HPV-positive Oropharyngeal Cancer Patients Research Articles

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 < 0.001), irrespective of HPV status. All have received sufficient IC with a median RDI of 80% or more in both age < 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.

Salivary micro RNAs as biomarkers for oropharyngeal cancer.

Despite the rising incidence, particularly of the human papillomavirus (HPV)-associated fraction of oropharyngeal cancer (OPC), there are no early detection methods for OPC. Considering the close association between saliva and head and neck cancers, this study was designed to investigate salivary micro RNA (miRNAs) associated with OPC, especially focusing on HPV-positive OPC. Saliva was collected from OPC patients at diagnosis and patients were clinically followed up ≤5 years. Salivary small RNA isolated from HPV-positive OPC patients (N = 6), and HPV-positive (N = 4) and negative controls (N = 6) were analysed by next-generation sequencing to identify dysregulated miRNAs. Discovered miRNAs were validated by quantitative PCR using two different assays in a separate cohort of patients (OPC = 91, controls = 92). The relative expression was calculated considering SNORD-96A as the normalizer. Candidate miRNAs with diagnostic and prognostic potential were evaluated by generalized logistic regression. A panel consisting of nine miRNAs was identified to have the best diagnostic performance to discriminate HPV-positive OPC from HPV-positive controls (AUC- validation-1 = 94.8%, validation-2 = 98%). Further, a panel consisting of six miRNAs were identified to discriminate OPC from controls regardless of the HPV status (AUC- validation-1 = 77.2%, validation-2 = 86.7%). In addition, the downregulation of hsa-miR-7-5p was significantly associated with poor overall survival of OPC patients (HR = 0.638). A panel consisting of nine miRNAs were identified for the prediction of the overall survival of the OPC patients (log-rank test-p = 0.0008). This study highlights that salivary miRNAs can play an essential role in the detection and prognostication of OPC.

Abstract 2288: Longitudinal measurement of HPV copy number in cell-free DNA predicts progression-free survival in HPV-positive oropharyngeal cancer patients

Abstract Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in global prevalence and is divided into two types dependent on association with human papillomavirus (HPV), with a more favorable prognosis in HPV+ve tumors. Assay of HPV copy number in plasma cell-free DNA (cfDNA) provides a minimally invasive method for detecting and monitoring tumor-derived HPV, with potential for enhancing clinical care. We have evaluated the utility of cfDNA droplet digital PCR (ddPCR) as a method for characterization and longitudinal monitoring of patients with OPSCC in a prospectively recruited cohort of 163 HPV+ve OPSCC patients. ddPCR assay of cfDNA for five HPV types showed overall 96.4% concordance with both p16 immunohistochemistry (IHC) and broad spectrum PCR analysis of solid tumor tissue. Longitudinal sampling in 105 HPV+ve patients, with median follow-up of 29 months, strongly predicted patient outcomes. Progression-free survival, stratified respectively by the presence or absence of detectable HPV cfDNA at a median of 13 weeks post-treatment, was 50% and 88% (p=0.001, hazard ratio 10.0 (95% CI 2.1-47.1)). In three patients sequential HPV measurement indicated cancer recurrence before the presence of clinical symptoms or detection on imaging. In two patients, greater reliance on sequential HPV measurement would have avoided surgical intervention which ultimately did not confirm disease presence. The high concordance of pre-treatment plasma cfDNA-HPV analysis with p16 IHC and HPV-PCR of solid tissue, together with the predictive value and utility of sequentially measured post-treatment cfDNA-HPV copy number, provide a compelling case for the routine use of cfDNA-HPV ddPCR in diagnostic classification and longitudinal monitoring of OPSCC. Citation Format: Martyna Joanna Adamowicz, Lara M. Carey, Christelle Robert, Arantza Esnal-Zufiaurre, Sophie J. Warlow, Robert Wescott, Kate Cuschieri, Brendan Conn, Ashley Hay, Iain J. Nixon, Timothy J. Aitman. Longitudinal measurement of HPV copy number in cell-free DNA predicts progression-free survival in HPV-positive oropharyngeal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2288.

