P16-positive Oropharyngeal Squamous Cell Research Articles

Clarification of the margin status by the multidisciplinary tumor board following transoral robotic surgery for p16 positive oropharyngeal squamous cell carcinoma

AbstractObjectivesMargin status interpretation following transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC) is challenging. This study aims to assess the discrepancy between status of margins as reported by the pathologist versus as determined by multi‐disciplinary team review (MDTB).MethodsA retrospective study of 57 patients with OPSCC who underwent TORS from January 2010 to December 2016 was conducted. Our primary outcome measure was the discrepancy between the surgical specimen margins as described in the pathology report versus final margin status that was determined after the multi‐disciplinary team discussion. Fisher's exact test was used.ResultsBased on the pathologist‐report, 29 subjects (51%) had positive margins, compared to 2 (4%) after multi‐disciplinary team discussion. Receipt of chemotherapy correlated with final margin status as determined by MDTB, not with initial main specimen margins (p = .02 and p = .08, respectively). With a median follow up of 28.4 months, two subjects (4%) had loco‐regional recurrence.ConclusionFollowing TORS, there was a significant discrepancy between status of margins as reported by the pathologist versus as determined by MDTB review. Chemotherapy was avoided in 93.1% of cases that were originally reported as positive margins by the pathologist with an acceptably low recurrence rate.Level of evidence4.

Early T1-T2 stage p16+oropharyngeal tumours. Role of upfront transoral robotic surgery in de-escalation treatment strategies. A review of the current literature.

Human papillomavirus is responsible of approximately 70% oropharyngeal tumours and is related with more favourable outcomes. It has led to an increasing interest for de-escalation treatment strategies such as Trans Oral Robotic Surgery (TORS). A literature review was performed searching for the role of TORS as de-escalation modality of treatment in patients with p16 positive oropharyngeal squamous cell carcinoma (OPSCC). Special attention was paid to the potential advantage offered by TORS in reducing adjuvant radiation therapy. Six questions were formulated. 67 studies were selected. Several trials analysing the role of upfront TORS to treat early stage p16+OPSCC and the possibility of reducing the adjuvant radiotherapy were founded. A lot of studies based on the experience of single centres show promising results. Nevertheless to date no definitive data can be extrapolated. The continued investigation of this line of de-escalation therapy with randomized prospective clinical trials is needed.

Predictive value of computed tomography in identifying extracapsular spread of cervical lymph node metastases in p16 positive oropharyngeal squamous cell carcinoma.

Extracapsular spread (ECS) of lymph node metastases is associated with poor prognosis and is an indication for adjuvant chemoradiotherapy. Accurately identifying ECS using imaging may allow us to recommend primary chemoradiotherapy to avoid trimodality treatment. We investigated the accuracy of staging CT in diagnosing ECS in P16+oropharyngeal squamous cell carcinoma (OPSCC). Patients with pathologically determined cervical nodal metastases from P16+OPSCC were included. Two blinded radiologists scored images to predict the presence of ECS in comparison to histopathology. Eighty patients with a total of 91 specimens were evaluated. Pathologic ECS was identified in 53.8% of the patients. Sensitivity and specificity of CT for the two observers were 56.5% and 60.9%, and 73.3% and 66.7%, respectively. The presence of perinodal stranding was found to be significantly associated with pathological ECS. Computed tomography displays consistently high specificity, which may be used to rule out the presence of extracapsular spread in cervical nodal metastases of P16+oropharyngeal squamous cell carcinoma.

HPV RNA CISH score identifies two prognostic groups in a p16 positive oropharyngeal squamous cell carcinoma population

HPV-related and HPV-unrelated oropharyngeal squamous cell carcinomas are two distinct entities according to the Union for International Cancer Control, with a better prognosis conferred to HPV-related oropharyngeal squamous cell carcinomas. However, variable clinical outcomes are observed among patients with p16 positive oropharyngeal squamous cell carcinoma, which is a surrogate marker of HPV infection. We aimed to investigate the prognostic value of RNA CISH against E6 and E7 transcripts (HPV RNA CISH) to predict such variability. We retrospectively included 50 histologically confirmed p16 positive oropharyngeal squamous cell carcinomas (p16 positive immunostaining was defined by a strong staining in 70% or more of tumor cells). HPV RNA CISH staining was assessed semi-quantitatively to define two scores: RNA CISH “low” and RNA CISH “high”. Negative HPV RNA CISH cases were scored as RNA CISH “low”. This series contained 29 RNA CISH low cases (58%) and 21 RNA CISH high cases (42%). Clinical and pathologic baseline characteristics were similar between the two groups. RNA CISH high staining was associated with a better overall survival in both univariate and multivariate analyses (p = 0.033 and p = 0.042, respectively). Other recorded parameters had no prognostic value. In conclusion, HPV RNA CISH might be an independent prognostic marker in p16 positive oropharyngeal squamous cell carcinomas and might help guide therapeutics.

