Early Oral Tongue Research Articles

A role for panendoscopy? Second primary tumour in early stage squamous cell carcinoma of the oral tongue.

Panendoscopy is routinely used for the identification of occult second primary tumours in head and neck squamous cell carcinoma. However, its role in low risk subgroups, particularly non-smoking, non-drinking patients and patients presenting with early stage oral cavity lesions, is debatable. The records of 112 patients with T₁ or T₂ oral tongue squamous cell carcinoma were retrospectively reviewed. Demographic, disease characteristics and survival data were collected. Average follow-up duration was 71.7 months (range, 3.6-238.3 months). Thirty-five patients died within this period. Thirteen second primary events were identified in 11 patients, with all but 2 tumours in the oral cavity or oropharynx. There was a single synchronous primary - a lung adenocarcinoma; all other events were metachronous. No non-smoking, non-drinking patients re-presented with a second primary tumour; tobacco and alcohol use are clearly risk factors for development of a second primary tumour. The role of panendoscopy for identifying synchronous primary tumours in patients with early stage oral tongue squamous cell carcinoma should be re-evaluated, particularly in non-smoking, non-drinking patients who are at low risk of second primary development. Close follow up with regular clinical examination including flexible fibre-optic endoscopy may be sufficient in this subgroup.

Predictors of recurrence in early stage oral tongue squamous cell carcinoma

Introduction: Many histopathological parameters in oral tongue squamous cell carcinoma (OTSCC) have been identified as predictive factors. Certain tumor-related factors increase the risk of nodal metastasis, and many pathological factors affect survival. Objective: The objective of this study is to identify that tumor-related histopathological prognostic factors that can predict recurrence and potentially influence the decision for adjuvant radiotherapy in early stage OTSCC. Materials and Methods: A total of 51 patients who underwent surgery for early stage OTSCC (stage I, II) from 2007 to 2013 were selected. Demographic and clinical details were retrieved. Histopathological reports were reviewed for the following parameters-Margin status (close <5 mm, positive - Invasive squamous cell carcinoma [SCC], carcinoma in situ, marked dysplasia), microscopic depth of invasion, skeletal muscle infiltration (SMI), tumor differentiation, perineural invasion, lymphovascular invasion. Overall survival and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. Predictors of recurrence were identified using Univariate analysis. Results: Median follow-up was 22 months (range, 5-89 months), the overall survival and RFS were 88% and 81% respectively. The recurrence rate was 19.5% during this time period. The only significant predictor of recurrence in pathologically early stage OTSCC was SMI (P = 0.003) on univariate analysis. Eighty-seven percentage of the recurrences in our study occurred within the 1 st year, with a disease specific mortality rate of 12.5%. Conclusion: In early stage OTSCC, Failure occurred predominantly in patients who had SMI.

A simple novel prognostic model for early stage oral tongue cancer

The prognostication of patient outcome is one of the greatest challenges in the management of early stage oral tongue squamous cell carcinoma (OTSCC). This study introduces a simple histopathological model for the prognostication of survival in patients with early OTSCC. A total of 311 cases (from Finland and Brazil) with clinically evaluated early stage OTSCC (cT1–T2cN0cM0) were included in this multicentre retrospective study. Tumour budding (B) and depth of invasion (D) were scored on haematoxylin–eosin-stained cancer slides. The cut-off point for tumour budding was set at 5 buds (low <5; high ≥5) and for depth of invasion at 4mm (low <4mm; high ≥4mm). The scores of B and D were combined into one model: the BD predictive model. On multivariate analysis, a high risk score (BD score 2) correlated significantly with loco-regional recurrence (P=0.033) and death due to OTSCC (P<0.001) in early stage OTSCC. The new BD model is a promising prognostic tool to identify those patients with aggressive cases of early stage OTSCC who might benefit from multimodality treatment.

Risk stratification of early stage oral tongue cancers based on HPV status and p16 immunoexpression.