Patient Benefit and Quality of Life after Robot-Assisted Head and Neck Surgery.

Robotic systems for head and neck surgery are at different stages of technical development and clinical application. Currently, robotic systems are predominantly used for transoral surgery of the pharynx and larynx. Robotic surgery of the neck, the thyroid, and the middle and inner ear is much less common; however, some oncological and functional outcomes have been reported. This article provides an overview of the current state of robot-assisted head and neck surgery with a special emphasis on patient benefit and postoperative quality of life (QoL). The focus is placed on the role of transoral robotic surgery (TORS) for the resection of oropharyngeal carcinomas. For this application, reported long-term outcomes show functional post-operative advantages for selected oropharyngeal cancer patients after TORS compared to open surgery and primary radiotherapy. Since TORS also plays a significant role in the context of potential therapy de-escalation for HPV-positive oropharyngeal cancer patients, ongoing trials are presented. Regarding the evaluation of the therapeutic benefit and the QoL of cancer patients, special attention has to be paid to the large degree of variability of individual patients' preferences. Influencing factors and tools for a detailed assessment of QoL parameters are therefore detailed at the beginning of this article. Notably, while some robotic systems for ear and skull base surgery are being developed in Europe, TORS systems are mainly used in North America and Asia. In Europe and Germany in particular, transoral laser microsurgery (TLM) is a well-established technology for transoral tumor resection. Future trials comparing TORS and TLM with detailed investigation of QoL parameters are therefore warranted and might contribute to identifying suitable fields for the application of the different techniques.

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.

Dose and Volume De-Escalation for Elective Nodal Regions in Patients With Human Papillomavirus (HPV)-Positive Oropharyngeal Cancer (OPC) Undergoing Curative-Intent Concurrent Chemoradiation (CCRT)

Several de-escalation strategies for HPV-associated OPC have focused on treatment de-intensification to the gross disease. We propose that by systematically reducing the volume and dose to the elective regions, toxicity can be decreased without compromising tumor control. Here we report our long-term results.Since 2010, we started our systemic de-escalation approach by first reducing the treatment volumes for the node-negative neck. Retropharyngeal, level IB, high level II, and levels IV-V nodal basins were not included in the subclinical target volume. For the node-positive neck, levels IB and V were not covered unless involved. Using this approach, we have observed high control rates. Starting March 2017, we subsequently reduced the dose to all elective regions to 30 Gy in 15 fractions for all patients with HPV-positive OPC undergoing curative CCRT. This is followed by a cone-down to the gross disease with a 3-5 mm margin delivering 40 Gy in 20 fractions. Patients were required to receive concurrent cisplatin or other chemotherapy.From March 2017 to July 2019, 276 consecutive HPV-positive OPC patients underwent CCRT. Median age was 61 (range: 34-87), 90% were male, and 26% had ≥ 15 pack-year of smoking history. Overall, 35% had cT3-4 and 24% had cN2-3 per AJCC 8th Edition. The majority (77%) received high-dose cisplatin and 81% of them had a cumulative dose of 300mg/m2. With a median follow-up of 23 months (range: 1-42), 7 patients (2.5%) developed locoregional recurrence - 6 had disease recurrence in the primary site and/or gross nodes that received 70 Gy and 1 patient had a gross nodal recurrence in the 30 Gy region due to mistargeting. All patients with gross nodal recurrence in the neck were successfully salvaged with surgery. There was no disease recurrence in the subclinical fields receiving 30 Gy or in the omitted radiation fields. Seventeen (6.2%) patients developed distant metastasis. The 2-year locoregional recurrence-free survival was 92.5%, distant metastasis-free survival 90.0%, and overall survival 94.6%. Fifty-six of the 276 patients were also enrolled on an adaptive radiotherapy protocol (NCT03096808) to study modification of the radiation treatment plan during treatment course to account for temporal variations in anatomy, with toxicities and quality-of-life (QoL) metrics evaluated at baseline and follow-up visits. Of the 56 patients on adaptive protocol, 5.8% had feeding tube placement during treatment. No patient had feeding tube dependence at 6 months after radiotherapy. At 2-year follow-up, most of the QoL metrics (pain, social contact, social eating, speech, and swallow) were comparable or superior to baseline measures except for taste and xerostomia.The systematic de-escalation strategy of volume and dose resulted in favorable locoregional control and acute toxicities profile. This regimen can be adapted for treating a wide range of HPV-associated OPC patients undergoing primary CCRT.

