Human papillomavirus infection and tumor microenvironment are associated with the microbiota in patients with oropharyngeal cancers-pilot study.

BACKGROUND: Previous microbiome studies of oropharyngeal cancer have shown that there are differences in the oral microbiota between human papillomavirus (HPV)-positive and HPV-negative patients. METHODS: We collected saliva, normal tissue, and tumor biopsies from 13 patients with oropharyngeal cancer (eight HPV-positive, five HPV-negative). We obtained basic clinical data from each patient. Extracted DNA was 16S rRNA gene sequenced. Analysis was based on HPV status and sample site using univariate, multivariate, and mixed effect regression methods. RESULTS: Multivariate analysis methods separated samples based on HPV status (Adonis, p < 0.001). Comparison of patients showed that there were significant changes in microbial richness across all sites based on HPV status (linear mixed effects regression, p = 0.0002). CONCLUSIONS: We found significant differences in overall microbial community and bacterial richness between oropharyngeal patients based on HPV status. Our results suggest that there are significant differences in the microbiome in patients with oropharyngeal cancer based on HPV status.

The importance of smoking status at diagnosis in human papillomavirus-associated oropharyngeal cancer.

BACKGROUND: Smoking status at point of diagnosis is not used in defining risk groups for human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) despite its prognostic value in head and neck cancer. METHODS: Retrospective analysis of consecutive patients treated with chemoradiotherapy between January 2005 and July 2017 was performed with multivariable analysis to explore the impact of smoking status at diagnosis (current/former/never) on overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). RESULTS: Median follow-up was 61 months. Four hundred and four patients were included. Current smokers had inferior OS versus never and former smokers [adjusted HR 2.37 (95% CI 1.26-4.45, p < 0.01) and 2.58 (95% CI 1.40-4.73, p < 0.01), respectively] and inferior PFS versus never smokers [adjusted HR 1.83 (95% CI 1.00-3.35, p = 0.04)]. Smoking status did not predict for CSS. CONCLUSION: Detailed smoking behavior should be considered in refining risk groups in HPV-associated OPC treated with radiotherapy and in future trial design eligibility and stratification.

The declining role of post-treatment neck dissection in human papillomavirus-associated oropharyngeal cancer.

BACKGROUND AND PURPOSE: Human papillomavirus-associated oropharyngeal cancer (HPV+ OPC) with regional lymph node metastases has a good prognosis following (chemo)radiation therapy (C/RT) but lymph nodes may remain detectable for several months. Delayed [18F]-Fluorodeoxyglucose positron emission tomography/computed tomography (PET) can identify patients who may avoid post-treatment neck dissection (PTND). We investigated the rate of PTND in HPV+ OPC treated with C/RT and delayed PET-directed management of the neck. MATERIALS AND METHODS: This is a retrospective cohort study from a prospectively updated institutional database. Eligible patients were treated between January 2005 and July 2017 with a minimum of 18 months follow up, had node-positive, non-distant metastatic HPV+ OPC and were treated with RT (70 Gy/35#/5 per week) with concurrent Cisplatin or Cetuximab, or accelerated RT alone (68 Gy/34#/6 per week). The primary endpoint was rate of PTND. Secondary endpoints were locoregional failure free survival (LRFFS), regional failure free survival (RFFS), distant metastatic failure free survival (DMFFS), overall survival (OS) and oropharyngeal cancer-specific survival (CSS). RESULTS: 418 patients were eligible. Nineteen patients (4.5%) received a PTND. None of the tested variables were associated with an increased risk of PTND. Five-year probabilities for LRFFS, RFFS, DMFS, OS and CSS were, 91.2% (95% CI 88.3-94.2), 93.4% (95% CI 90.8-96.0), 91.2% (95% CI 88.3-94.2), 86.4% (95% CI 83.0-90.1) and 90.2% (95% CI 87.1-93.4), respectively. CONCLUSION: In a large cohort with good median follow up and protocolized C/RT, delayed PET-directed management of the neck affords a lower rate of PTND than reported in historical series without compromising disease control and survival.

Utility of a repeat PET/CT scan in HPV-associated Oropharyngeal Cancer following incomplete nodal response from (chemo)radiotherapy.

OBJECTIVES: To assess the utility of a repeat positron emission tomography/computed tomography (PET/CT) instead of immediate neck dissection (ND) for incomplete nodal response (IR) in Human Papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC) following chemoradiotherapy/radiotherapy [(chemo)RT]. MATERIALS AND METHODS: Patients with non-distant metastatic, node positive (N+) disease treated between Jan/2005 to Jan/2016, achieved complete response at the primary with no distant relapse on a 12-week re-staging PET/CT were evaluated. Patients underwent surveillance after complete nodal response (CR). Patients with IR underwent repeat PET/CT at 16 weeks to direct neck management. Primary endpoints were CR conversion rate and subsequent regional failure following a 16-week PET/CT directed ND. Secondary endpoints were predictive values (PV) of the 12- and 16-week PET/CT for residual nodal disease, predictors for requiring the 16-week PET/CT, 5 year regional, locoregional failure free survival (FFS) and overall survival (OS). RESULTS: 235 patients were evaluated. Median follow up was 56 (range 19-60) months. 41 patients underwent 16-week re-staging PET/CT, 29 (71%) converted to CR. No subsequent regional failures occurred following a 16-week PET/CT directed ND. Positive and negative PV of the 12- and 16-week PET/CT for residual nodal disease was 12% & 98%, and 33% & 97%, respectively. N-category (AJCC/UICC 7th edition) predicted for requiring a 16-week PET/CT on univariate analysis (P-value 0.02). 5 year regional, locoregional FFS and OS was 95.8%, 93.4% and 90.8%, respectively. CONCLUSION: For N+ HPV-associated OPC achieving IR on the 12-week re-staging PET/CT following (chemo)RT, a repeat 16-week PET/CT can spare patients from unnecessary surgery.

Postoperative Concurrent Chemoradiotherapy Versus Postoperative Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: The Randomized Phase III TROG 05.01 Trial.

Purpose To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease. Secondary efficacy objectives were to compare disease-free survival and overall survival. Results Three hundred twenty-one patients were randomly assigned, with 310 patients commencing allocated treatment (radiotherapy [RT] alone, n = 157; CRT, n = 153). Two hundred thirty-eight patients (77%) had high-risk nodal disease, 59 (19%) had high-risk primary or in-transit disease, and 13 (4%) had both. Median follow-up was 60 months. Median RT dose was 60 Gy, with 84% of patients randomly assigned to CRT completing six cycles of carboplatin. The 2- and 5-year FFLRR rates were 88% (95% CI, 83% to 93%) and 83% (95% CI, 77% to 90%), respectively, for RT and 89% (95% CI, 84% to 94%) and 87% (95% CI, 81% to 93%; hazard ratio, 0.84; 95% CI, 0.46 to 1.55; P = .58), respectively, for CRT. There were no significant differences in disease-free or overall survival. Locoregional failure was the most common site of first treatment failure, with isolated distant metastases as the first site of failure seen in 7% of both arms. Treatment was well tolerated in both arms, with no observed enhancement of RT toxicity with carboplatin. Grade 3 or 4 late toxicities were infrequent. Conclusion Although surgery and postoperative RT provided excellent FFLRR, there was no observed benefit with the addition of weekly carboplatin.