each group as the number of high-risk factors increased despite IC and CRT. The findings indicated that patients with these high-risk factors require a cautious therapeutic strategy even when they are diagnosed with HPV-positive OPC, and the role of combined modality, including IC, will need to be investigated in a randomized trial to be routinely incorporated into clinical practice.

Quantification of human papillomavirus cell-free DNA from low-volume blood plasma samples by digital PCR.

The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA) isolated from 3 to 4 mL blood plasma has been successfully used for therapy surveillance. A highly discussed application of HPV-cfDNA is early detection of HPV-OPC. This requires sensitive and specific cfDNA detection as cfDNA levels can be very low. To study the predictive power of pre-diagnostic HPV-cfDNA, archived samples from epidemiological cohorts with limited plasma volume are an important source. To establish a cfDNA detection workflow for low plasma volumes, we compared cfDNA purification methods [MagNA Pure 96 (MP96) and QIAamp ccfDNA/RNA] and digital PCR systems (Biorad QX200 and QIAGEN QIAcuity One). Final assay validation included 65 low-volume plasma samples from oropharyngeal cancer (OPC) patients with defined HPV status stored for 2-9 years. MP96 yielded a 28% higher cfDNA isolation efficiency in comparison to QIAamp. Both digital PCR systems showed comparable analytical sensitivity (6-17 copies for HPV16 and HPV33), but QIAcuity detected both types in the same assay. In the validation set, the assay had 80% sensitivity (n = 28/35) for HPV16 and HPV33 and a specificity of 97% (n = 29/30). In samples with ≥750 µL plasma, the sensitivity was 85% (n = 17/20), while in samples with <750 µL plasma, it was 73% (n = 11/15). Despite the expected drop in sensitivity with decreased plasma volume, the assay is sensitive and highly specific even in low-volume samples and thus suited for studies exploring HPV-cfDNA as an early HPV-OPC detection marker in low-volume archival material.IMPORTANCEHPV-OPC has a favorable prognosis compared to HPV-negative OPC. However, the majority of tumors is diagnosed after regional spread, thus making intensive treatment necessary. This can cause lasting morbidity with a large impact on quality of life. One potential method to decrease treatment-related morbidity is early detection of the cancer. HPV cfDNA has been successfully used for therapy surveillance and has also been detected in pre-diagnostic samples of HPV-OPC patients. These pre-diagnostic samples are only commonly available from biobanks, which usually only have small volumes of blood plasma available. Hence, we have developed a workflow optimized for small-volume archival samples. With this method, a high sensitivity can be achieved despite sample limitations, making it suitable to conduct further large-scale biobank studies of HPV-cfDNA as a prognostic biomarker for HPV-OPC.

Clinical prognostic factors to guide treatment strategy for HPV-positive oropharyngeal cancer from treatment outcomes of induction chemotherapy: A real-world experience.

e18014 Background: The role of induction chemotherapy (IC) in locally advanced oropharyngeal cancer (OPC) remains a topic of debate and suitable candidates for de-escalation treatment in these patients have not been fully identified. This study aimed to identify high-risk groups for HPV-positive OPC by analyzing patients who underwent IC followed by chemoradiotherapy (CRT) to guide optimal treatment strategies. Methods: Between 2004 and 2020, we reviewed patients with OPC diagnosed with stage III-IVA who underwent a treatment regimen comprising a minimum of two cycles of IC followed by CRT.In this study, all patients were re-staged according to the American Joint Committee on Cancer (AJCC) 8th edition, and we analyzed the overall response rate and survival outcomes associated with clinical factors based on HPV status by utilizing univariate and multivariate analyses. Results: This study analyzed 105 patients with a median age of 60 years (range: 40–76 years). Among 105 patients, 40 (38.1%) were HPV-negative, and 65 (61.9%) were HPV-positive. Through a median follow-up of 60.0 months (range, 5–60 months), no significant differences in progression-free survival (PFS) (p = 0.172) and overall survival (OS) (p = 0.064) were observed based on HPV status, regardless of no differences in relative dose intensity of IC and cumulative dose of radiation and cisplatin in CRT. In all patients, survival outcomes were notably poorer in patients aged ≥ 60 years ( p = 0.006) and those who did not achieve complete response (non-CR) post-CRT ( p &lt; 0.001), irrespective of HPV status. All have received sufficient IC with a median RDI of 80% or more in both age &lt; 60 years and age ≥ 60 years. Unlike HPV-negative OPC, where age and T stage showed no significant correlation, in HPV-positive OPC, age ≥ 60 years ( p = 0.011) and T4 stage ( p = 0.019) emerged as substantial poor prognostic factors for survival outcomes despite IC and CRT. Utilizing these results, we categorized HPV-positive OPC patients into three groups based on the number of clinical risk factors at diagnosis (age, T4 stage), the PFS and OS showed significant stratification across each group as the number of clinical risk factors increased. Conclusions: This study revealed that age and T stage significantly influenced on prognosis in HPV-positive OPC but not in HPV-negative OPC. Considering our result, HPV-positive OPC exhibiting these risk factors requires a careful treatment strategy, and combined treatments, including immunotherapy, may be considered to enhance treatment outcomes for these patients.