Human papillomavirus infection predicts a better survival rate in patients with oropharyngeal cancer.

IntroductionSquamous cell carcinoma is the most common malignant tumour occurring in the head and neck region. It is now understood that (human papillomavirus (HPV)- positive and HPV-negative diseases are two very different clinical entities associated with different outcomes. We decided to assess p16 expression status in patients with oropharyngeal cancer and retrospectively evaluate the outcomes of the treatment.Material and methodsThe evaluated group consisted of 98 consecutive patients with squamous cell carcinoma of the oropharynx treated in a combined way in Holycross Cancer Centre in Kielce in 2006–2014. For all patients p16 status was assessed based on the biological material. In 51 patients HPV infection was diagnosed. The Kaplan-Meier method was used to produce survival curves using the log-rank test and the Cox proportional hazard model was used to determine the risk factors. The following risk factors were included: HPV status (positive, negative), sex, age, smoking, histopathological grade of the tumour, clinical stage, and systemic therapy application. For HPV-positive and HPV-negative patients independent analyses were done including aforementioned factors, excluding HPV status.ResultsThe observation time for HPV-positive patients was significantly longer (p = 0.0008). Fifty-eight patients died, 40 patients are alive. Number of deaths in HPV-negative patients was statistically significantly higher (p = 0.0222). A statistically significant difference in the disease-free survival probability and overall survival probability between HPV-positive and HPV-negative patients was found (p = 0.0045 and p = 0.0037 respectively). For disease-free survival a statistically significant factor of the risk of recurrence was HPV infection (p = 0.0169). For HPV-positive patients, age (p = 0.0199) and smoking (p = 0.0353) were statistically significant risk factors of recurrence. For HPV-negative patients significant risk factors of recurrence were clinical stage (p = 0.0114) and systemic therapy application (p = 0.0271). For overall survival for the entire group statistically significant risk factors were absence of HPV infection (p = 0.0123), male sex (p = 0.0426), and age (p = 0.0311). For HPV-positive patients, age (p = 0.0096) and smoking (p = 0.0387) were statistically significant risk factors of death. For HPV-negative patients significant risk factors of death were clinical stage (p = 0.0120) and systemic therapy application (p = 0.0460).ConclusionsOur data show that HPV infection is a predictor of better disease-free and overall survival in patients with oropharyngeal cancer. For HPV-positive oropharyngeal cancer patients weekly given cisplatin with concurrent radiotherapy can be an alternative to three weekly given cisplatin considering effectiveness and early toxicity.

Developing Human Papillomavirus Education Material for HPV-Positive Oropharyngeal Cancer Patients with an Interprofessional Health Care Team and Patient Representatives

Purpose: The incidence of human papillomavirus (HPV)-related head and neck cancer now exceeds the incidence of HPV-related cervical cancer in Canada. A study conducted at our institution identified that patients were not provided with sufficient information regarding HPV-positive oropharyngeal squamous cell carcinoma (HPV-OPSCC). It was also recognized that patients and their partner felt guilt and stigma about the HPV diagnosis, which had a negative impact on their intimacy. The aim of this project was to create an educational tool to address the concerns of patients and their families with HPV-OPSCC through collaboration of an interprofessional health care team and patient representatives.

Quality of life analysis of HPV-positive oropharyngeal cancer patients in a randomized trial of reduced-dose (rdCRT) versus standard (sdCRT) chemoradiotherapy: Five-year follow-up.