378P Outcomes of p16 positive oropharyngeal squamous cell carcinoma treated with radiotherapy – Results from a tertiary care center in South India

378P Outcomes of p16 positive oropharyngeal squamous cell carcinoma treated with radiotherapy – Results from a tertiary care center in South India

Inter- and intra-observer variability in the classification of extracapsular extension in p16 positive oropharyngeal squamous cell carcinoma nodal metastases

Discern inter- and intra-observer variability in the classification of extracapsular extension (ECE) in p16+ oropharyngeal (OP) SCC comparing pathologists' own criteria versus those of a well-defined classification system. Five pathologists reviewed 50 digitally scanned nodal metastasis slides in three Rounds. Round One was by their own criteria as ECE present or absent, and Rounds Two and Three were with a defined ECE system: Grade 0 (no ECE), 0c (no ECE - thick capsule; no infiltration), 1 (ECE - cells beyond capsule), and 2 (soft tissue metastasis - cells in soft tissue without residual node). Round Three assessed intra-observer variability after an 8 month washout period. In Round One, all five agreed on only 48% of cases (n=24). Fleiss's Kappa value was 0.508 (95% CI: 0.357-0.644). For Rounds Two and Three, Grades 0 and 0c and Grades 1 and 2 were separately grouped as ECE absent or present. In Round Two, all five agreed on 68% of cases (n=34). Fleiss' Kappa was 0.635 (95% CI: 0.472-0.783), indicating statistically significantly better agreement. In Round Three, all five agreed on 64% of cases (n=32) giving a Fleiss's Kappa of 0.639. Pathologists agreed with their prior reads in approximately 90% of cases (average n=45.4, range n=42-49), an average intra-observer Cohen's Kappa of 0.8 (range: 0.68-0.95). Inter- and intra-observer variability rates for classification of soft tissue metastasis (ECE2) were substantially worse. There is substantial inter-, and modest intra-, observer variability among head and neck pathologists for ECE in p16+ OPSCC, which is modestly improved by a defined system.

Pre-radiotherapy feeding tube identifies a poor prognostic subset of postoperative p16 positive oropharyngeal carcinoma patients.

BackgroundThis study explores variables associated with poor prognosis in postoperative p16 positive oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing adjuvant radiotherapy or chemoradiotherapy. Specifically, analysis was done related to timing of feeding tube insertion relative to radiotherapy.MethodsFrom 1997–2009, of 376 consecutive patients with OPSCC, 220 received adjuvant IMRT, and 97 were p16 positive and eligible. Of these, 23 had feeding tube placement before IMRT (B-FT), 32 during/after IMRT (DA-FT), and 42 had no feeding tube (NO-FT). Feeding tubes were not placed prophylactically. These three groups were analyzed for differential tumor, patient, treatment, and feeding tube characteristics, as well as differences in overall survival (OS), disease free survival (DFS), and distant metastasis free survival (DMFS).ResultsPre-RT FT insertion was associated with higher tumor size and depth, T (but not N) and overall stage, comorbidities, presence of chemotherapy, and less use of transoral laser microsurgery/transoral bovie. Additionally, time from surgery to IMRT completion was also statistically longer in the B-FT group. The feeding tube was permanent in 52% of patients in the B-FT group versus 16% in the DA-FT group (p = 0.0075). The 5-year OS for the NO-FT, DA-FT, and B-FT groups was 90%, 86%, and 50%, respectively. The 5-year DFS for the NO-FT, DA-FT, and B-FT groups was 87.6%, 83.6%, and 42.7%, respectively. Multivariate analysis showed that for OS and DFS, feeding tube placement timing and smoking history were statistically significant.ConclusionDue to the poor prognosis of early FT insertion, the presence of FTs at time of radiotherapy consultation can be used as an alternate marker to identify a subset of p16 positive OPSCC patients that have a poor prognosis.

Outcomes of P16 positive oropharyngeal squamous cell carcinoma treated with surgery and adjuvant IMRT

Objectives This study compares the outcomes of patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) treated with surgery followed by adjuvant radiotherapy (aRT) or chemoradiotherapy (aCRT).

