Human Papillomavirus Positive Oropharyngeal Research Articles

Close Margins After Transoral Robotic Surgery for Human Papillomavirus–Positive Oropharyngeal Carcinoma: A Review of the Literature and Practical Recommendations

The purpose of this article is to summarize the literature and practical recommendations from experienced centers for close margins after transoral robotic surgery for human papillomavirus–positive oropharyngeal carcinoma.

Does Bulky Adenopathy in Human Papilloma Virus-Positive Oropharyngeal Squamous Cell Carcinoma Require a Planned Post-Treatment Neck Dissection for Occult Residual Disease?

A planned neck dissection was traditionally considered for a large nodal disease after definitive chemoradiation, yet controversy exists for the human papilloma virus-positive oropharyngeal squamous cell carcinoma (HPV OPSCC). We aimed to measure the frequency of persistent occult neck disease in planned neck dissection for HPV OPSCC presenting with a large (≥3.0cm) nodal burden. We designed a retrospective cohort study at a single tertiary referral institution. The study population was sampled from 2006 to 2018 and subjects with HPV OPSCC and adenopathy ≥3.0cm. Inclusion criteria encompassed subjects who completed primary chemoradiation therapy (CRT) or primary radiation therapy (RT), and subsequently underwent a planned neck dissection. We excluded subjects who did not complete therapy or had less than 1-year follow-up. Our primary predictor variable was the size of cervical adenopathy on presentation (3.0-3.9cm, 4.0-4.9cm, 5.0-5.9cm, and ≥6.0cm). Our primary outcome of interest was the presence of disease based on the histopathology review. Other variables included the demographics, primary treatment with CRT or RT, and post-treatment clinical or radiographic evidence of disease. Chi-square testing was used to compare rates of persistent disease, with varying sizes of cervical adenopathy on presentation. The alpha level for statistical significance was set at 0.05. A total of 86 subjects were analyzed, with forty-one females and forty-five males, ranging from 36 to 77years (mean 54.6years). From the total study sample, 35% showed persistent disease, and 67% of those subjects had occult disease at the time of planned neck dissection. Greater than 20% of subjects had persistent disease when the nodal burden was ≥3.0cm at presentation. Furthermore, there was a statistically significant difference in the rates of persistent microscopic disease among subjects with nodal burden of different sizes based on chi-square testing (P=.01, χ2=10.66). Our data suggest that subjects with HPV OPSCC presenting with a nodal burden ≥3.0cm are likely to have 23% chance of persistent occult neck disease after primary CRT or RT. These findings may support the routine treatment of these subjects with a planned neck dissection after initial therapy to confirm or surgically complete disease eradication.

Radiation Dose and Volume De-Escalation for High-Risk HPV Positive Oropharyngeal Cancer