6062 Background: Human papillomavirus-positive oropharyngeal cancer (HPV OPC) portends a more favorable prognosis compared to HPV-negative cases. To prevent overtreatment, long-term morbidity and deterioration in functionality and quality of life (QoL), multiple studies have focused on de-intensification techniques for HPV OPC treatment. To this end, we prospectively assessed differences in patient reported QoL in locally advanced HPV OPC patients receiving rdCRTversus sdCRT)in a randomized trial using a sequential therapy plan. Methods: Patients were enrolled between December 2012 and February 2016; received 3 cycles of induction docetaxel, cisplatin, and 5-FU; and were randomized to sdCRT (70 Gy) or rdCRT (56 Gy) with weekly carboplatin. Patients were followed for Progression Free Survival (PFS), Overall Survival (OS), and changes in QoL as assessed by the MD Anderson Dysphagia Inventory (MDADI), MD Anderson Symptom Inventory (MDASI Head and Neck), Xerostomia Questionnaire (XQ), and the European Organization for Research and Treatment of Cancer Questionnaire (EORTC QLQ-C30) with the head and neck module (EORTC HN). A mixed model ANOVA was used to estimate changes from baseline QoL to that at each follow-up timepoint and to compare the difference in QoL changes between the treatment arms. Results: We randomized 20 HPV+ locally advanced (LA) patients (median age: 56.5 yrs) to rdCRT (12 subjects) or sdCRT (8 subjects). 70% had high risk features. At a median follow-up of 81.5 mos, PFS and OS were 87.5% and 83.3% for sdCRT and rdCRT, respectively with a median OS of 76 mos in both arms. One patient in the sdCRT arm developed an HPV negative retromolar trigone squamous cell cancer in the radiation field 7 yrs after therapy. Baseline QoL was identical in the 15 patients who completed the QoL modules. Patients receiving rdCRT hadsignificantly lower declines in QoL scores at 3-6 month follow-up. At 5 yrs, differences in QoL changes all favored the rdCRT arm (Table) and two QoL scales reached statistical significance (P&lt;0.05). Conclusions: In HPV OPC patients, rdCRT resulted in comparable long-term survival and greater improvement in specific domains of QoL when compared to sdCRT. Our results support the need for a larger, long-term Phase 3 study in LA HPVOPC to assess these two treatments with respect to survival, QoL, and safety. Clinical trial information: NCT02945631. [Table: see text]

Droplet digital PCR quantification suggests that higher viral load correlates with improved survival in HPV-positive oropharyngeal tumours.

Although HPV-positive oropharyngeal cancer (OPC) patients have improved prognosis compared to HPV negative patients; there remains an HPV-positive group who have poor outcomes. Biomarkers to stratify discrete patient outcomes are thus desirable. Our objective was to analyse viral load (VL) by droplet digital PCR (ddPCR), in HPV-positive patients with OPC on whom clinical outcome data were available. In a cohort of patients that had previously tested HPV positive via conventional PCR, VL was determined using ddPCR assays for HPV16 L1 and E6 genes. VL was classed as "medium/high" if more than 5.57 copies or 8.68 copies of the HPV 16 L1 or E6 gene were detected respectively. Effect of VL on overall survival and hazard of death & disease progression was performed with adjustments made for sex, age, deprivation, smoking, alcohol consumption and stage. L1 VL ranged from 0.0014-304 gene copies per cell with a mean of 30.9; comparatively E6 VL ranged from 0.0012-356 copies per cell with a mean of 37.9. Univariate analysis showed those with a medium/high VL had a lower hazard of death; this was significant for L1 (p = 0.02) but not for E6 (p = 0.67). The ratio of E6 to L1 deviated from n = 1 in most samples but had no influence on clinical outcomes. HPV viral load may be informative for the further stratification of clinical outcomes in HPV positive OPC patients.