EGFR overexpression and macrophage infiltration correlate with poorer prognosis in HPV-negative oropharyngeal cancer via STAT6 signaling.

The prevalence of HPV-negative oropharyngeal cancer (OPC) is higher in Asian countries. Patients with HPV-negative OPC suffer poor outcomes. Multi-omics analysis could provide researchers and clinicians with more treatment targets for this high-risk group. We aimed to explore the prognostic significance of EGFR overexpression and macrophage infiltration in OPC, especially HPV-negative OPC in this study. EGFR alternation was evaluated with TCGA, PanCancer Atlas through cBioProtal. EGFR mRNA expression in HPV-negative head and neck squamous cell carcinoma was analyzed using the Tumor Immune Estimation Resource (TIMER 2.0). We also examined EGFR/STAT6/MRC1 expression in paraffin-embedded tissues from a p16-negative OPC cohort. The correlation between EGFR expression and macrophage activation was explored using Person's correlation coefficient. The impact of biomarkers or macrophage infiltration on 5-year overall survival and recurrence-free survival were analyzed using Kaplan-Meier survival curves. EGFR alteration rate was 15%, 13%, and 0% for HPV-negative HNSCC (excluding OPC), HPV-negative OPC, and HPV-positive OPC. High EGFR expression was associated with increased tumor infiltration of immune cells, such as macrophages. We observed positive correlations between EGFR, STAT6, and MRC1 expression in p16-negative OPC. Higher MRC1 expression was associated with poorer survival rates. There is strong correlation between EGFR overexpression and M2 polarization in patients with p16-negative OPC. Immunotherapy with or without EGFR inhibitor could be considered in these high-risk patients.

Extra-Capsular Spread of Lymph Node Metastasis in Oral, Oropharyngeal and Hypopharyngeal Cancer: A Comparative Subsite Analysis

Background: The extra-capsular spread (ECS) of lymph node metastasis (LNM) is a hallmark of aggressive primary tumor phenotype in head and neck cancer (HNC); however, the factors influencing ECS are poorly understood. Patients and Methods: This was a retrospective study, including 190 cases of oral tongue cancer (OTC), 148 cases of oropharyngeal cancer (OPC) (118 HPV-positive and 30 HPV-negative), and 100 cases of hypopharyngeal cancer (HPC). Tumor dimension, tumor biological variables (lymphovascular/perineural invasion and histologic grade), and LNM variables (LNM number and size) were analyzed according to the presence of ECS using multivariable logistic regression and receiver operating characteristic (ROC) curve analyses. Results: LNM variables were significant factors for ECS in all subsites of HNC (p &lt; 0.05), except HPV-positive OPC. In OTC, tumor dimensional variables were significantly related to ECS (p &lt; 0.01). Meanwhile, in OPC and HPC, neither the primary tumor dimension nor the T status were significant factors for ECS occurrence. The predictability of ECS by ROC curve using multiple variables was 0.819 [95% confidence interval: 0.759–0.878] in OTC, 0.687 [0.559–0.815] in HPV-positive OPC, 0.823 [0.642–1.000] in HPV-negative OPC, and 0.907 [0.841–0.973] in HPC. Conclusion: LNM variables were correlated with ECS occurrence for most HNC subsites, and site-dependent primary tumor characteristics might contribute differentially to the ECS development of LNM in HNC.