<h3>Purpose/Objective(s)</h3> Human papillomavirus (HPV) associated oropharyngeal cancers (HPV+OPC) have a favorable prognosis with standard of care treatment paradigms. Recently published and ongoing clinical trials are investigating therapy de-escalation for patients with HPV+OPC with low-risk features with promising results, but largely exclude high risk (HR) patients. This is a secondary pooled analysis reporting outcomes of patients with HR HPV+OPC treated on consecutive prospective response-adaptive de-escalation trials. <h3>Materials/Methods</h3> Patients meeting HR criteria treated on the prospective phase II trials (NCT02258659, NCT03107182) as well as on a prospective cohort registry were included for analysis. HR criteria were defined by the NRG-HN005 exclusion criteria (T4, N2c-N3 (AJCC 7th ed.), and/or > 10 pack year smoking history). Patients were treated with induction chemo- or chemoimmunotherapy followed by RECIST 1.1 response adapted volume and dose de-escalated definitive chemoradiation. Patients with ≥ 50% response to induction therapy were treated either to 45 Gy in 1.5 Gy BID fractions with 3 cycles of TFHX in a week on week off fashion or to 50 Gy in 2 Gy daily fractions delivered over 5 weeks with concurrent cisplatin. Those with < 50% response received standard dose chemoradiotherapy. Descriptive statistics were used to summarize patient characteristics. Survival was estimated using the Kaplan Meier method for progression free survival (PFS), locoregional PFS (LRPFS), and overall survival (OS). Log rank analysis was used to investigate association between the number of NRG risk factors (RF) (1 vs > 1 RF) and LRPFS. <h3>Results</h3> 80 patients met HR criteria and were evaluable (15 registry patients). Median follow up was 38.5 (IQR 27.25-61.25) months. 60% smoked > 10 pack years. 25% of patients had T4 and 45% had N2c-N3 disease. 72.5%, 25%, and 2.5% had 1, 2, and 3 NRG RF, respectively. 56 of 80 (70%) patients were de-escalated. 3-year PFS, OS, and LRPFS was 92.9%, 93.5%, and 94.7%, respectively. Locoregional failure (LRF) was 1.7% in patients with 1 NRG RF, and 13.6% LRF in patients with 2 or 3 NRG RF (p=0.0265). 3-year LRPFS was 100% for patients with N0-N2b disease and 88.6% for patients with N2c-N3 disease; all 4 locoregional failures were in-field and in patients with N2c-N3 disease who were de-escalated. Only 1 patient had an isolated distant failure. <h3>Conclusion</h3> This prospective experience demonstrates feasible dose and volume de-escalation of HPV+OPC patients with NRG HR factors. The results for the overall cohort compare favorably to prior published results. Importantly, the failure rate in de-escalated patients is in line with acceptability criteria on prior phase II de-escalation studies for low-risk patients. No patients experienced regional out-of-field failures and distant failure rates were low in a traditionally HR population. Our pooled results call for renewed cooperative group focus on trial design for radiation dose de-escalation for HPV+ patients with higher-risk disease features.

Association of Intraoperative Frozen Section Controls With Improved Margin Assessment During Transoral Robotic Surgery for Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma

Intraoperative margin assessment is an important technique for ensuring complete tumor resection in malignant cancers. However, in patients undergoing transoral robotic surgery (TORS) for oropharyngeal carcinomas, tissue artifact may provide pathologic uncertainty. To assess the benefit of providing frozen section control samples ("positive tumor biopsies") for use during intraoperative margin assessment for patients undergoing TORS for human papillomavirus (HPV)-16-positive oropharyngeal squamous cell carcinoma (OPSCC). In this cohort study, patients receiving curative-intent TORS for biopsy-proven HPV-16-positive OPSCC performed by a single attending surgeon (A.H.M.) at Ronald Reagan UCLA Medical Center from 2017 to 2021 were included in a retrospective data analysis. Exclusion criteria included HPV-negative status, participation in clinical trials, and tumors of unknown primary origin. Survival outcomes investigated included overall and disease-free survival. Adverse pathologic outcomes measured included occurrence of nondiagnostic margins and margin reversal from frozen to fixed pathology. Of the 170 patients included (mean [SD] age, 61.8 [9.9] years; 140 [82%] male), 50% of patients (n = 85) received a frozen section control. Use of a frozen section control was associated with statistically significantly improved sensitivity of intraoperative margin assessment, from 82.8% to 88.9% (difference, 6.1%; 95% CI, 3.9%-8.3%). Eleven percent (n = 18) of all tumors evaluated exhibited at least 1 nondiagnostic intraoperative margin, and 11% (n = 18) experienced margin reversal from frozen to fixed pathology. In patients with nondiagnostic margins, use of frozen section controls was associated with statistically significantly reduced time spent in the operating room (Cohen d, 1.14; 95% CI, 0.12-2.14). In this cohort study, frozen intraoperative margins assessed during TORS resections of HPV-16-positive OPSCC were diagnostically challenging. Adverse pathologic outcomes, such as margin status reversal from positive on frozen pathology to negative on formal analysis, were common. Providing intraoperative frozen section control biopsies may offer clarity in cases with nondiagnostic margins, reducing the need for additional sampling and time spent in the operating room.