Treatment outcomes in oropharynx cancer patients who did not complete planned curative radiotherapy

PurposeTo evaluate outcomes in oropharyngeal cancer (OPC) patients who did not complete their planned curative radiation therapy (RT). MethodsOPC Patients who received less than planned curative RT dose between 2002 and 2016 were identified for analysis. HPV status was assessed. Radiation dose was normalized for fractionation variations using biological effective doses assuming tumor α/β = 10 Gy [BED10]. Outcomes were compared using BED10. Multivariable and univariable analysis identified OS predictors. ResultsFrom a total of 80 patients who did not complete therapy, 64 patients were eligible for analysis. RT incompletion was due to: RT side effects (n = 23), patients’ decision (n = 21), disease progression or metastases (n = 3), and other causes (n = 7). Median BED10 (Gy) was 56.2 for the HPV-positive and 58 for the HPV-negative. Three-year OS was 74% vs 13% (p < 0.001) for the HPV-positive (n = 29) and HPV-negative (n = 24), respectively. HPV-positive patients who received BED10 ≥55 had higher OS than those received BED10 <55 (94% vs 47%, p = 0.002) while no difference in OS by BED10 ≥55 vs <55 for the HPV-negative (12 vs 13%, p = NS). HPV-positive status was associated with a higher OS (HR 12.5, 95% CI, 4.54 to 33.3, p < 0.001). A total of 37 patients were available to estimate TD50 for local control assessment. TD50 (BED10) was estimated at 60.5 Gy for HPV-negative patients compared to 27.2 Gy for HPV-positive patients. ConclusionOverall, in patients with incomplete treatment, HPV-positive OPC patients demonstrated a better OS compared to HPV-negative patients. HPV-positive patients who received BED10 ≥55 have higher rates of OS.

Risk of second primary neoplasia in patients with oropharyngeal carcinoma: Role of HPV status in the outcome.

e17544 Background: Patients with HPV-positive oropharyngeal cancer (OPC) have better prognosis and a lower risk of appearance of second primary neoplasm (SPN) than HPV-negative OPC patients. The aim of our study was to analyze the risk of developing SPN in a large group of patients with OPC according to HPV status in the primary tumor and its relationship with toxic habits. Methods: This study includes patients from a prospective data-base: 484 OPC patients were treated from 1991 to 2017 for which the HPV DNA positivity was evaluated by PCR in available tumor specimens. HPV DNA positive samples were further tested for HPV E6*I mRNA detection and/or p16INK4a immunohistochemistry. The mean follow-up of patients included in the study was 4.9 years (SD 5.1 years). We estimated the incidence of SPN in all cancer sites and in cancer sites related to tobacco and alcohol consumption according to the HPV status in the primary tumor. Results: Ninety-nine (20.5%) out of 484 OPCs included in the study were HPV-related. During the follow-up period, 127 patients with HPV-negative tumors (33.0%) and 19 patients with HPV-positive tumors (19.2%) had a SPN. Considering only the tobacco/alcohol-related SPNs, 106 of the patients with HPV-negative tumors (27.5%), and 12 patients with HPV-positive tumors (12.1%) had a tobacco/alcohol-related SPN (P &lt; 0.0001). Five-year and 10-year SPN-free survival for HPV-negative versus HPV-positive OPC patients was 61.0% versus 81.5%, and 37.6% versus 73.8%, respectively (P &lt; 0.001). When restricting the analyses to tobacco/alcohol-related SPNs, the corresponding survival rates were 66.6% versus 86.8% and 45.9% versus 83.5% for 5-year and 10-year survival rates, respectively (P &lt; 0.0001). The frequency of tobacco/alcohol-related SPNs occurrence throughout the follow-up period for patients with HPV-negative OPC was 27.5%, for patients with HPV-positive tumors with a previous history of severe tobacco and/or alcohol use was 21.4%, and for patients with HPV-positive tumors without a history of severe tobacco and/or alcohol consumption it was 8.5% (P &lt; 0.0001). Conclusions: HPV status and previous toxic habits might allow classifying patients regarding the risk of tobacco/alcohol-related SPNs. HPV-related OPC patients without previous history of severe tobacco and/or alcohol use have a significant low risk of SPN development, particularly in those locations related to tobacco use or alcohol consumption

Impact of Postoperative Chemoradiation for HPV Positive Oropharyngeal Cancers with Extranodal Extension and/or Positive Margins