Recent epidemiological data have implicated human papilloma virus (HPV) infection in the pathogenesis of head and neck cancers, especially oropharyngeal cancers. Although, HPV has been detected in varied amounts in persons with oral dysplasia, leukoplakias and malignancies, its involvement in oral tongue carcinogenesis remains ambiguous. HPV DNA prevalence was assessed by PCR with formalin fixed paraffin embedded sections (n=167) of oral tongue squamous cell carcinoma patients and the physical status of the HPV16 DNA was assessed by qPCR. Immunohistochemistry was conducted for p16 evaluation. We found the HPV prevalence in tongue cancers to be 51.2%, HPV 16 being present in 85.2% of the positive cases. A notable finding was a very poor concordance between HPV 16 DNA and p16 IHC findings (kappa<0.2). Further molecular classification of patients based on HPV16 DNA prevalence and p16 overexpression showed that patients with tumours showing p16 overexpression had increased hazard of death (HR=2.395; p=0.005) and disease recurrence (HR=2.581; p=0.002) irrespective of their HPV 16 DNA status. Our study has brought out several key facets which can potentially redefine our understanding of tongue cancer tumorigenesis. It has emphatically shown p16 overexpression to be a single important prognostic variable in defining a high risk group and depicting a poorer prognosis, thus highlighting the need for its routine assessment in tongue cancers. Another significant finding was a very poor concordance between p16 expression and HPV infection suggesting that p16 expression should possibly not be used as a surrogate marker for HPV infection in tongue cancers. Interestingly, the prognostic significance of p16 overexpression is different from that reported in oropharyngeal cancers. The mechanism of HPV independent p16 over expression in oral tongue cancers is possibly a distinct entity and needs to be further studied.

Abstract 2867: EGFR expression in T1/T2 oral tongue and floor of the mouth carcinoma

Abstract Epidermal growth factor receptor (EGFR) is a molecular maker that regulates the cell growth and plays an important role in tumor proliferation, invasion and metastasis formation. Objective: In this study we examined the association of immunohistochemical expression of EGFR with clinicopathological parameters, lymph node metastasis, regional recurrence and survival in selected cases of early squamous cell carcinoma (SCC) of the oral tongue and floor of the mouth. Methods: Patients with early stage SCC of oral tongue and floor of the mouth were treated surgically at a single institution from 1980 to 2010. Specimens from 139 patients were analyzed for EGFR expression using monoclonal antibody. Results: This study included 139 patients, 96 men (69%), with ages ranging from 21 to 85 years old (mean, 58 years). The tumor site was the tongue in 105 cases (75.5%) and the floor of the mouth in 34 (24.5%). With regard to pathological T-stage, 69 cases were pT1 (52.7%) and 62 were pT2 (47.3%). EGFR was overexpressed in 18 cases (13%) and was significantly associated with pT (p=0.017), thickness greater than 4mm (p=0.017), muscular invasion (p=0.014), desmoplastic reaction (p=0.021), inflammatory infiltrate (p=0.029), lymphatic embolization (p=0.016), mode of invasion (p=0.027) and perineural invasion (p=0.007). The overexpression of EGFR was also associated with lymph node metastasis (p=0.038) and regional recurrence (p=0.014). The cancer-specific survival in 5 years decreased from 90% in the group without EGFR expression to 75.3% in the EGFR overexpression group (p=0.019). Conclusion: The EGFR overexpression was associated with more aggressive pathological features, lymph node metastasis and regional recurrence in patients with early oral tongue and floor of the mouth squamous cell carcinoma. Citation Format: Natalie Kelner, Clovis Antonio Lopes Pinto, Luiz Paulo Kowalski, Claudia Malheiros Coutinho-Camillo. EGFR expression in T1/T2 oral tongue and floor of the mouth carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2867. doi:10.1158/1538-7445.AM2014-2867

A novel tumor: Specimen index for assessing adequacy of resection in early stage oral tongue cancer