Long-Term Toxic Effects, Swallow Function, and Quality of Life on MC1273: A Phase 2 Study of Dose De-escalation for Adjuvant Chemoradiation in Human Papillomavirus-Positive Oropharyngeal Cancer

Patients with human papillomavirus oropharyngeal cancer are highly curable but risk significant long-term toxic effects with standard therapy. This study investigated a de-escalation strategy of decreased adjuvant radiation therapy and chemotherapy after transoral robotic surgery, and reports on long-term functional and quality of life (QOL) outcomes. Eligible patients had a p16-positive oropharyngeal cancer and ≤10 pack-year smoking history and underwent surgery followed by treatment with either 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks with weekly docetaxel (15 mg/m2) if they had intermediate pathologic risk factors or 36 Gy in 1.8-Gy fractions twice per day over 2 weeks with the same chemotherapy if they had extranodal extension. Toxic effects, swallow function, and QOL were measured longitudinally. Seventy-nine patients (89.9% male) were treated and eligible for toxic effect and functional evaluation. Dry mouth was the most common grade 1 toxic effect at 1 year (55.6%), 2 years (53.3%), and 3 years (49.2%). The cumulative rates of grade 2 toxic effects at 1, 2, and 3 years were 1.4%, 6.7%, and 6.8%, respectively. There were only 2 grade 3 toxic effects at ≥1 year, including a grade 3 fatigue at 2.5 years, and a grade 3 superficial soft tissue fibrosis at 4 years. There were no grade 4 to 5 toxic effects. No patients were percutaneous endoscopic gastrostomy-dependent. Swallow function improved by 12 months posttreatment. QOL improved over time by all measurement tools and most patients returned to baseline level of function and QOL. De-escalated adjuvant therapy for select patients with human papillomavirus oropharyngeal cancer resulted in low rates of long-term toxic effects, excellent swallow outcomes, and preservation of global and xerostomia-related QOL.

Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus-Positive Oropharyngeal Carcinoma.

PURPOSEUnder common therapeutic regimens, the prognosis of human papillomavirus (HPV)–positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8th edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models.METHODSPatients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model.RESULTSThe study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster (P = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster.CONCLUSIONThe rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.

Insurance Status as a Predictor of Treatment in Human Papillomavirus Positive Oropharyngeal Cancer.

The link between human papillomavirus (HPV) and oropharyngeal cancer (OPC) is well known. Locally advanced, HPV-positive OPC (HPV OPC) can be treated with either chemoradiation or primary surgery with or without adjuvant therapy. Head and neck cancer patients with government insurance or uninsured have been shown to have worse prognosis than similar patients with private insurance. In this study, we aimed to determine if insurance status would predict treatment modality in patients with HPV OPC. A retrospective analysis using the National Cancer Database (NCDB). The National Cancer Database was used to identify patients with HPV OPC who underwent primary surgery or primary chemoradiation from 2010-2015. Insurance status was categorized as government, private, or no insurance. The relationship between insurance status and treatment was investigated using Chi square and multivariate regression models. Kaplan-Meier analyses were performed comparing overall survival (OS) by insurance status. There were 10,606 patients were included. There was a statistically significant correlation between insurance status and primary treatment modality for HPV OPC (P < .001). Patients with government insurance were 19.3% less likely to undergo surgery and uninsured patients were 36.9% less likely to undergo primary surgery when compared to those with private insurance (P < .001), even after correcting for TNM stage in multivariate analysis. There was an improved 5-year OS for patients with private insurance (86.6%) versus both government insurance (68.4%) and no insurance (69.9%) (P < .001). Patients with private insurance are more likely to undergo primary surgery in HPV OPC and have improved overall survival. 4 Laryngoscope, 131:776-781, 2021.