Abstract A89: Racial disparity in p16 positive oropharyngeal squamous cell carcinoma

Abstract Oropharyngeal squamous cell carcinoma (OPSCC) has become increasingly prominent. Studies have definitively established a causal relationship between HPV and squamous cell carcinoma of the oropharynx. Up to 95% of HPV positive OPSCC patients are also positive for p16 as determined by immunohistochemical (IHC) methods. Previous research has indicated that HPV positive OPSCC patients have a more favorable prognosis. For this reason, p16 status is emerging as an important consideration during risk stratification when predicting OPSCC patient survival. The majority of studies indicating that p16+ OPSCC patient prognosis is improved are based on research designed to represent a general population. This project examines the influence of p16 positivity on patient prognosis in a retrospective cohort population of 120 patients with OPSCC. Furthermore, this project examines whether these findings are present in different racial/ethnic groups, when other variables, such as disease stage, age, gender and smoking history are similar. These results may lead to better disease management and tailoring treatment taking into consideration the HPV status in OPSCC. Methods: A retrospective cohort of patients from our hospitals with OPSCC was studied. A database was formed to organize history and outcomes for each of the patients. Overall survival (OS) was measured based on months of survival from time of diagnosis to death. Censored data was used to consider patients followed for different lengths of time or lost to follow up. 120 patients, on whom p16 data was available were grouped in 60 African-American (AA) and 60 Caucasian (CA). The 2 groups were matched for stage of disease. Kaplan Meier survival curves were produced to compare OS between 60 AA (31 p16+, 29 p16 -) and 60 CA (35 p16+, 25p16-). The Cox Proportional Model was used in a multivariate analysis in comparing these 2 groups to control for gender, age, tobacco use history, stage of disease at diagnosis and the type of treatment received: radiation and chemotherapy. SPSS version 21 was used for final statistical analysis. Results: CA patients, on univariate analysis showed improved overall survival in p16+ individuals (figure A1. p <.0001). A multivariate analysis also indicated statistically significant differences between p16+ and p16- CA and showed improved survival for those that were p16 + (figure B1. p=.004). AA patients did not show improved survival when p16 positive, by univariate analysis (figure C1. p=.612). A multivariate analysis supported these results by demonstrating that there were no significant overall survival differences between p16+ and p16- AA patients (figure D1. p = .645). Conclusions: 1. This study is in concordance with existing data in the literature, showing improved survival for p16 positive patients only in this studied CA group. 2. However, the benefit of improved survival for p16+ OPSCC was unexpectedly lost in AA patients in this studied group and further studies need to be undertaken to better understand the apparently different disease development. 3. When treating patients with OPSCC racial/ethnic factors should be considered, in addition to p16 status. Citation Format: Gabriela M. Oprea-Ilies, Charles Moore, Mylar Joseph Giri, Andrew J. Page, Shruti K. Rereddy, Bhagirath Majmudar, Susan Muller. Racial disparity in p16 positive oropharyngeal squamous cell carcinoma. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr A89. doi:10.1158/1538-7755.DISP13-A89

Outcomes of p16 Positive Oropharyngeal Squamous Cell Carcinoma Treated with Postoperative Adjuvant IMRT +/- Chemotherapy: A Retrospective Analysis

Recent data has shown that for oropharyngeal squamous cell carcinoma (OPSCC), p16 positivity (p16+), a surrogate for HPV, portends a better prognosis. At Washington University, the most frequent approach for OPSCC is minimally invasive transoral laser microsurgery (TLM) with adjuvant radiotherapy (RT) or chemoradiotherapy (CRT). This retrospective review compares outcomes for OPSCC p16+ patients treated with adjuvant RT or CRT.

Is the improved prognosis of p16 positive oropharyngeal squamous cell carcinoma dependent of the treatment modality?

The incidence of human papilloma virus (HPV) induced oropharyngeal squamous cell carcinoma (OPSCC) increases in the western countries. These OPSCC show distinct molecular characteristics and are characterized by an overexpression of p16, considered a surrogate marker for HPV infection. When compared to patients with p16 negative OPSCC, patients with HPV induced p16 positive OPSCC show a significantly better prognosis, which is reported to be caused by increased radiosensitivity. The objective of the present study was to analyze the impact of p16 expression status on the prognosis of OPSCC treated by either radiotherapy (RT) or primary surgery. Results are based upon a tissue microarray (TMA) of 365 head neck squamous cell carcinomas (HNSCC) including 85 OPSCC with clinico-pathological and follow-up data. p16 positivity correlated significantly with oropharyngeal tumor localization (p < 0.001). Patients with p16 positive OPSCC exhibited a significantly better overall survival than those with p16 negative tumors (p = 0.007). In a multivariate analysis, survival benefit of patients with p16 positive OPSCC was independent of clinico-pathological parameters such as cT and cN classification and treatment modality. The improved prognosis of p16 positive OPSCC is found after RT as well as after surgery.