A comparison of loco-regional relapse pattern in HPV positive vs negative oropharyngeal cancers following radiotherapy; relation to pretreatment FDG-PET and radiotherapy target volumes

Background Previous studies have shown that a large proportion of relapses in head-and neck squamous cell carcinoma (HNSCC) following radiotherapy (RT) occur in the pretreatment FDG-PET avid volume (GTV-PET). The aim of the current work was to see if this was valid also in an oropharynx squamous cell carcinoma (OPSCC) only population, and to compare the loco-regional relapse pattern between HPV positive and HPV negative patients. Material and methods Among 633 OPSCC patients treated between 2009 and 2017, 46 patients with known HPV (p16) status and isolated loco-regional relapse were included. Oncologists contoured relapse volumes (RV) on relapse scans (PET/CT, CT or MR), which were thereafter deformed to match the anatomy of the planning CTs. The point of origin (center of volume) of the deformed RVs were determined and analyzed in relation to the RT target volumes (GTV-PET, GTV and CTVs). The relapse pattern was compared between HPV positive and HPV negative patients using Fischer’s exact test. Results Sixty RVs were contoured in the 46 patients. 55% (95% CI 44–67%) of relapses originated in GTV-PET, while the other RT volumes harbored 12% (5–20%) (GTV), 18% (9–28%) (high risk CTV) and 5% (0–11%) (low risk CTV) of relapses. Six relapses were found outside the RT target volumes. No significant difference in relapse pattern between HPV positive and HPV negative patients was found (p = .95). Conclusion There were no signs of difference in loco-regional relapse pattern between HPV positive and HPV negative patients. In agreement with previous findings, GTV-PET was the most frequent RT target volume of relapse.

O3.1 Differences between HPV positive and HPV negative oropharyngeal cancer detected by Non-Gaussian IVIM

O3.1 Differences between HPV positive and HPV negative oropharyngeal cancer detected by Non-Gaussian IVIM

Analysis of Outcomes following TORS in a Mixed Cohort of Recurrent and New T1-T2 Oropharyngeal Cancer- A Single Institution Study.

. The transoral robotic surgery is a newer modality being used in surgical treatment of early oropharyngeal cancer. The aim of this study is to assess the outcome of these cases in terms of two year disease free survival and overall survival. Between July 2016 and September 2018, 58 patients suffering from early oropharyngeal cancer underwent transoral robotic surgery with neck dissection at a tertiary referral centre. 43 of them have completed two years follow up and were analyzed for disease free survival and overall survival. 41 patients had HPV analysis done . The surgical margins were positive in 9/43 patients ( 6 in upfront surgery and 3 in the salvage cohort). Adjuvant therapy was administered to 16/34 patients on account of either positive margins or multiple nodal metastasis. 88% patients were found to be HPV negative. The two year disease free survival for the upfront cohort was 88.2% and salvage cohort was 55.5%. The overall survival was 86.05%. The study highlights good locoregional control and two year disease free survival in HPV negative oropharyngeal cancer undergoing robotic surgery. Additionally, a positive surgical margin and recurrence were the statistically significant variables influencing 2 year disease free survival. Trans oral robotic surgery is an excellent tool for early tumors of the oropharynx. The presence of a positive surgical margin is a grim sign for survival and has a significant impact on positive outcome. The online version contains supplementary material available at 10.1007/s12070-022-03139-5.

Current Evidence of a Deintensification Strategy for Patients with HPV-Related Oropharyngeal Cancer.