Dose and Volume De-Escalation for Human Papillomavirus–Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes

To report functional outcomes for patients with human papillomavirus-positive oropharyngeal cancer treated on a phase 2 protocol of risk- and induction chemotherapy response-adapted dose and volume de-escalated radiation therapy (RT)/chemoradiation (CRT). Patients were stratified as low risk (LR) or high risk (HR) according to T/N-stage and smoking history. Induction chemotherapy was followed by radiographic response assessment. LR patients with ≥50% response received 50 Gy RT (RT50), whereas LR patients with 30% to 50% response or HR patients with ≥50% response received 45 Gy CRT (CRT45). All other patients received 75 Gy CRT (CRT75) with RT limited to the first echelon of uninvolved nodes. Pre- and post-RT/CRT modified barium swallow studies were performed. Percutaneous endoscopic gastrostomy (PEG) tube placement, body mass index (BMI), and narcotic use were recorded. Statistical comparisons used linear or logistic regression, the Mann-Whitney U test, the χ2 test, or Fisher's exact test as appropriate. Twenty-eight LR and 34 HR patients were enrolled; 49 completed RT50/CRT45 and 11 completed CRT75. PEG-tube dependency at the end of RT/CRT and 3 months post-RT/CRT significantly differed according to risk and treatment groups (all P < .05). Treatment intensity was independently associated with 3-month PEG status while adjusting for risk group (P = .002). The CRT75 group had a median -8.42% change from baseline BMI at 1 year post-RT/CRT versus -2.54% for the RT50/CRT45 group (P = .01). At the end of RT/CRT, CRT75 patients were less likely to tolerate a normal diet, more likely to have swallowing performance status scale scores ≥4, more likely to have Rosenbek's penetration-aspiration scores ≥7, more likely to have developed trismus, and more likely to require narcotics >2 months (all P < .05). Induction chemotherapy followed by risk- and response-adapted dose and volume de-escalated RT/CRT is associated with clinically meaningful functional outcomes including (1) improved swallowing function, (2) higher BMI, and (3) shorter narcotic use for patients receiving de-escalation.

Deintensification of Adjuvant Treatment After Transoral Surgery in Patients With Human Papillomavirus-Positive Oropharyngeal Cancer: The Conception of the PATHOS Study and Its Development.

PATHOS is a phase II/III randomized controlled trial (RCT) of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery (TOS) for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). The study opened in the UK in October 2015 and, after successful recruitment into the phase II, transitioned into phase III in the autumn of 2018. PATHOS aims to establish whether the de-intensification of adjuvant treatment in patients with favorable prognosis HPV-positive OPSCC will confer improved swallowing outcomes, whilst maintaining high rates of cure. In this article, we will outline the rationale for the study and how it aims to answer fundamentally important questions about the safety, effectiveness and functional outcomes of minimally invasive TOS techniques followed by adjuvant radiotherapy (RT) or chemo-radiotherapy (CRT) in this patient population.

Educational Case: Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1

Patterns of Outcome in Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma Treated Primarily with Radical Radiotherapy

Introduction: The aims of this study were to determine patterns of outcome and prognostic factors in human papilloma virus positive oropharyngeal squamous cell carcinoma (OPSCC+) treated primarily with radical radiotherapy. Materials and methods: We identified 54 patients at a tertiary hospital in South Australia who received treatment with curative intent for OPSCC+ with radical radiotherapy ± chemotherapy or cetuximab from 1st January, 2010 to 31st March, 2017. We explored the effect of patient, tumour and radiotherapy factors on treatment outcomes. The primary endpoint was overall survival and the secondary endpoint was disease-free survival. Results: The median age was 59, with most patients being male (82%). The majority had advanced disease (89% stage IV). The median follow-up was 22.5 months. The one-year and two-year overall survival and disease-free survival rates were 89% and 79% and 77% and 68% respectively. Active smoking during radiotherapy was associated with trends to shortened overall survival (p=0.084) and reduced time to recurrence (p˃0.1). However, there was no statistically significant relationship between any other patient, tumour or treatment factors and disease-free or overall survival. Discussion: Despite advanced stage at presentation, radiotherapy ± concurrent systemic therapy results in favorable outcomes for OPSCC+. Active smoking during radiotherapy may compromise overall survival. We strongly recommend smoking cessation prior to commencing radiotherapy for OPSCC+. In addition, we note that smokers involved in de-intensification trials may be at increased risk of poor outcomes.