Surgical margin status frequently affects decisions regarding adjuvant treatment; however, reporting and interpretation of surgical margins is subject to considerable subjectivity because of many factors including the adequacy of resection. We developed a novel measure of the adequacy of surgical resection, the tumor: specimen index (TSI), and tested its utility at predicting clinical outcomes in a retrospective cohort study. An institutional database was queried to identify previously untreated patients with T1 and T2 oral tongue cancer who underwent surgery during 1985-2009 (n=433). The TSI, a geometric mean representing the percentage of the surgical specimen that is occupied by the tumor in average single dimension, was calculated from the largest measured lengths, widths, and heights of the tumor in relation to the entire surgical specimen. Multivariate analyses of locoregional recurrence-free probability (LRRFP) and disease-specific survival (DSS) were performed with commonly accepted prognosticators in addition to TSI and surgical margins status. The mean TSI was 41 (range 11-90; SD 14). Surgical margin status was associated with TSI; margins were negative in 84% of patients with TSI<45 and in 63% of patients with TSI⩾45 (p<0.001). TSI⩾45 was associated with worse LRRFP (57% vs. 76%, p<0.001) and worse DSS (68% vs. 85%, p<0.001). In a multivariate analysis that did not include TSI, surgical margin status independently predicted LRRFP (p=0.014) but not DSS. When TSI was included, only TSI, and not surgical margin status, was an independent predictor of both LRRFP (p=0.002) and DSS (p=0.011). The tumor: specimen index is an easily-calculated metric for estimating the adequacy of 3-dimensional resection in T1 and T2 oral tongue cancer that independently predicts oncologic outcomes.

A prospective study of prognostic factors for recurrence in early oral tongue cancer.

Tongue cancer is one of the common cancers in head and neck region. Cervical node metastasis is the strongest poor prognostic factor. Other prognostic factors were also said to be of significance. Our aim was to find out the significant prognostic factors of tumor aggressiveness in Indian perspective. Sixty cases of early cancer of oral tongue with clinically non palpable neck nodes were managed by upfront surgery. Surgeries performed for the primary tumor were 'wide excision' or 'hemiglossectomy' along with neck dissection. Patients were then given post-operative radiotherapy according to standard guidelines. They were analyzed using a detailed proforma. Three patients were lost to follow-up rest all patients were followed. Recurrence was seen in 11 out of 60 patients (18.3%), in an average follow-up period of about 28 months. Among those who recurred, one patient had both nodal and local recurrence, 2 patients had nodal only (regional) recurrence and rest 8 patients had local recurrence. The prognostic factors that significantly affected the recurrence were endo-phytic disease, depth of invasion, lymphatic invasion, muscle invasion, healthy margin and adjuvant radiotherapy. The risk factors for recurrence in early lesions of oral tongue are - Cervical nodal metastasis, Lymphatic permeation, Depth of disease - 6 mm or more, poorly differentiated tumor, Endophytic (infiltrative) disease, Young age at presentation and Muscle invasion. In early tongue lesions, that are node negative, selective node dissection (SND) including level 1, 2, 3 and 4, is a viable option for neck to decrease the morbidity of MND.

Patterns of recurrence in early stage (I–II) squamous cell carcinoma of the oral tongue

Background and objectives: The most frequent reported cause of treatment failure in early oral tongue cancer is regional recurrence. We analyzed our data from the recent two decades to review patterns of recurrence in our patient cohort.

Early Stage Oral Tongue Cancer among Non-Tobacco Users - An Increasing Trend Observed in a South Indian Patient Population Presenting at a Single Centre

Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer diagnosed within the oral cavity worldwide. Many studies in India report OTSCC ranking among the top two most common subsites within the oral cavity. India is often labeled the oral cancer capital of the world. The incidence of tongue cancers in the population-based cancer registry (PBCR) of Chennai is showing an increasing trend. A majority of the oral cavity cancers (85%) in our cancer center present in advanced stages (III and IV). In contrast, early tongue cancers (stages I and II) constitute nearly 45% of all OTSCCs. The aim of this study was to analyze the clinical profile and epidemiological trends in our early stage tongue cancer patients with an emphasis on tobacco and alcohol habits. This retrospective analysis was based on a prospectively collected database of 458 consecutive early stage OTSCC in-patients at a tertiary care oncology centre in Chennai between 1995 and 2008. Our study suggests that the earlier trends have clearly changed whereby nearly half of our patients are now never-tobacco users. The findings of the study indicate that a majority of the patients were never alcohol users (86.4%) and nearly half of them were never tobacco users (49.3%), and they had the best survival outcomes. This increasing trend of OTSCC among non-tobacco users is in contrast to our earlier experience of tongue cancer more than five decades ago.The median age of patients in our study was 53.3 years; the male to female ratio was approximately 2:1. The median follow up for the 458 patients was 53 months. Our study importantly as well as interestingly shows a conspicuous absence of association with the traditional risk factors, tobacco and alcohol.