Level 1 evidence suggests an overall survival (OS) benefit with the addition of concurrent chemotherapy to adjuvant radiation in patients with head and neck squamous cell carcinoma (HNSCC) who have pathologic positive margins (+margin) or extra-nodal extension (ENE). It is uncertain whether this benefit persists in HPV positive oropharyngeal cancer patients with similar risk factors. We sought to analyze adjuvant patterns of care and their impact on OS in HPV positive oropharyngeal patients with high risk pathologic features. We used the National Cancer Database to select a population of surgically treated (>local excision), pathologically high risk (+margin or ENE) patients with non-metastatic, HPV positive, squamous cell carcinoma of the oropharynx who received either adjuvant radiation (aRT) or chemoradiation (aCRT). Univariable and multivariable logistic regression was used to assess predictors of the use of aCRT compared to aRT in this cohort. Univariable and multivariable Cox regression was then performed to evaluate the impact of adjuvant treatment type on OS. Age (<55, 55-64, ≥65), gender (male, female), race (White, Black, Other), Charlson-Deyo comorbidity score (0, 1, ≥2), AJCC 7th edition stage (I, II, III, IVA, IVB), facility type (non-academic, academic), high-risk feature (+margin, ENE, both), insurance (none, private, Medicaid, Medicare, other/unknown), and year of diagnosis (2010-2012, 2013-2014) were included as confounders. There were 1,638 patients who met inclusion criteria; 436 (26.6%) received aRT and 1,202 (73.4%) received aCRT. Median follow up was 42 months and median RT dose was 6600cGy. On multivariable logistic regression, stage IVA-IVB (OR 3.31-5.81, p=0.001), presence of ENE (OR 1.42, 95% CI 1.04-1.92, p=0.027) or both ENE and +margin (OR 1.69, 95% CI 1.12-2.56, p=0.013) were associated with increased likelihood of receiving aCRT. Treatment at an academic facility (OR 0.65, 95% CI 0.50-0.85, p=0.002) was associated with decreased likelihood of receiving aCRT. The 5-year survival was 87.3% with aRT and 89.9% with aCRT (p=0.469); on multivariable analysis, there were no OS difference comparing postoperative CRT to postoperative RT (HR 0.68, 95% CI 0.44-1.05, p=0.079). Although not significant, after adjustment for confounders, there was a trend towards improved OS with aCRT compared to aRT in surgically treated OPC patients with high risk features. De-escalation of adjuvant therapy in this group, especially those with multiple high risk features, should be undertaken with caution.

Evaluation of Pre- and Post-IMRT FDG-PET SUV Values for the Prediction of Tumor Control In HPV-Positive Oropharyngeal Cancer Patients

Evaluation of Pre- and Post-IMRT FDG-PET SUV Values for the Prediction of Tumor Control In HPV-Positive Oropharyngeal Cancer Patients

Modifications and recent updates in the 8th edition of tumor node metastasis staging pertaining to oropharynx and oral cavity.

Modifications and recent updates in the 8th edition of tumor node metastasis staging pertaining to oropharynx and oral cavity.

The applicability of new TNM classification for humanpapilloma virus-related oropharyngeal cancer in the 8th edition of the AJCC/UICC TNM staging system in Japan: A single-centre study

ObjectiveThe purpose of this study is to validate the applicability of new TNM classification for human papillomavirus (HPV)-related oropharyngeal cancer (OPC) in the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system in Japan. MethodsA total of 91 OPC patients treated with radiation-based therapy between November 2001 and July 2015 were analyzed retrospectively in this study. HPV infection status was evaluated using tumor p16 expression. Results40 OPC patients (44.0%) had HPV-positive disease in this study. The distribution of disease stage of HPV-positive OPC patients dramatically changed from the 7th edition to the 8th edition of AJCC/UICC TNM classification. However, neither the 8th edition nor the 7th edition of the AJCC/UICC TNM staging system could adequately predict outcomes of HPV-positive OPC patients in our patient series. On the other hand, our multivariate analysis indicated that matted nodes and age ≥63 were independent prognostic factors for progression-free survival. In addition, HPV-positive OPC patients with stage I without matted nodes showed significantly better overall and progression-free survival compared with those with stage I with matted nodes and stages II and III in the 8th edition of the AJCC/UICC TNM staging system (P=0.008, and P=0.043, respectively). ConclusionOur results suggested that matted nodes of HPV-positive OPC patients might be additionally examined to apply the 8th edition of AJCC/UICC TNM classification for more adequate predicting outcomes of HPV-positive OPC patients.

