Significance of Worst Pattern of Invasion-5 in Early-Stage Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: There is an ongoing need to identify pathologic prognosticators in early-stage oral cavity squamous cell carcinoma (OCSCC) to aid selection of patients who may benefit from adjuvant treatment. The objective of this study was to evaluate the prognostic ability of worst pattern of invasion-5 (WPOI-5) defined by the presence of satellite nodules, extratumoural perineural invasion (PNI) and/or extratumoural lymphovascular space invasion (LVI) in low-stage, node negative OCSCC. METHODS: This was a retrospective study of 160 patients with T1/T2N0 tumours staged using TNM7 treated surgically. Histology of the primary tumour was re-reviewed as appropriate to assess for the presence of WPOI-5 parameters. Univariate and multivariate analysis assessing impact of pathological features on survival outcomes was performed. RESULTS: On univariate analysis, WPOI-5 and its 3 constituent components of satellite nodules, extratumoural PNI and extratumoural LVI were all significantly associated with disease-specific survival (DSS) and overall survival (OS). On multivariate analysis, satellite nodules (odds ratio 6.61, 95% CI 2.83-15.44, p < 0.0001) and extratumoural LVI (odds ratio 9.97, 95% CI 2.19-45.35, p = 0.003) were independently associated with OS. Postoperative radiotherapy (odds ratio 0.40, 95% CI 0.19-0.87, p = 0.02) and non-tongue subsite (odds ratio 3.03, 95% CI 1.70-5.39, p = 0.0002) were also significantly associated with OS on multivariate analysis. CONCLUSION: Satellite nodules and extratumoural LVI correlated significantly with survival outcomes in our early-stage OSCC cohort. Further study is required to investigate the benefit of adjuvant treatment in these cases and to ascertain if WPOI-5 parameters including satellite nodules should be mandatory reporting data elements.

Comparison of royal college of pathologists and college of american pathologists definition for positive margins in oral cavity squamous cell carcinoma.

BACKGROUND: Pathological margin assessment is an essential component of surgical management of oral cavity squamous cell carcinoma (OCSCC), however, in many studies, variable definitions of involved margins have been used. The purpose of the present study was to compare the prognostic ability of involved margins according to Royal College of Pathologists (RCPath) and College of American Pathologists (CAP) guidance. METHODS: Retrospective study of 300 patients with previously untreated OCSCC undergoing definitive surgical management. Main specimen margin status was defined according to RCPath guidance and CAP guidance. "Final margin status", incorporated the results of frozen sections and extra tumour bed resections. The prognostic impact of each margin definition was studied using univariate analysis, and in multivariate models including T-stage (AJCC 8th edition), nodal status (pN+), extranodal extension (ENE), and use of adjuvant radiotherapy. RESULTS: Both RCPath and CAP positive margins were associated with local recurrence (LR), disease-specific survival (DSS), and overall survival (OS) on univariate analysis, while final margin status was associated with LR and DSS, but not OS. On multivariate analysis, only CAP positive main specimen margin status was independently associated with LR (odds ratio 2.44, 95% CI 1.37, 4.34), DSS (odds ratio 2.28, 95% CI 1.31, 3.82), and OS (odds ratio 1.59, 95% CI 1.04, 2.42). CONCLUSIONS: Involved main specimen margin as defined by CAP guidance has the advantage of being an independent prognosticator of LR and survival in our cohort.

Cytokeratin 7 and 19 expression in oropharyngeal and oral squamous cell carcinoma.

PURPOSE: The precise etiopathogenesis of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC), and reasons for predilection for crypt epithelium, remain uncertain. The purpose of this study is to investigate the interaction between HPV and specific cytokeratins 7 (CK7) and 19 (CK19) in crypt epithelium. METHODS: This is a retrospective cohort study of patients presenting between 1999 and 2015 at a tertiary referral center. CK7 and CK19 positivity and H Scores were determined by immunohistochemistry. Disease-specific and overall survival rates were analyzed. RESULTS: There were 253 patients presenting with OPSCC (134), squamous cell carcinoma (SCC) of unknown primary site (22), and oral tongue SCC (97). Primary tumor CK7 and CK19 positivity and H Scores were significantly higher in HPV-positive OPSCC than HPV-negative OPSCC and oral tongue SCC. Higher CK19 Scores, but not CK7 Scores, were also seen in regional metastases from HPV-positive OPSCC than other sites. No impact on disease-specific or overall survival was identified on multivariate analysis. CONCLUSION: The increased expression of CK7 and CK19 in HPV-positive OPSCC compared to HPV-negative disease supports the theory for a role for these cytokeratins in the etiopathogenesis of HPV-related OPSCC.

