The relevance of the lymph node ratio as predictor of prognosis is higher in HPV-negative than in HPV-positive oropharyngeal squamous cell carcinoma (original) (raw)

Low‐risk human papilloma virus positive oropharyngeal cancer with one positive lymph node: Equivalent outcomes in patients treated with surgery and radiation therapy versus surgery alone

Head & Neck

Background-For HPV+ oropharyngeal squamous cell carcinoma (OPSCC), management recommendations for patients with a single metastatic lymph node <6 cm in diameter remain nebulous, leading to treatment heterogeneity in this common subgroup of patients. Methods-We utilized the National Cancer Database to perform survival and multivariable analyses of patients with HPV+ OPSCC with one positive lymph node <6 cm and negative surgical margins. Results-We found that 5-year survival is comparable between patients who receive surgery and adjuvant radiation versus surgery alone. In multivariable analyses, we found no significant difference in the hazard-ratio of overall survival after adjusting for various potential confounders. Conclusions-These data suggest that patients with margin-negative HPV+ OPSCC with a single positive lymph node <6 cm have comparable survival with or without adjuvant radiation.

Predictors of overall survival in human papillomavirus-associated oropharyngeal cancer using the National Cancer Data Base

Oral Oncology, 2016

Objectives: This study identifies clinical characteristics associated with HPV-positive oropharynx squamous cell carcinoma (OPSCC) and evaluates predictors of overall survival (OS) in HPV-positive patients undergoing definitive treatment within the National Cancer Data Base (NCDB). Material and methods: The NCDB was queried for patients P18 years old with OPSCC and known HPV status who underwent definitive treatment: surgery, radiation (RT), chemotherapy-RT (CRT), surgery + RT, surgery + CRT (S-CRT). Cox proportional hazards model was used for multivariate analysis (MVA) to evaluate predictors of OS by HPV status. Results: 3952 patients were included: 2454 (62%) were HPV-positive. Median follow up was 23.7 months (range, 1.0-54.5). Unadjusted 2-year OS rates for HPV-positive vs. negative were 93.1% vs. 77.8% (p < 0.001) with an adjusted hazard ratio of 0.44 (95% CI, 0.36-0.53; p < 0.001). MVA identified multimodality treatment including CRT (HR, 0.42; p = 0.024) and S-RT (HR, 0.30; p = 0.024), but not S-CRT (HR, 0.51; p = 0.086), as predictors for improved OS in HPV-positive stage III-IVB disease. Multimodality treatment including S-CRT was associated with longer OS in HPV-negative OPSCC. Nodal stage was poorly associated with OS in HPV-positive cancers. The presence of positive margins and/or extracapsular extension was associated with worse OS in HPV-negative (HR, 2.11; p = 0.008) but not HPV positive OPSCC (HR, 1.61; p = 0.154). Conclusion: The established demographic and clinical features of HPV-positive OPSCC were corroborated in the NCDB. Population analysis suggests that AJCC staging is poorly associated with OS in HPV-positive cancer, and traditional high-risk features may be less impactful. Bimodality therapy appears beneficial in HPV-positive HNSCC.

Patterns of nodal metastasis and prognosis in human papillomavirus-positive oropharyngeal squamous cell carcinoma

2014

Background. The current American Joint Committee on Cancer (AJCC) staging system may not accurately reflect survival in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to develop a system that more precisely predicts survival. Methods. CT scans from 156 patients who underwent chemoradiation for advanced-stage oropharyngeal SCC with >2 years follow-up were reviewed. We modeled patterns of nodal metastasis associated with different survival rates. We defined HPV1 N1 as a single node <6 cm, ipsilaterally, contralaterally, or bilaterally. HPV1 N2 was defined as a single node 6 cm or 2 nodes ipsilaterally/contralaterally or 3 nodes bilaterally. HPV1 N3 was defined as matted nodes. Results. There was no significant difference in disease-specific survival (DSS; p 5 .14) or overall survival (OS; p 5 .16) by AJCC classification. In patients grouped by HPV1 N1, HPV1 N2, and HPV1 N3 nodal classification, significant differences in DSS (100%, 92%, and 55%, respectively; p 5 .0001) and OS (100%, 96%, and 55%, respectively; p 5 .0001) were found. Conclusion. A staging system with reclassification of size, bilaterality, and matted nodes more accurately reflects survival differences in this cohort of patients. Review of the AJCC staging system with these criteria should be considered for HPV-positive oropharyngeal SCC. V