HPV-associated differential regulation of tumor metabolism in oropharyngeal head and neck cancer.

HPV-positive oropharyngeal cancer patients experience significantly lower locoregional recurrence and higher overall survival in comparison with HPV-negative patients, especially among those who received radiation therapy. The goal of the present study is to investigate the molecular mechanisms underlying the differential radiation sensitivity between HPV-negative and HPV-positive head and neck squamous cell carcinoma (HNSCC). Here, we show that HPV-negative HNSCC cells exhibit increased glucose metabolism as evidenced by increased production of lactate, while HPV-positive HNSCC cells effectively utilize mitochondrial respiration as evidenced by increased oxygen consumption. HPV-negative cells express HIF1α and its downstream mediators of glucose metabolism such as hexokinase II (HKII) and carbonic anhydrase IX (CAIX) at higher levels, while the expression level of cytochrome c oxidase (COX) was noticeably higher in HPV-positive HNSCC. In addition, the expression levels of pyruvate dehydrogenase kinases (PDKs), which inhibit pyruvate dehydrogenase activity, thereby preventing entry of pyruvate into the mitochondrial tricarboxylic acid (TCA) cycle, were much higher in HPV-negative HNSCC compared to those in HPV-positive cells. Importantly, a PDK inhibitor, dichloroacetate, effectively sensitized HPV-negative cells to irradiation. Lastly, we found positive interactions between tonsil location and HPV positivity for COX intensity and COX/HKII index ratio as determined by immunohistochemical analysis. Overall survival of patients with HNSCC at the tonsil was significantly improved with an increased COX expression. Taken together, the present study provides molecular insights into the mechanistic basis for the differential responses to radiotherapy between HPV-driven vs. spontaneous or chemically induced oropharyngeal cancer.

(P076) Sequential Boost Compared With Simultaneous Integrated Boosts for HPV Positive Oropharyngeal Cancer Patients

(P076) Sequential Boost Compared With Simultaneous Integrated Boosts for HPV Positive Oropharyngeal Cancer Patients

(P052) Small Reductions in Dose Appear Equally Effective for HPV Positive Oropharyngeal Cancer Patients

(P052) Small Reductions in Dose Appear Equally Effective for HPV Positive Oropharyngeal Cancer Patients

Pathologic Markers in Surgically Treated HPV-Associated Oropharyngeal Cancer: Retrospective Study, Systematic Review, and Meta-analysis.

Human papillomavirus-associated (HPV) oropharyngeal cancer is a unique clinical entity whose incidence is increasing. It is controversial whether traditional pathologic markers of aggressive head and neck cancer also apply in surgically treated HPV-associated disease. Retrospective study, systematic review, and meta-analysis Data Sources: PubMed and Cochrane review. PubMed and Cochrane review were searched for published articles on surgically treated HPV-associated oropharyngeal cancer. Eligible studies were included in a meta-analysis of survival using several clinicopathologic markers as predictors. Surgically treated HPV-positive oropharyngeal cancer patients at our institution were studied retrospectively and added to the meta-analysis. Eight published reports, plus our retrospective series, were included in the meta-analysis. This showed significant impact on event-free survival for T stage, nodal number, perineural invasion, and lymphovascular invasion (all P < .05) but not for N stage extracapsular extension ( P = ns). While many traditional clinico-pathologic markers of aggressive disease in head and neck cancer also impact survival in surgically treated HPV-associated oropharyngeal cancer, extracapsular extension may be less important.