Decreasing Utilization of Concurrent Chemotherapy in Human Papillomavirus-Positive Oropharyngeal Cancer: Analysis of National Patterns of Care

Decreasing Utilization of Concurrent Chemotherapy in Human Papillomavirus-Positive Oropharyngeal Cancer: Analysis of National Patterns of Care

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Patients with Human Papillomavirus-Positive Oropharyngeal Cancer.

Objective To investigate the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) for human papillomavirus-positive oropharyngeal cancer (HPV+ OPC). Study Design Retrospective institutional database analysis. Setting Tertiary referral medical center. Material and Methods In total, 104 patients with HPV+ OPC were enrolled. From the blood laboratory data checked within 4 weeks before initiation of primary treatment, NLR was calculated. The association between clinicopathological characteristics and NLR was analyzed, and the prognostic role was evaluated based on overall survival (OS) and disease-free survival (DFS). Results According to the cutoff value (2.42) for NLR, the patients were classified into the low NLR group (n = 61) or the high NLR group (n = 43). High NLR was associated with a higher rate of advanced T classification ( P = .007) and diabetes mellitus ( P = .01). The proportion of surgery-based treatment was lower in the high NLR group (20.9% vs 42.6%, P = .02). The high NLR group showed a lower 5-year OS rate (85.3% vs 96.3%, P = .09) and a lower 5-year DFS rate (68.1% vs 94.7%, P = .01) than those in the low NLR group. Multivariate analysis showed that advanced N classification was a significant predictor for worse 5-year OS (hazard ratio [HR], 17.40; 95% confidence interval [CI], 2.36-128.29) and that both advanced N classification (HR, 7.78; 95% CI, 2.33-25.93) and high NLR (HR, 4.16; 95% CI, 1.24-13.95) were important prognosticators for worse 5-year DFS. Conclusion Elevated pretreatment NLR was associated with poor DFS in patients with HPV+ OPC.

Personalized Medicine and the Contradictions and Limits of First-Generation Deescalation Trials in Patients With Human Papillomavirus–Positive Oropharyngeal Cancer

Personalized Medicine and the Contradictions and Limits of First-Generation Deescalation Trials in Patients With Human Papillomavirus–Positive Oropharyngeal Cancer

Imbalance Between Clinical and Pathologic Staging in the Updated American Joint Commission on Cancer Staging System for Human Papillomavirus–Positive Oropharyngeal Cancer

Imbalance Between Clinical and Pathologic Staging in the Updated American Joint Commission on Cancer Staging System for Human Papillomavirus–Positive Oropharyngeal Cancer

Functional Outcomes After De-escalated Chemoradiation Therapy for Human Papillomavirus–Positive Oropharyngeal Cancer: Secondary Analysis of a Phase 2 Trial