Human papillomavirus is independent prognostic factor on outcome of oropharyngeal squamous cell carcinoma

Tumor Biology, 2013

The primary aim of this study is to assess differences in patients' clinicopathological characteristics based on human papillomavirus (HPV) status and the effect of HPV status on outcome in oropharyngeal squamous cell carcinoma (OSCC). The medical registry of 81 patients who were treated for OSCC was retrospectively analyzed. Factors that are found to be predictive of poor overall survival and event risk by univariate Cox's regression analysis included age greater than 60 years (hazard ratio (

Impact of contralateral lymph nodal involvement and extranodal extension on survival of surgically managed HPV-positive oropharyngeal cancer staged with the AJCC eighth edition

Oral Oncology, 2019

Objectives: Contralateral lymph node (LN) involvement is a prognostic factor in clinical staging of oropharyngeal squamous cell carcinoma (OPSCC), while pathologic nodal staging in the AJCC 8th edition for human papillomavirus-mediated OPSCC (HPV + OPSCC) focuses exclusively on the number of involved LNs (pLN+). This study assessed if the presence of contralateral pLN+ adds prognostic importance to the number of pLN+. Materials and methods: The National Cancer Database was queried for pLN+ HPV + OPSCC treated with surgery with 10 or more LN dissected. Data were evaluated with Cox regression, propensity score matching (PSM), and Kaplan-Meier overall survival (OS) analysis. Results: Of 3407 patients, 152 (4.5%) patients had contralateral pLN+. Subjects with contralateral pLN+ had higher pT/pN stage, more positive margins, extranodal extension (ENE), and lymphovascular invasion (LVI) (all p < 0.05). On univariate analysis, contralateral pLN+ trended toward worse OS (HR 1.58, 95% CI 0.98-2.55, p = 0.061). In the multivariable model (controlling for age, comorbidities, T-stage, N-stage, LN size, ENE, LVI, margin status and adjuvant therapy), LN laterality had no impact on OS (HR 0.87, 95% CI 0.52-1.45, p = 0.520). Further PSM analysis confirmed that contralateral pLN+ is not associated with OS in this population (HR 0.79, 95% CI 0.41-1.53, p = 0.494). Conclusion: This study supports the AJCC 8th edition pathologic staging for HPV + OPSCC by observing that LN laterality is not associated with OS. ENE was associated with inferior OS and should be considered for future staging systems. Further study should be directed at the importance of nodal size in this population.

HPV status and regional metastasis in the prognosis of oral and oropharyngeal cancer

European Archives of Oto-Rhino-Laryngology, 2008

Prognostic factors are important for treatment decisions as they help adapt the therapy on a case-to-case basis. Nodal status, number of positive nodes, and presence of extracapsular spread are considered to be the important prognostic factors in head and neck cancer. Some studies suggest that human papillomavirus (HPV) status also inXuences the outcome of the treatment. This inXuence can be explained by the variation in tendency to develop regional metastases and by variation in the type of neck node involvement. The study objectives were to compare patients with HPV positive and HPV-negative tumors for survival and prevalence and type of regional metastasis, to identify prognostic factors and to test whether HPV presence is an independent factor of survival. The study included 81 patients treated by surgery including neck dissection for oral or oropharyngeal squamous cell cancer. A computerized medical report was completed for each patient. Analysis of the tumor specimen for the HPV DNA presence was done on paraYn-Wxed tissue. HPV DNA detection and typing were performed by PCR with GP5 + / GP6 + BIO primers and reverse line blot hybridization. Overall, 64% (52/81) of tumors were HPV positive with 80% in the tonsillar site. HPV-positive patients had signiWcantly better both overall (73 vs. 35%) (P = 0.0112) and disease-speciWc (79 vs. 45%) (P = 0.0015) survival rates than HPV-negative patients. No signiWcant diVerences were found in the pN classiWcation, in the number of positive nodes and the presence of extracapsular spread in the involved nodes between HPV positive and HPV-negative tumors. Multivariate analysis showed that signiWcant prognostic factors of survival were the presence of HPV in the tumor, extracapsular spread and tumor size. HPV was the most signiWcant prognostic factor in the studied group of patients with oropharyngeal tumors (HR = 0.27, 95%CI 0.12-0.61) and possibly should be considered in treatment decisions.

Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma

Cancer

BACKGROUND: Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV-negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV-driven disease. In p16-negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16-positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16-positive OPSCC. METHODS: In a cohort of 92 patients with p16-positive, lymph node (N)-positive (stage III-IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16-positive/HPV16 DNA-positive, 62 of 92 (67%) were ECE-positive, and 45 of 62 (72.6%) were ECE-positive, p16-positive, and HPV16 DNA-positive. Differences in outcome were assessed using Kaplan-Meier plots and Cox proportional hazard regression (CoxR) for tumor-specific survival and overall survival (OS). RESULTS: The mean numbers of positive lymph nodes in ECE-positive patients (5.0 positive lymph nodes; 95% CI, 3.8-6.4 positive lymph nodes) and ECE-negative patients (2.4 positive lymph nodes; 95% CI, 1.8-2.9 positive lymph nodes) were different (P = .0007). ECE affected OS and tumor-specific survival in p16-positive patients (P = .007 and P = .047, respectively) and in p16-positive/HPV16 DNA-positive patients (P = .013 and P = .026, respectively). Related to the unequal distributions of ECE-positive/HPV16 DNA-negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16-positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17-9.89; P = .025) and even greater impaired OS in those with p16-positive/HPV16 DNA-positive OPSCC (HR, 8.64; 95% CI, 1.12-66.40; P = .038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors. CONCLUSIONS: ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16-positive OPSCC because several lines of evidence demonstrate their impact on survival.

Refining American Joint Committee on Cancer/Union for International Cancer Control TNM Stage and Prognostic Groups for Human Papillomavirus-Related Oropharyngeal Carcinomas

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015

To refine stage and prognostic group for human papillomavirus (HPV) -related nonmetastatic (M0) oropharyngeal cancer (OPC). All patients with nonmetastatic (M0) p16-confirmed OPC treated with radiotherapy with or without chemotherapy from 2000 to 2010 were included. Overall survival (OS) was compared among TNM stages for patients with HPV-related and HPV-unrelated OPC separately. For HPV-related OPC, recursive partitioning analysis (RPA) derived new RPA stages objectively. Cox regression was used to calculate adjusted hazard ratios (AHRs) to derive AHR stages. The performance of survival prediction of RPA stage and AHR stage was assessed against the current seventh edition TNM stages. Prognostic groups were derived by RPA, combining RPA stage and nonanatomic factors. The cohort comprised 573 patients with HPV-related OPC and 237 patients with HPV-unrelated OPC, with a median follow-up of 5.1 years. Lower 5-year OS with higher TNM stage was evident for patients with HPV-unrelated OPC...

Lymph node ratio as a prognostic factor in head and neck cancer patients

Radiation oncology (London, England), 2015

Lymph node status is one prognostic factor in head and neck cancer. The purpose of this study is to investigate the prognostic value of lymph node ratio (LNR) in head and neck cancer patients who received surgery plus postoperative chemoradiotherapy. From May 1991 to December 2012, a total of 117 head and neck cancer patients who received surgery plus postoperative chemoradiotherapy were analyzed. The primary sites were oral cavity (93), oropharynx (13), hypopharynx (6), and larynx (5). All patients had pathologically confirmed squamous cell carcinoma and 63 patients had neck lymph nodes metastasis. LNR was calculated for each patient. The endpoints were overall survival (OS), local failure-free survival (LFFS), and distant metastasis-free survival (DMFS). The median follow up time was 36 months, with a range from 3.4 to 222 months. The 3-year rates of OS, LFFS, and DMFS were 59.7, 70.3, and 81.8 %, respectively. The median value of LNR for lymph nodes positive patients was 0.1. In ...