Simple SummaryHuman papillomavirus (HPV)-related oropharyngeal cancer represents a distinct disease entity, showing favorable treatment responses and survival outcomes. While the deintensification of treatment for HPV-related oropharyngeal cancer is widely considered necessary, details concerning patient selection and optimal strategies are undetermined. The heterogeneity of study populations and interventions in trials complicate the ability of physicians to apply the results in daily practice. The evolving landscape also requires physicians to consistently update the results of these trials. This article reviews the most recent evidence on the deintensification of HPV-related oropharyngeal cancer. We aim to provide physicians with some guidance regarding management options and assist researchers in appropriately designing trials in the future.Human papillomavirus (HPV)-related oropharyngeal cancer differs from HPV-negative oropharyngeal cancer in terms of etiology, epidemiology, and prognosis. Younger and lower comorbidity patient demographics and favorable prognosis allow HPV-related oropharyngeal cancer patients to anticipate longer life expectancy. Reducing long-term toxicities has become an increasingly important issue. Treatment deintensification to reduce toxicities has been investigated in terms of many aspects, and the reduction of radiotherapy (RT) dose in definitive treatment, replacement of platinum-based chemotherapy with cetuximab, response-tailored dose prescription after induction chemotherapy, and reduction of adjuvant RT dose after transoral surgery have been evaluated. We performed a literature review of prospective trials of deintensification for HPV-related oropharyngeal cancer. In phase II trials, reduction of RT dose in definitive treatment showed comparable survival outcomes to historical results. Two phase III randomized trials reported inferior survival outcomes for cetuximab-based chemoradiation compared with cisplatin-based chemoradiation. In a randomized phase III trial investigating adjuvant RT, deintensified RT showed noninferior survival outcomes in patients without extranodal extension but worse survival in patients with extranodal extension. Optimal RT dosage and patient selection require confirmation in future studies. Although many phase II trials have reported promising outcomes, the results of phase III trials are needed to change the standard treatment. Since high-level evidence has not been established, current deintensification should only be performed as part of a clinical study with caution. Implementation in clinical practice should not be undertaken until evidence from phase III randomized trials is available.

The Prognostic Role of Baseline Eosinophils in HPV-Related Cancers: a Multi-institutional Analysis of Anal SCC and OPC Patients Treated with Radical CT-RT

Background and AimAnal squamous cell carcinoma (SCC) and oropharyngeal cancer (OPC) are rare tumors associated with HPV infection. Bioumoral predictors of response to chemoradiation (CT-RT) are lacking in these settings. With the aim to find new biomarkers, we investigated the role of eosinophils in both HPV-positive anal SCC and HPV-related oropharyngeal cancer (OPC).MethodsWe retrieved clinical and laboratory data of patients with HPV-positive anal SCC treated with CT-RT in 5 institutions, and patients with locally advanced OPC SCC treated with CT-RT in 2 institutions. We examined the association between baseline eosinophil count (the best cutoff has been evaluated by ROC curve analysis: 100 × 10^9/L) and disease-free survival (DFS). Unadjusted and adjusted hazard ratios by baseline characteristics were calculated using the Cox proportional hazards model.ResultsThree hundred four patients with HPV-positive anal SCCs and 168 patients with OPCs (122 HPV-positive, 46 HPV-negative diseases) were analyzed. In anal SCC, low eosinophil count (< 100 × 10^9/L) correlates to a better DFS (HR = 0.59; p = 0.0392); likewise, in HPV-positive OPC, low eosinophil count correlates to a better DFS (HR = 0.50; p = 0.0428). In HPV-negative OPC, low eosinophil count confers worse DFS compared to high eosinophil count (HR = 3.53; p = 0.0098). After adjustment for age and sex, eosinophils were confirmed to be independent prognostic factors for DFS (HR = 4.55; p = 0.0139).ConclusionEosinophil count could be used as a prognostic factor in anal HPV-positive SCC. The worse prognosis showed in HPV-positive patients with high eosinophil count is likely to derive from an unfavorable interaction between the HPV-induced immunomodulation and eosinophils, which may hamper the curative effect of RT.

The role of concomitant chemoradiotherapy versus radiation alone in T1-3N0 HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma

ObjectiveTo evaluate the role of curative intent concurrent chemoradiation (CCRT) vs radiation (RT) alone for T1-T3N0 HPV-positive and HPV-negative oropharyngeal squamous cell cancer (OPSCC). MethodsThe NCDB was queried for patients diagnosed between 2010 and 2017 with cT1-3N0M0 OPSCC treated with definitive RT or CCRT. Univariable analysis (UVA) and multivariable analysis (MVA) Cox regression analysis was performed with OS as the endpoint. Propensity score matching (PSM) 1:1 was performed. Interaction test to assess heterogeneity of treatment effect. ResultsA total of 2830 patients were queried. On MVA, CCRT was associated with improved OS for T3N0 tumors (HR 0.49; 95% CI 0.39–0.63) but not for T1N0 (HR 1.43; 95% CI 0.99–2.07) and T2N0 (HR 0.92; 95% CI 0.75–1.13). For T3 patients, CCRT improved OS for HPV-negative (HR 0.43; 95% CI 0.31–0.59) and HPV-positive tumors (HR 0.39; 95% CI 0.25–0.61). After PSM, CCRT was not statistically different to RT for patients with T1-2N0 HPV-negative tumors (HR 1.10; 95% CI 0.85–1.43; p = 0.48) and T1-2N0 HPV-positive tumors (HR 1.15; 95% CI 0.79–1.68; p = 0.45). After PSM, CCRT improved OS compared to RT alone for patients with T3N0 HPV-negative (HR 0.43; 95% CI 0.31–0.59; p < 0.01) and HPV-positive tumors (HR 0.39; 95 %CI 0.25–0.61; p < 0.01). ConclusionsCCRT is associated with improved OS in HPV-positive and HPV-negative T3N0 OPSCC. RT alone vs. CCRT demonstrated similar OS for T1-T2N0 OPSCC for both HPV negative and HPV positive tumors.

OC-0625 Differences between HPV positive and negative oropharyngeal cancer detected by Non-Gaussian IVIM

OC-0625 Differences between HPV positive and negative oropharyngeal cancer detected by Non-Gaussian IVIM

Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer

PurposeThe first aim of the trial is to study feasibility of combined programmed death protein ligand 1/cytotoxic T-lymphocyte-associated protein 4 inhibition concomitant to radiotherapy. In addition, efficacy of the entire...

Comparison of Survival of Patients With T1-2 cN0 Oropharyngeal Cancer Treated With or Without Elective Neck Dissection.

This study aimed to examine the prognostic value of elective neck dissection (END) in T1-2 clinical negative cervical lymph node (cN0 ) oropharyngeal cancer (OPC) patients. An observational retrospective study. This retrospective study included 845 patients diagnosed with T1-2 cN0 OPC during 2010-2015 from Surveillance, Epidemiology, and End Results database. Univariable and multivariable Cox regression models were used to evaluate the prognostic roles of END. Furthermore, propensity score matching was used to balance the covariates between the END and observation (OBS) groups, and subgroup analyses were conducted in the matched cohorts. The primary endpoint was overall survival (OS). Our study showed that END was an independent prognostic factor associated with a better 3-year OS compared with OBS in human papillomavirus (HPV)-positive cohort (adjusted hazard ratio [HR], 0.464; 95% confidence interval [CI], 0.235-0.916; P=.027). However, we found no prognostic value of END in HPV-negative cohort (adjusted HR, 0.837; 95% CI, 0.535-1.310; P=.435). In the subgroup analyses, we found that younger patients (≤65 years old) and patients with nontonsillar tumors in HPV-positive cohort were more likely to benefit from END, while patients with tonsillar tumors in HPV-negative cohort may benefit from END. We found that patients with HPV-positive T1-2 cN0 OPC could benefit from END in terms of OS, especially younger patients and those with nontonsillar tumors. Patients with HPV-negative T1-2 cN0 OPC could not benefit from END in terms of OS, while those with tonsillar tumors may benefit from END. 3 Laryngoscope, 132:1205-1212, 2022.

Serum Lactate Dehydrogenase is a Predictive Biomarker in Oropharyngeal Cancer Patients Undergoing Radiotherapy

