Human Papillomavirus-associated Oropharyngeal Squamous Cell Research Articles

Intravoxel incoherent motion imaging kinetics during chemoradiotherapy for human papillomavirus-associated squamous cell carcinoma of the oropharynx: preliminary results from a prospective pilot study.

This study aims to identify the temporal kinetics of intravoxel incoherent motion (IVIM) MRI in patients with human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma. Patients were enrolled under an Institutional Review Board (IRB)-approved protocol as part of an ongoing prospective clinical trial. All patients underwent two MRI studies: a baseline scan before chemoradiotherapy and a mid-treatment scan 3-4 weeks after treatment initiation. Parametric maps representing pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) were generated. The Mann-Whitney U-test was used to assess the temporal variation of IVIM metrics. Bayesian quadratic discriminant analysis (QDA) was used to evaluate the extent to which mid-treatment changes in IVIM metrics could be combined to predict sites that would achieve complete response (CR) in multivariate analysis. Thirty-one patients were included in the final analysis with 59 lesions. Pretreatment ADC and D values of the CR lesions (n = 19) were significantly lower than those of non-CR lesions (n = 33). Mid-treatment ADC, D and f values were significantly higher (p < 0.0001) than pretreatment values for all lesions. Each increase in normalized ΔADC of size 0.1 yielded a 1.45-fold increase in the odds of CR (p < 0.0003), each increase in normalized ΔD of size 0.1 yielded a 1.53-fold increase in the odds of CR (p < 0.0002), and each unit increase in Δf yielded a 2.29-fold increase in the odds of CR (p < 0.02). Combined ΔD and ΔADC were integrated into a multivariate prediction model and attained an AUC of 0.87 (95% confidence interval: 0.79, 0.96), as well as a sensitivity of 0.63, specificity of 0.85 and accuracy of 0.78, under leave-one-out cross-validation. In conclusion, IVIM is feasible and potentially useful in the prediction and assessment of the early response of HPV+ oropharyngeal squamous cell carcinoma to chemoradiotherapy.

Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

To perform a prospective, multi-institutional, phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus-associated oropharyngeal squamous cell carcinoma. The major inclusion criteria were: (1) T0 to T3, N0 to N2c, M0; (2) human papillomavirus or p16 positive; and (3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy with concurrent weekly intravenous cisplatinum (30 mg/m(2)). The primary study endpoint was pathologic complete response (pCR) rate based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless of radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and n=40, resulting in a type 1 error of 14.2%. Secondary endpoint measures included physician-reported toxicity (Common Toxicity Terminology for Adverse Events, CTCAE), patient-reported symptoms (PRO-CTCAE), and modified barium swallow studies. The study population was 43 patients. The pCR rate was 86% (37 of 43). The incidence of CTCAE grade 3/4 toxicity and PRO-CTCAE severe/very severe symptoms was as follows: mucositis 34%/45%, general pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematologic toxicities were 11%. Thirty-nine percent of patients required a feeding tube for a median of 15 weeks (range, 5-22 weeks). There were no significant differences in modified barium swallow studies before and after CRT. The pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly low-dose cisplatinum is very high in favorable-risk oropharyngeal squamous cell carcinoma, with evidence of decreased toxicity compared with standard therapies. ClinicalTrials.gov ID: NCT01530997.

Transoral Surgery Alone for Human-Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

The aim of this retrospective study was to describe the oncologic and functional results of treating oropharyngeal squamous cell carcinoma with transoral robotic surgery and neck dissection as monotherapy. A review was performed, including all patients who underwent transoral robotic surgery and neck dissection as the only means of therapy for oropharyngeal carcinoma from March 2007 to July 2009 at a single tertiary care academic medical center. We reviewed all cases with ≥24-month follow-up. Functional outcomes included tracheostomy dependence and oral feeding ability. Oncologic outcomes were stratified by human papillomavirus (HPV) status and tobacco use and included local, regional, and distant disease control, as well as disease-specific and recurrence-free survival. Eighteen patients met study criteria. Ten patients (55.6%) were able to eat orally in the immediate postoperative period, and 8 (44.4%) required a temporary nasogastric tube for a mean duration of 13.6 days (range 3 to 24 days) before returning to an oral diet. No patient required placement of a gastrostomy tube, and all patients are tracheostomy-tube-free. Among the HPV-positive nonsmokers (12/18, 66.7%), Kaplan-Meier estimated 3-year local, regional, and distant control rates were 90.9%, 100%, and 100%, respectively. Kaplan-Meier estimated disease-specific survival and recurrence-free survival were 100% and 90.9%, respectively. No complications occurred.This study suggests that carefully selected patients with HPV-positive oropharyngeal carcinoma can be effectively treated with surgery alone with excellent functional and oncologic outcomes.

Human Papillomavirus—Associated Oropharyngeal Squamous Cell Carcinomas: Primary Tumor Burden and Survival in Surgical Patients

We sought to determine whether the primary tumor burden in oropharyngeal squamous cell carcinoma is lower in tumors positive for human papillomavirus (HPV) or in tumors with a smoking- or alcohol-related cause. We retrospectively reviewed medical records of patients at our institution who had squamous cell carcinoma of the palatine tonsils, base of tongue, soft palate, or pharynx from 1995 through 2006. The patients underwent primary surgical therapy. The main outcome measures were the HPV status of tumors and nodes and the survival rates (categorized by HPV status). Of 102 treated patients, 48 (47.1%) had HPV-positive carcinomas. Primary tumor size was not significantly different between HPV-positive and HPV-negative tumors (median, 2.5 versus 2.0 cm; p = 0.43). Patients with HPV had a higher prevalence of neck nodal metastases (35% versus 11%; p = 0.003) and high-grade lesions (83% versus 64%; p = 0.03). Primary tumor burden was not associated with HPV status. Patients with HPV-positive oropharyngeal squamous cell carcinomas had a higher prevalence of neck nodal metastases and high-grade lesions.

Advances in Chemotherapy Options for Head and Neck Cancer

The role of chemotherapy in the management of head and neck squamous cell cancers continues to evolve. Concurrent chemotherapy and radiation represents a standard treatment option for organ preservation in larynx and hypopharynx squamous cell carcinomas, unresectable locally advanced head and neck cancer, nasopharyngeal cancer, and post-operative therapy of high-risk resected disease. Chemotherapeutic agents and their combinations have known activity in metastatic disease and are frequently used for palliation. Emerging therapeutic approaches have been fueled by the observed shift in the pattern of disease recurrence after definitive therapy and the development of molecular targeted agents with disease activity. The recognition of human papillomavirus-associated oropharyngeal squamous cell carcinoma as a distinct clinical entity among head and neck cancers will influence the design of future clinical investigation.