Papillomavirus-associated Oropharyngeal Squamous Cell Research Articles

Etiology, diagnosis, treatment, and prevention of human papilloma virus-associated oropharyngeal squamous cell carcinoma.

Classical oropharyngeal squamous cell carcinoma (OPSCC) caused by alcohol consumption and smoking and HPV-associated OPSCC caused by human papillomavirus (HPV) infection have different etiologies, incidences, and prognoses. Therefore, the 8th American Joint committee on Cancer (AJCC) and Union for International Cancer Control (UICC) TNM classifications propose distinguishing HPV-associated OPSCC from classical OPSCC and classifying it as an independent disease. Therefore, this review provides an overview of HPV-associated OPSCC from the perspectives of epidemiology, carcinogenesis, development, diagnosis, treatment, and prevention. The incidence of HPV-associated OPSCC is increasing. Although HPV vaccination has been shown to be effective at reducing the incidence of cervical cancer, it is still unclear how it affects the incidence of HPV-associated OPSCC. Additionally, the prognosis of patients with HPV-associated OPSCC is extremely favorable compared to that of patients with classical OPSCC. Therefore, patients with HPV-associated OPSCC may undergo reduced-dose therapy, although attempts to reduce treatment intensity should be carefully planned to ensure they do not compromise oncological outcomes, and large-scale trials aimed at reducing treatment intensity are ongoing.

Prognostic stratification of HPV-associated oropharyngeal cancer based on CD103+ immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomized trials

High CD103+ intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis. We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103+ ITIC high (≥30%) versus low (<30%). High and low CD103 were compared using Cox regression adjusting for age, stage and trial. Tumor samples were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. CD103+ ITIC abundance was high in 27% of patients. The median follow-up was 3.2 years. The 3-year FFS in patients treated with CETUX/RT was 93% [95% confidence interval (CI) 79% to 98%] in high CD103 and 74% (95% CI 63% to 81%) in low CD103 [adjusted hazard ratio= 0.22 (95% CI 0.12-0.41), P < 0.001]. The 3-year overall survival in patients treated with CETUX/RT was 100% in high CD103 and 86% (95% CI 76% to 92%) in low CD103, P < 0.001. In patients treated with CIS/RT, there was no significant difference in FFS. CD103+ ITIC expression separates CETUX/RT-treated low-risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials.

Analysis of clinicopathological features of human papilloma virus-associated oropharyngeal squamous cell carcinoma

Analysis of clinicopathological features of human papilloma virus-associated oropharyngeal squamous cell carcinoma

MC1675, a Phase III Evaluation of De-Escalated Adjuvant Radiation Therapy (DART) vs. Standard Adjuvant Treatment for Human Papillomavirus Associated Oropharyngeal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> We previously reported the results of a phase II clinical trial evaluating 30-36 Gy of adjuvant radiation therapy (RT) for selected patients with HPV+ OPSCC. Herein we report the two-year results of a phase III trial comparing this 30-36 Gy regimen with standard of care (SOC) adjuvant RT. <h3>Materials/Methods</h3> All patients (pts) received transoral robotic surgery (TORS) and neck dissection for a margin negative resection. Pts with pT4 disease or who required >2 attempts to clear margins were excluded. Pts with intermediate risk factors received 30 Gy/1.5 Gy b.i.d. + docetaxel 15 mg/m² days 1 and 8, while pts with extranodal extension (ENE) simultaneously received 36 Gy/1.8 Gy b.i.d. to ENE+ nodal levels. Pts were randomized (2:1) to DART or SOC (60 Gy ± weekly cisplatin 40 mg/m²). Stratification was by risk group (intermediate risk vs ENE+) and smoking status (< vs ≥10 pack-yr). The primary endpoint was grade ≥3 AE rate ≥3 mos after RT with the study powered to have 90% power to detect a grade ≥3 AE rate reduction from 25% to 7%. Secondary endpoints were OS, LRC, PFS, and QOL. Pts received a swallow evaluation (MBSImP) before, 1 mo, and 1 yr post-RT. Pts also had QOL assessed with the FACT-HN, EORTC-HN35, and University of Michigan Xerostomia QOL Scale (XeQOLS) pre-RT and 1, 3, 12, and 24 mos post-RT. <h3>Results</h3> Accrual was from 10/16 – 8/20 (n = 194, DART: 130, SOC: 64, ENE+: 115 (59%), Non-smokers: 139 (72%), median age 59.4 yrs (37.9-81.6), male 89%. Median follow-up as of 7/21 was 25.3 mo. 1.6% DART and 27.4% SOC pts (p<0.0001) required a feeding tube. Grade ≥3 AEs at 3 months were 1.6% DART vs 7.1% SOC (p = 0.058). Swallowing function change from baseline to 1 month was superior in the DART arm (DART vs SOC, median) MBSImP: -0.3 vs -2.6 (p = 0.0155) as was baseline to 3 month QOL FACT-HN: 5.1 vs -3.2 (p = 0.0007); EORTC-HN Pain: -8.6 vs 2.5 (p = 0.0009); XeQOLS: 2.9 vs 11.7 (p = 0.0001). 2 yr statistics between DART and SOC arms were similar except for PFS on the DART/ENE+ arm (Table). PFS on the DART/ENE+ arm was driven by the pN2 cohort (AJCC 8, >4 LN). For ENE+/pN0-1 pts, (DART vs SOC) 2 yr PFS was 89.6% vs 95.8%; LRC 95.8% vs 100.0%; DMFS 96.4% vs 95.8%. For ENE+/pN2 (DART vs SOC) PFS was 42.9% vs 100%; LRC 77.0% vs 100%; DMFS 59.4% vs 100%. <h3>Conclusion</h3> DART demonstrated less toxicity, improved swallowing function and QOL when compared to SOC. DART also had excellent LRC, PFS, and OS rates, particularly in the ENE negative cohort. Caution is advised for de-escalating ENE+ pts with pN2 disease.