Pre-operative testing for SARS-CoV-2 and outcomes in otolaryngology surgery during the pandemic: A multi-center experience.

INTRODUCTION: Preoperative testing for COVID-19 has become widely established to avoid inadvertent surgery on patients with COVID-19 and prevent hospital outbreaks. METHODS: A prospective cross sectional study was carried out in two university hospitals examining the pre-operative protocols for patients undergoing otolaryngology surgery and the incidence of COVID-19 within 30 days of surgery in patients and the otolaryngologists performing surgery. RESULTS: One hundred and seventy-three patients were recruited. One hundred and twenty-three (71%) patients "cocooned" for 14 days prior to surgery. All completed a questionnaire prior to admission. One hundred and fifty-six patients (90%) had reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swabs, 14 patients (8%) had CT thorax. No cases of COVID-19 were detected among patients followed up at 30 days. Two surgeons developed COVID-19 early during the study period. CONCLUSION: Current pre-operative testing protocols consisting primarily of questionnaires and RT-PCR resulted in zero cases of COVID in this cohort. It is possible that COVID-19 restrictions and high proportion of patients cocooning preoperatively were factors in ensuring a low rate of COVID-19 post-operatively.

Prognostic performance of TNM8 staging rules in oral cavity squamous cell carcinoma.

BACKGROUND: Two major changes to the staging of oral cavity squamous cell carcinoma (OCSCC) were adopted in TNM8: (1) depth of invasion is now used for T staging and (2) extranodal extension for N staging. The aim of this study was to evaluate if TNM8 stratifies OCSCC patients more accurately than TNM7 based on overall survival (OS) statistics and hazard discrimination. METHODS: Retrospective study of 297 patients with OCSCC who underwent surgery at our institution. Clinical and pathological data were previously populated from review of medical charts and histological reports. Slides were re-reviewed for depth of invasion measurements. Patients were staged using both TNM7 and TNM8 with overall survival statistics analysed. RESULTS: Overall 118 patients (39.7%) were upstaged using TNM8. Both TNM7 and TNM8 stage categories were highly significant for OS (all p values < 0.0001). Hazard discrimination analysis showed that TNM7 could only differentiate stage III from stage IV disease with significance (OS p = 0.01). In comparison TNM8 could distinguish between stage II and III disease (OS p = 0.047) and between stage III and IV disease (OS p = 0.004). Subsite analysis suggested that both editions of the staging system perform best for tongue primaries. CONCLUSIONS: Although TNM8 showed improved hazard discrimination in comparison to TNM7, problems with discriminative ability persisted with 8th edition staging criteria. Large scale validation studies will be required to direct future refinement of the staging rules and to establish if the continued use of a single staging system for all oral cavity subsites is appropriate.

Impact of 3 mm margin on risk of recurrence and survival in oral cancer.

INTRODUCTION: While positive surgical margins in oral squamous cell carcinoma (OSCC) is generally considered an adverse prognosticator, the significance of close (≤5 mm) margins is more debatable, and has not been widely adopted as an indicator for radiotherapy. MATERIALS AND METHODS: Retrospective study of 244 patients undergoing primary surgical resection of OSCC. The impact on local control (LC), disease-specific survival (DSS) and overall survival (OS) of margins at 1 mm intervals was studied. RESULTS: 65 patients had involved (<1 mm), 119 close (1-5 mm), and 60 clear (>5 mm) main specimen margins. Involved margins was predictive of DSS (p = 0.04), but not LC (p = 0.20) or OS (p = 0.09). Both the 2 mm and 3 mm margin cut-offs were significantly associated with LC (p = 0.02, and p = 0.01), DSS (p = 0.02, and p = 0.007), and OS (p = 0.03. and p = 0.005). In a 3-tier model, use of 3 mm for demarcation between close and clear yielded good separation between survival curves of clear (≥3 mm), and close (1-<3 mm) or involved (<1 mm). Final margins, determined after incorporation of frozen sections and extra margins taken separately, was significant for LC (p = 0.04), but not for DSS (p = 0.05) or OS (p = 0.17). On multivariate analysis, <3 mm margin, T-classification, nodal status, extranodal spread, and postoperative radiotherapy, were independent predictors of DSS and OS. For LC, only T-classification was significant. CONCLUSION: A 3 mm main specimen margin is significantly associated with survival in OSCC and may be useful for demarcation between close and clear. Further study is required to determine any impact on survival of radiotherapy for patients with <3 mm margins as sole indicator for radiotherapy.

The role of tumour morphology in assigning HPV status in oropharyngeal squamous cell carcinoma.