Depth of invasion, tumor budding, and worst pattern of invasion: Prognostic indicators in early‐stage oral tongue cancer

BackgroundOral (mobile) tongue squamous cell carcinoma (SCC) is characterized by a highly variable prognosis in early-stage disease (T1/T2 N0M0). The ability to classify early oral tongue SCCs into low-risk and high-risk categories would represent a major advancement in their management.MethodsDepth of invasion, tumor budding, histologic risk-assessment score (HRS), and cancer-associated fibroblast (CAF) density were studied in 233 cases of T1/T2 N0M0 oral tongue SCC managed in 5 university hospitals in Finland.ResultsTumor budding (≥5 clusters at the invasive front of the tumor) and depth of invasion (≥4 mm) were associated with poor prognosis in patients with early oral tongue SCC (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.17–3.55; HR, 2.55; 95% CI, 1.25–5.20, respectively) after multivariate analysis. The HRS and CAF density did not predict survival. However, high-risk worst pattern of invasion (WPOI), a component of HRS, was also an independent prognostic factor (HR, 4.47; 95% CI, 1.59–12.51).ConclusionAnalyzing the depth of invasion, tumor budding, and/or WPOI in prognostication and treatment planning of T1/T2 N0M0 oral tongue SCC is recommended.

Application value of sentinel node biopsy in early stage oral tongue cancer with clinically negative neck

To evaluate the liability of sentinel node biopsy in the treatment of early stage oral tongue carcinoma with clinically negative neck. Eighteen patients with T1 or T2 oral tongue carcinoma were enrolled in the prospective study. Preoperative lymphoscintigraphy and intra-operative hand-held gamma probe techniques were used to detect the sentinel lymph nodes. The sentinel lymph node biopsies were sent to frozen section pathology and the results were compared with specimen of routine selective neck dissection (I ∼ III or I ∼ IV). The accuracy of cervical metastasis prediction was compared between sentinel node biopsy and tumor thickness. Sentinel lymph nodes were identified in all 18 cases. The numbers of sentinel lymph nodes of level Ib, IIa and III were 6, 22 and 2, respectively. In this series, positive sentinel lymph nodes were revealed in 4 cases, which were also positive in the postoperative routine histology.In other cases, both sentinel lymph nodes and routine histology were negative. Both the sensitivity and specificity were 100%. Sentinel lymph node biopsy obviously improved the specificity of predicting cervical metastasis comparing with the tumor thickness. (100% vs. 36.4%). Sentinel node biopsy is effective and reliable in the treatment of early stage oral tongue cancer, and deserves clinical application.

Relationships between Tumor Volume and Lymphatic Metastasis and Prognosis in Early Oral Tongue Cancer

ObjectivesAlthough T stage is an important prognostic tool for oral tongue cancer, it fails to define the depth of invasion and true three-dimensional volume of primary tumors. The purpose of this paper is to determine the relations between tumor volume and lymph node metastasis and survival in early oral tongue cancer.MethodsForty-seven patients with T1-2 tongue cancer were included. Tumor volumes were measured by the computerized segmentation of T2-weighted magnetic resonance imaging.ResultsThe overall average tumor volume was 27.7 cm3 (range, 1.4 to 60.1 cm3). A significant positive correlation was found between tumor volume and pathological T stage, depth of invasion, and cervical lymph node metastasis (P<0.001, P<0.001, and P=0.002, respectively). When the tumor volume exceeded 20 cm3, the cervical metastasis rate increased to 69.2%. The overall 5-year disease specific survival rate was 80%. There was a statistically significant association between large tumor volume (≥20 cm3) and the 5-year disease-specific survival (P=0.046).ConclusionTumor volume larger than 20 cm3 was associated with greater risk cervical lymph node metastasis and poor 5-year disease-specific survival rate in early oral tongue cancer patients.