Long-Term Results for MC1273, A Phase II Evaluation of De-Escalated Adjuvant Radiation Therapy for Human Papillomavirus Associated Oropharyngeal Squamous Cell Carcinoma (HPV+ OPSCC)

Long-Term Results for MC1273, A Phase II Evaluation of De-Escalated Adjuvant Radiation Therapy for Human Papillomavirus Associated Oropharyngeal Squamous Cell Carcinoma (HPV+ OPSCC)

Abstract 17: Patterns of neck nodal metastases and recurrence in human papilloma virus-associated oropharyngeal squamous cell carcinoma after neck dissection

Abstract Background: The aim of this study is to address the paucity of data on the potentially unique patterns of neck nodal metastases in HPV-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC). Methods: The neck dissection (ND) specimens of varying levels of HPV+OPSCC patients at University of California-San Francisco from 2010-2016 were reviewed for the numbers and frequencies of clinically evident and occult nodes by neck level, and for those with extra-capsular spread (ECS). Smoking history (&amp;gt;10 pack-years), T status, and local, regional and distal recurrences were also assessed for possible associations with nodal metastatic behavior. Results: Sixty HPV+OPSCC patients underwent primary site trans-oral robotic surgery and 65 NDs, of which 21 (32%) were elective. Forty-three (65%) NDs were in non-smokers. Overall, the mean number of positive nodes per ND was 2.5 (range 1-9). The frequencies of at least one pathologically positive node for neck levels 1b, 2, 2a, 2b, 3, 4, and 5 were 0% (0/41), 67.7% (44/65), 43% (23/53), 13% (7/53), 27.7% (18/65), 7% (4/54), and 8% (2/23), respectively. All positive level 5 positive nodes were clinically evident preoperatively. Five of 21 (24%) elective NDs had occult disease only in levels 2A, 2B, and 3, with a mean number of positive nodes of 1.8 (range 1-3). Three of 21 (14%) elective NDs had nodes with ECS. Six of 44 (13%) therapeutic NDs had occult nodes outside the known preoperative distribution in levels 2b, 3 and 4. There were no occult 2a nodes. Smoking history, primary site, and T status were not statistically significantly associated with a differing metastatic nodal behavior. Twenty-three of 60 and 18 of 60 patients underwent adjuvant radiation and adjuvant chemoradiation, respectively. Thirteen of the 19 patients who only underwent surgery had positive lymph nodes, of which five had N1 disease and four had N2b disease. All four of N2b disease patients refused adjuvant therapy and none have had a recurrence as of follow-up (mean 28 months, range 3-51). The overall mean follow-up was 29.1 months (range 2-76 months), with 72% of patients having at least 12 months. One of 65 (1.5%) NDs developed a neck recurrence in the skin overlying level 2 in a patient in the therapeutic ND cohort who had undergone chemoradiation for ECS. No undissected neck levels developed metastatic nodal disease. Two of 60 (3%) patients developed local recurrence. No patients developed distant metastases. One patient in the cohort died of an unrelated cause. There have been no cancer-related deaths. Conclusions: For HPV+OPSCC, therapeutic NDs should encompass any levels bearing suspicious nodes and levels 2a, 2b, 3, and 4, while elective NDs should be performed and encompass at least levels 2a, 2b, and 3. ECS may be present in occult nodes. For HPV+OPSCC, these selective ND plans, followed by the indicated adjuvant treatment, is associated with a low neck recurrence rate. Citation Format: Madeleine P. Strohl, Steven J. Wang, Patrick K. Ha, Jonathan R. George, Chase M. Heaton, Ivan H. El-Sayed, Jon Mallen St Clair, William R. Ryan. Patterns of neck nodal metastases and recurrence in human papilloma virus-associated oropharyngeal squamous cell carcinoma after neck dissection [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 17.