<h3>Purpose/Objective(s)</h3> The present study aimed to evaluate prognostic factors, particularly with respect to their role in establishing distinct prognostic subsets of human papillomavirus (HPV)-positive and -negative oropharyngeal cancer (OPC). <h3>Materials/Methods</h3> This study retrospectively evaluated 101 patients with OPC who underwent radiotherapy (RT) alone or chemoradiotherapy (CRT) at our institution between August 2008 and December 2018. Whole neck RT (44.0-50.0 Gy/22-25 fractions) was delivered by intensity-modulated RT (IMRT), followed by boost IMRT to high-risk clinical target volume (total dose of 70.0 Gy/35 fractions). Seventy patients (69.3%) received concurrent chemotherapy. Clinical factors which were potentially associated with prognosis were analyzed. Receiver-operating characteristic curve analysis was adopted to determine the most appropriate cut-off points of hematological biomarkers including the serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/ albumin ratio (CRP/Alb). <h3>Results</h3> The median follow-up period of the surviving patients was 68 (range; 8-164) months. The 5-year overall survival rate were 69.8%. Univariate analyses revealed that poor survival was associated with gender of male, smoking≥30 pack years, Eastern Cooperative Oncology Group performance status≥1, tumor-node-metastasis (TNM) stage of III-IV (8th edition), HPV-negative, LDH≥202, CRP/Alb≥0.15, LMR < 2.90. In multivariate analyses, poor survival was independently correlated with smoking ≥30 pack years (<i>P</i> < 0.01), LDH ≥202 (<i>P</i> = 0.02). Patients were divided into two groups according to HPV status as HPV-positive and negative OPC and potential prognostic factors were assessed in univariate analyses. In HPV-positive OPC patients, poor survival was significantly associated with smoking ≥30 pack years (<i>P</i> = 0.03), LDH ≥202 (<i>P</i> = 0.04), and LMR < 2.90 (<i>P</i> < 0.01). In HPV-negative OPC patients, gender of male (<i>P</i> < 0.01), smoking ≥30 pack years (<i>P</i> < 0.01), LDH ≥202 (<i>P</i> < 0.01), and CRP/Alb ≥0.15 (<i>P</i> = 0.01) were significant predictors of poor survival. <h3>Conclusion</h3> The present study revealed that high LDH levels predicted poor survival after definitive radiotherapy in both HPV-positive and HPV-negative OPC patients. High LDH levels were stronger poor prognostic factor than HPV status and TNM stage in this study.

Cancer Stem Cells in Oropharyngeal Cancer.

Simple SummaryAlthough there has been improvement in our understanding about cancer stem cells recently, we still don’t know much about cancer stem cells of oropharyngeal cancer. Lack of knowledge solely on oropharyngeal cancer together with the information of human papilloma virus status, which is a specific factor of prognosis in oropharyngeal cancer, hardens to elucidate the distinction of the underlying mechanisms of cancer stem cell behavior. To proceed to an effective and durable therapy in oropharyngeal cancer it is necessary to reveal cancer stem cell function and related factors like its plasticity, niche, and pathways. Therefore in this review we aimed to contribute to this emerging area by focusing on the current literature and future prospects.Oropharyngeal cancer (OPC), which is a common type of head and neck squamous cell carcinoma (HNSCC), is associated with tobacco and alcohol use, and human papillomavirus (HPV) infection. Underlying mechanisms and as a result prognosis of the HPV-positive and HPV-negative OPC patients are different. Like stem cells, the ability of self-renewal and differentiate, cancer stem cells (CSCs) have roles in tumor invasion, metastasis, drug resistance, and recurrence after therapy. Research revealed their roles to some extent in all of these processes but there are still many unresolved points to connect to CSC-targeted therapy. In this review, we will focus on what we currently know about CSCs of OPC and limitations of our current knowledge. We will present perspectives that will broaden our understanding and recent literature which may connect to therapy.

Serum lactate dehydrogenase is a predictive biomarker in patients with oropharyngeal cancer undergoing radiotherapy: Retrospective study on predictive factors.

BackgroundThe present study aimed to evaluate the prognostic factors in human papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal cancer (OPC) treated with definitive radiotherapy.MethodsWe retrospectively evaluated 101 patients with OPC who underwent definitive radiotherapy between 2008 and 2018.ResultsThe median follow‐up period of the surviving patients was 68 months (range, 8–164 months). The 5‐year overall survival rate was 69.8%. Univariate analyses revealed that poor survival was associated with male sex, smoking ≥30 pack‐years, Eastern Cooperative Oncology Group performance status ≥1, tumor‐node‐metastasis (TNM) stage III‐IV (8th edition), HPV‐negativity, serum lactate dehydrogenase (LDH) ≥202, C‐reactive protein/albumin ratio ≥0.15, and lymphocyte‐to‐monocyte ratio <2.90. In multivariate analyses, poor survival was independently correlated with smoking ≥30 pack‐years (p < 0.01) and LDH ≥202 (p = 0.02).ConclusionsThe present study suggested that high LDH levels predicted poor survival after definitive radiotherapy for patients with both HPV‐positive and HPV‐negative OPC.