OBJECTIVES: There is no consensus on the optimal approach to human papilloma virus (HPV) testing in oropharyngeal squamous cell carcinoma (OPSCC). Our objective was to classify OPSCC as HPV positive or negative based on (1) morphology alone, (2) p16 status alone, (3) combined morphology and p16 status with additional HPV testing in discordant cases in keeping with 2012 College of American Pathologists (CAP) guidelines (combined approach), and to evaluate and compare survival outcomes. MATERIALS AND METHODS: Retrospective review of 168 patients, 146 with OPSCC and 22 with cervical SCC of unknown primary site (SCCUP). Morphology was classified as keratinizing or non-keratinizing, p16 immunohistochemistry (IHC) performed and additional HPV DNA PCR testing undertaken in cases in which morphology and p16 status were discordant. Survival statistics were evaluated and compared for the 3 different approaches to classification. RESULTS: On univariate analysis all 3 classification methods significantly predicted for overall survival (OS). Both p16 status and the combined approach also predicted for disease specific survival (DSS), whereas morphology fell just outside significance (p = 0.06). On multivariate analysis only the combined approach retained significance for both OS and DSS, whilst morphology was also significant for DSS. CONCLUSIONS: Our findings confirm that tumour morphology significantly predicts for survival in OPSCC. However, we found combined tumour morphology and p16 IHC, with additional testing for discordant cases to be superior to either morphology or p16 IHC alone. Further study is required to establish the optimal testing method for HPV in OPSCC particularly in low prevalence populations.

Tumour Cell Anaplasia and Multinucleation as Prognosticators in Oropharyngeal Squamous Cell Carcinoma.

Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCC) tend to have good outcomes, however a subset does not share this favourable prognosis. The aim of this paper is to investigate the utility of tumour cell anaplasia and multinucleation as prognostic markers in oropharyngeal squamous cell carcinoma. Retrospective review of 104 patients with OPSCC or squamous cell carcinoma of unknown primary site (SCCUP) who underwent primary resection and/or lymph node dissection. Slides of both primary and nodal metastatic disease were assessed for the presence of anaplasia and multinucleation. 53 patients were HPV-positive. Anaplasia was more frequent in males (p = 0.005), smokers (p = 0.003), and HPV-negative disease (p = 0.04). HPV status and > 10 pack-year smoking history were independent predictors of recurrence-free survival (RFS) and disease-specific survival (DSS). Neither anaplasia, nor multinucleation, at the primary site or in cervical metastases, had any significant impact on RFS or DSS. We did not find either anaplasia or multinucleation to have any significant prognostic impact in OPSCC. However, given the small number of adverse events in the HPV-positive cohort, we may have lacked sufficient power to detect significance in what was the subgroup of primary interest. Our study highlights the challenge of identifying markers of poor prognosis in HPV-positive OPSCC.

Outcomes of transoral laser microsurgery for oropharyngeal squamous cell carcinoma in Ireland and review of the literature on transoral approaches.

BACKGROUND: The optimal treatment for oropharyngeal squamous cell carcinoma (OPSCC) is controversial. There is increasing evidence that, in selected cases, minimally invasive transoral surgery can offer improved functional outcomes, with equivalent oncologic outcomes, compared to chemoradiotherapy. AIMS: We report the outcomes of transoral laser microsurgery (TLM) for treatment of OPSCC at our institution. METHODS: Patients with OPSCC undergoing TLM at the South Infirmary Victoria University Hospital, Cork, between 2010 and 2016, were identified from an institutional database. Human papillomavirus (HPV) status was determined by p16 immunohistochemistry. Survival outcomes were analysed using the Kaplan-Meier method. Complications following surgery and gastrostomy tube dependence were evaluated. RESULTS: The study cohort consisted of 26 patients, with mean age of 56 years (range 29-71). Primary tumours were located in the tonsil (18), base of tongue (4) and other subsites (4). Seventeen cases were p16-positive. Complications included haemorrhage necessitating return to theatre (1) and aspiration pneumonia (1). Four patients underwent tracheostomy, all of whom were successfully decannulated. One patient underwent gastrostomy tube insertion during postoperative radiotherapy. No patient was gastrostomy dependent at latest follow-up. Twenty-two patients received adjuvant treatment, with radiation alone (21) or chemoradiotherapy (2). Mean follow-up was 27 months. Five-year locoregional control was 92% and disease-specific survival was 81%. CONCLUSIONS: In selected patients with OPSCC, TLM offers excellent functional and survival outcomes, and as such offers an alternative approach to chemoradiotherapy as primary treatment. We compare TLM to other transoral approaches and discuss its potential use in the Irish healthcare system.