To analyze functional outcomes for patients treated on a phase 2 trial of de-escalated chemoradiation therapy for human papillomavirus-positive oropharyngeal cancer. Patient eligibility included p16-positive, stage III or IV oropharyngeal squamous cell carcinoma and a Zubrod performance status of 0 to 1. Treatment was induction chemotherapy with paclitaxel, 175mg/m2, and carboplatin, area under the curve (AUC) of 6 mg/ml/min, for 2 cycles every 21days, followed by concurrent paclitaxel, 30mg/m2, every 7days with dose-reduced radiation therapy of 54 or 60Gy.Trends in body weight and body mass index (BMI) were analyzed with gastrostomy tube and narcotic use rates. Functional outcomes were assessed using the University of Washington Quality of Life Scale and the Functional Assessment of Cancer Therapy-Head and Neck Scale. Forty-five patients were registered, of whom 40 were evaluable. Only 1 patient had a BMI deemed unhealthy at the completion of treatment. For the 15 patients (38%) with a normal BMI (18-25kg/m2) before treatment, recovery back to baseline occurred at approximately 18months (average BMI, 23.2kg/m2 vs 22.3kg/m2; P=.09). In 2 patients (5%), gastrostomy tubes were placed during treatment. No patient was enteral feeding tube-dependent at 6months after treatment. Ninety-five percent of patients tolerated a normal regular diet at last follow-up. De-escalated chemoradiation therapy may improve functional outcomes as indicated by the relatively low incidence of gastrostomy tube placement and long-term dysphagia. In patients with a normal BMI prior to chemoradiation therapy, BMI recovered to baseline levels.

Prospective In Silico Study of the Feasibility and Dosimetric Advantages of MRI-Guided Dose Adaptation for Human Papillomavirus Positive Oropharyngeal Cancer Patients Compared With Standard IMRT

We aim to determine the feasibility and dosimetric benefits of a novel MRI-guided IMRT dose-adaption strategy for human papillomavirus positive (HPV+) oropharyngeal carcinoma (OPC). Patients with locally advanced HPV+ OPC were consented. Pretreatment and biweekly in-treatment serial MRIs were acquired using RT immobilization setup. The initial gross tumor volume (GTVinitial) was manually segmented using MRI then propagated to the registered simulation CT. CTVinitial was defined as GTVinitial+6-8mm to incorporate high-risk subclinical disease. For each patient, two IMRT plans were created (i.e. standard and adaptive). The prescription dose for the standard plans was 2.12 Gy for 33 fractions to the PTVinitial (CTVinitial+3mm). For adaptive plan, a new GTVadaptive was segmented on serial MRIs in case of a detectable tumor shrinkage, then a new CTVadaptive was generated. The prescription dose to PTVadaptive (CTVadaptive+3mm) was 2.12 Gy/fx to allow for maximum dose to the residual disease. Prescription dose for any previously involved volumes was 1.52 Gy/fx to ensure a floor dose of 50.16 Gy to any region ever deemed to have been directly involved with tumor. All elective nodal volumes were encompassed in CTVelective, and prescribed 1.52 Gy/fx for a total of 50.16 Gy. Organs at risk (OARs) were auto-segmented using a validated atlas-based autosegmentation software. Dosimetric parameters of OARs were recorded for standard vs adaptive plans then the normal tissue complication probability (NTCP) for toxicity endpoints were calculated using literature-derived multivariate logistic regression models. Five patients were included, 3 men and 2 women. Median age was 58 years. Three tumors originated at the tonsillar fossa and two at the base of tongue. The average dose to 95% of PTVinitial volume was 70.6 Gy (SD, 0.5) for standard plans vs 59.5 Gy (SD, 2.0) for adaptive plans. Results showed the majority of OARs had decrease in dosimetric parameters using adaptive compared with standard plans particularly for swallowing-related structures, as illustrated in table 1. The average reduction of the probability of developing dysphagia≥ grade 2 and feeding tube persistence at 6-month was 11% and 4%, respectively. The probability of developing hypothyroidism at 2-year post-treatment was also reduced by average 5% while the probability of xerostomia at 1-year was only reduced by average 1% for adaptive plans compared with standard IMRT. This in silico results showed the suggested adaptive approach is technically feasible, safe, and advantageous in reducing dose to OARs specially swallowing musculature, thus reducing the NTCP of dysphagia≥ grade 2 and feeding tube persistence at 6-month post-treatment.Abstract 3666; Table 1OARMean dose Standard (Gy)Mean dose Adaptive (Gy)Supraglottis5346SPC6358MPC5248IPC3532Mylogeiohyoid3833Genioglossus5247Oral cavity4238Soft palate5549Ipsilat. parotid3027Contralat. parotid1716Brain Stem118Thyroid gland3633 Open table in a new tab