Long‐term regional control and survival in patients with “low‐risk,” early stage oral tongue cancer managed by partial glossectomy and neck dissection without postoperative radiation

The objectives of this study were to determine the incidence of locoregional failure in patients with low-risk, early stage oral tongue squamous cell cancer (OTSCC) who undergo partial glossectomy and ipsilateral elective neck dissection without receiving postoperative radiation. A combined database of patients with OTSCC who received treatment at Memorial Sloan-Kettering Cancer Center and Princess Margaret Cancer Center from 1985 to 2005 was established. In total, 164 patients with pathologic T1-T2N0 OTSCC who underwent partial glossectomy and ipsilateral elective neck dissection without postoperative radiation were identified. Patient-related, tumor-related, and treatment-related characteristics were recorded. Local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were calculated by the Kaplan-Meier method. Predictors of outcome were analyzed by univariate and multivariate analysis. At a median follow-up of 66 months (range 1-171 months), the 5-year rates of local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were 89%, 79.9%, and 85.6%, respectively. Regional recurrence was ipsilateral in 61% of patients and contralateral in 39% of patients. The regional recurrence rate was 5.7% for tumors <4 mm and 24% for tumors ≥ 4 mm. Multivariate analysis indicated that tumor thickness was the only independent predictor of neck failure (regional recurrence-free survival, 94% vs 72% [P = .02] for tumors <4 mm vs ≥ 4 mm, respectively). Patients who developed recurrence in the neck had a significantly poorer disease-specific survival compared with those who did not (33% vs 97%; P < .0001). Patients with low-risk, pathologic T1-T2N0 OTSCC had a greater than expected rate of neck failure, with contralateral recurrence accounting for close to 40% of recurrences. Failure occurred predominantly in patients who had primary tumors that were ≥ 4 mm thick.

Neck Dissection for T1 Oral Tongue SCCA: The UCLA Experience

Objective: The study was carried out in order to 1) evaluate features that could identify patients having increased risks of regional recurrences, and 2) examine the prognostic and therapeutic implications of elective neck dissection among patients who presented with early-stage oral tongue squamous cell carcinoma with clinically negative neck (T1cN0). Method: A retrospective chart review of oral tongue cancer at a single tertiary institution identified 123 patients with T1cN0 oral tongue squamous cell carcinoma who underwent surgical tumor extirpation with/without adjuvant radiation treatment and/or chemotherapy from 1990 through 2009. This database was used to identify characteristics that are associated with occult lymph node metastases and measurement of patient outcomes. Results: Eighty-nine patients underwent elective neck dissection, of which 20 patient specimens (22%) were found to harbor occult metastatic disease. However, no significant differences were noted in the frequency of regional recurrence according to gender, age, tumor size, the presence of perineural invasion, or occult metastatic disease ( P = .70, .29, .54, .30, and .47, respectively). In addition, patients who underwent elective neck dissection experienced lower rate of regional recurrence, although this did not achieve a statistically significant level ( P = .52). Conclusion: Clinical observation of the clinically negative neck is justifiable for early stage T1 oral tongue squamous cell carcinoma. Elective cervical lymphadenectomy offers no benefit in preventing regional recurrence when compared to clinical observation. Furthermore, neither patient factors nor intrinsic tumor features demonstrated any prognostic significance in the setting of early stage T1 oral tongue carcinoma.

Trans-oral robotic submandibular gland removal.

Submandibular gland excision is traditionally performed via a trans-cervical approach. While generally regarded as a relatively simple surgical procedure, several complications are possible, including injury to the marginal mandibular branch of the facial nerve, lingual nerve, hypoglossal nerve, facial artery and a visible unsightly neck scar or keloid. The trans-oral route has the ability to eliminate a cervical scar and decrease risk of injury to several structures. Coincident with the development of the trans-oral approach, robotic surgery has been gaining popularity in the operative management of early oral cavity, tonsil, and tongue base malignancies. A 51-year-old female presented to our institution with a 15-year history of recurrent left submandibular gland sialoadenitis. She previously underwent a rhytidectomy with cervicoplasty and was interested in a trans-oral approach to avoid a neck incision. Here we present a novel application of the da Vinci Surgical Robot for trans-oral removal of the submandibular gland.