Functional Outcomes after De-escalated Chemoradiation for Human Papillomavirus-Positive Oropharyngeal Cancer: Findings from a Phase 2 Trial

Functional Outcomes after De-escalated Chemoradiation for Human Papillomavirus-Positive Oropharyngeal Cancer: Findings from a Phase 2 Trial

E6 and E7 Antibody Levels Are Potential Biomarkers of Recurrence in Patients with Advanced-Stage Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma.

Purpose: There is a paucity of biomarkers to predict failure in human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) following curative therapy. E6/E7 viral oncoproteins are constitutively expressed in HPV+ tumors and highly immunogenic, resulting in readily detected serum antibodies. The purpose of this study is to determine whether serum E6 and E7 antibody levels can potentially serve as a biomarker of recurrence in patients with HPV+OPSCC.Experimental Design: We evaluated E6/E7 antibody levels in patients with previously untreated, advanced stage (III, IVa-b), HPV+OPSCC receiving definitive chemoradiation under a uniform protocol from 2003 to 2010. Baseline and longitudinal serum samples were obtained from our archived repository. E6/E7 serum levels were measured using a glutathione-S-transferase capture ELISA and quantified by approximating the area under the dilution curve, and were analyzed using ANOVA and linear mixed model for longitudinal analysis.Results: We compared 22 HPV+OPSCC patients who developed recurrence with 30 patients who remained disease-free. There were no differences in T classification, N classification, disease subsite, or smoking status between the groups. In a longitudinal analysis, recurrent patients had significantly higher E6 and E7 serum antibody levels than the nonrecurrent patients over the follow-up period (P = 0.02 and P = 0.002, respectively). Patients who recurred had a lower clearance of E7 antibody than patients who remained disease-free (P = 0.0016).Conclusions: Patients with HPV+OPSCC whose disease recurs have a lower clearance of E6 and E7 antibodies than patients who do not have recurrence. The ratio of E7 antibody at disease recurrence compared with baseline is potentially a clinically significant measurement of disease status in HPV+OPSCC. Clin Cancer Res; 23(11); 2723-9. ©2016 AACR.

Human Papilloma Virus-positive Oropharyngeal Squamous Cell Carcinoma in the Elderly.

Elderly patients with HPV+ oropharyngeal cancer (OPC) represent an understudied cohort of the HPV epidemic. We aimed to investigate the clinical presentation, treatment tolerability and outcomes in patient's ≥65 years old with HPV+ OPC. We identified all patients aged 65 and older treated at our Institution with HPV+ OPC and analyzed patient demographics, disease characteristics, treatment modalities, toxicities, treatment failures, and survival. Charlson comorbidity index was calculated for each patient. 43 patients were identified with a mean age of median age was 70.0 (range 65-86). The mean Charlson comorbidity index score for the cohort was 5.2. In total, 72.1% of patients received what was considered standard-of-care based on stage and pathological features. Nine point three percent of patients required RT-related treatment breaks with the majority being women (75%). Three-year actuarial overall survival was 85.5% (95% CI: 71.4%-100%) and 3-year disease-free survival was 67.3% (95% CI: 49.7-91.0%). This study presented one of the largest series to date evaluating HPV-related OPC in patients ≥65. Elderly individuals with HPV+ OPC have favorable overall survival with high treatment tolerability independent of Charlson co-morbidity score. Elderly patients should be considered for stage-appropriate care with omission of specific therapies based on absolute contraindications and patient preference, but not assumptions regarding tolerability.