Dose reduction trial from 60 Gy in 10 fractions to 54 Gy in 9 fractions schedule in high-dose-rate interstitial brachytherapy for early oral tongue cancer

To compare the effects of 60 Gy/10 fractions (twice a day) with those of 54 Gy/9 fractions in high-dose-rate interstitial brachytherapy (HDR-ISBT) for early tongue cancer, we performed a matched-pair analysis of patients with early tongue cancer (T1-2N0M0), who were treated with 60 or 54 Gy of radiation between 1996 and 2004. Seventeen patients treated with 54 Gy and 34 matched-pair patients treated with 60 Gy were extracted and analyzed. Local recurrence occurred in two patients in the 54-Gy arm and five patients in the 60-Gy arm. The 2-year local control rates were 88% for both the 54-Gy arm and 60-Gy arm (not significant). The 2-year overall survival rates were 88% in the 60-Gy arm and 82% in the 54-Gy arm. Two-year actuarial complication-free rates were 91% in the 60-Gy arm and 83% in the 54-Gy arm (not significant), respectively. There was no significant association between the total dose and local control rate and late complications. The outcome of 54 Gy/ 9 fractions was similar to that of 60 Gy/ 10 fractions in patients with early tongue cancer.

Are wider surgical margins needed for early oral tongue cancer?

Traditionally, a 1-cm surgical resection margin is used for early oral tongue tumours. All tumour stage one (n = 65) and stage two (n = 13) oral tongue cancers treated between January 1999 and January 2009 were followed for a median of 38 months (minimum 12 months). The sites of close and involved margins were histologically reviewed. Involved and close margins occurred in 14 and 55 per cent of cases, respectively. The number of involved vs clear or close margins was equivalent in tumour stage one (90 vs 82 per cent), node-negative (100 vs 84 per cent) and perineural or lymphovascular invasion (20 vs 21 per cent) cases. Close or involved margins were similarly likely to be posterior (59 per cent) as anterior (41 per cent, p = 0.22), lateral (57 per cent) as medial (43 per cent, p = 0.34), and mucosal (59 per cent) as deep (41 per cent, p = 0.22). Local recurrence occurred in 28 per cent of cases at a median of 12 months, and was more likely in cases with involved (50 per cent) than clear or close margins (25 per cent, p = 0.10). Disease-free survival was worse in involved margins cases (p = 0.002). Involved margins are common in early tongue tumours, and are associated with increased local recurrence and worse survival. Close or involved margins occur in all directions and all tumour types. A wider margin may be justified.

Robot-Assisted Selective Neck Dissection via Modified Face-lift Approach for Early Oral Tongue Cancer: A Video Demonstration

Robot-Assisted Selective Neck Dissection via Modified Face-lift Approach for Early Oral Tongue Cancer: A Video Demonstration

Predictive factors for regional metastases in oral tongue squamous cell carcinoma

The process of deciding to treat or not to treat the clinically N0 neck in early oral tongue carcinoma whether surgically or with radiotherapy remains difficult and open to discussion. This is due to the minority of patients who will have occult nodal metastases and the reduced outcome for those patients whose neck disease is not treated primarily. Studies which have looked at factors which may predict for nodal metastases both at the histological and immunohistochemical level and therefore help with this decision making process are reviewed.

Long Term Regional Control and Survival in Patients with “Low Risk” Early Stage Oral Tongue Cancer Managed by Partial Glossectomy and Neck Dissection without Postoperative Radiation: The Importance of Depth of Invasion

Long Term Regional Control and Survival in Patients with “Low Risk” Early Stage Oral Tongue Cancer Managed by Partial Glossectomy and Neck Dissection without Postoperative Radiation: The Importance of Depth of Invasion