Treatment Outcomes of Adenoid Cystic Carcinomas of the Head and Neck Region-A Single-Institution Experience.

Malu RafiObjectives This study was undertaken to evaluate the characteristics and treatment outcomes of patients with adenoid cystic carcinomas of the head and neck region treated at a tertiary cancer center in south India. Materials and Methods This was a retrospective study done on patients treated at the institute between 2004 and 2011. Clinicopathological details and treatment outcomes were captured from the treatment records to estimate the treatment outcomes and factors affecting them. Results There were a total of 140 patients with mean age of presentation of 46 years and a median follow-up of 65 months. The most common single site of presentation was the oral cavity. One-hundred eighteen patients (84.3%) underwent primary surgical resection in which 38% had negative surgical margins. Ninety-nine patients were given adjuvant radiotherapy and 18 patients received radical radiotherapy, mostly for surgically inaccessible and inoperable tumors. Median time to recurrence and distant metastasis was 37 and 34 months, respectively. The overall survival and disease-free survival estimate using the Kaplan-Meier method were 92.3 and 71.9%, respectively, at 5 years. Surgical removal of the primary tumor and the nodal stage had the most significant impact on the overall survival outcomes of these patients. Conclusion Surgery remains the most impactful treatment modality in the management of these rare epithelial tumors. The use of adjuvant radiotherapy may help to tackle the issues of perineural spread and inadequate surgical margins in technically difficult sites. Radical radiotherapy also has impressive response rates.

SMARCB1 deficient sinonasal carcinoma: An emerging entity with a diagnostic challenge.

SMARCB1 deficient sinonasal carcinomas are rare neoplasms, classified under sinonasal undifferentiated carcinomas by the fourth edition of the World Health Organization (WHO) classification of head and neck tumors. It is characterized immunohistochemically by loss of SMARCB1(INI1) expression. We are reporting the case of a 63-year-old man who was evaluated for nasal stuffiness of 3 months duration in another hospital where a radiological evaluation showed a polypoidal soft tissue lesion in the right maxillary sinus extending to the right nasal cavity and spheno-ethmoidal sinus. He underwent excision biopsy which was reported as non- keratinizing nasopharyngeal carcinoma. He was referred to our center with residual disease in spheno-ethmoidal recess for which radiotherapy was given. After completion of radiotherapy, the primary site had no residual disease, but while on follow-up he developed left sided neck nodes within 4 months of completion of treatment. Excision of the lesion was done and histopathological and immunohistochemical analysis revealed it to be metastasis from SMARCB1 deficient sinonasal carcinoma and not nasopharyngeal carcinoma as diagnosed from the other center. This case is being reported to highlight the diagnostic challenge associated with this rare entity.

Outcomes of organ preservation treatment in advanced laryngeal carcinoma: A retrospective analysis from a single institution.

Chemoradiation is the standard treatment for patients with locally advanced laryngeal carcinoma with intact cartilage and functional larynx. The aim of this retrospective study was to assess overall survival (OS) and disease-free survival (DFS) of patients with locally advanced (stage III and stage IV) squamous cell carcinoma of the larynx who have been treated with definitive radical radiotherapy (RT) with or without chemotherapy in a tertiary cancer center in India between January 1, 2006 and December 31, 2015. Data were collected using structured proforma. The patients were treated with RT alone, induction chemotherapy (IC) followed by RT, concurrent chemoradiation therapy (CCRT) or IC followed by CCRT. Response assessment was conducted at 3-4 months post-treatment. Patient-, tumor- and treatment-related factors were documented and were associated with DFS and OS. Survival curves were generated using the Kaplan-Meier method and the statistical significance of survival curves was assessed using the log-rank test. Prognostic factors were assessed using the Cox proportional hazards regression model. A total of 630 patients were included in the present study. The most common age group at presentation was 50-70 years (n=477; 75.7%) and 95.4% (n=601) patients were male. The most common stage at presentation was stage III (n=367, 58.1%). The median follow-up period for the entire group of was 59 months (range, 2-175 months). A complete response after treatment was seen in 549 patients (87.1%). Salvage surgery was performed for 11 patients with residual disease. A total of 134 patients (21.3%) had developed locoregional and distant relapses, and salvage surgery was performed for 31 out of 102 patients with locoregional relapse. The 5-year OS was 48.7% and the 5-year DFS was 45.7%. The stage-wise OS rates were 58.9, 34.9 and 30.4% (P=0.001) and the stage-wise DFS rates were 56.3, 32.0 and 21.7 (P=0.001) for stage III, IVa and IVb, respectively. Results from the present study demonstrated the feasibility of delivery of chemoradiation protocols with good results in a developing country.

Epstein-Barr virus dynamics and its prognostic impact on nasopharyngeal cancers in a non-endemic region.

Background: Epstein-Barr virus (EBV) DNA quantification in nasopharyngeal cancer (NPC) is an indicator of the tumour burden, stage and survival. Although EBV dynamics in endemic regions has been extensively studied and reported, the data from non-endemic regions is sparse. This study attempts to investigate the EBV dynamics in NPC patients from a non-endemic region and also to identify the factors impacting the outcomes. Materials and methods: This was a prospective observational study conducted at a tertiary care centre in South India and enrolled patients with non-metastatic, biopsy proven NPC, who were suitable for radical chemo-radiotherapy with or without induction chemotherapy. Two blood samples, one prior to initiation of any anticancer treatment, and second at 6 weeks post treatment, were collected to quantify EBV DNA using real-time quantitative polymerase chain reaction. Antibodies against EBV viral capsid antigen (EBV VCA IgM), EBV Early Antigen (EBV EA IgG) and EBV Nuclear Antigen (EBV EBNA IgG) were also measured in the sample. The impact of EBV dynamics on the outcomes was then analysed. Results: The study included a total of 35 patients. Thirty-three had identifiable EBV DNA (94.3%) and a histological diagnosis of non-keratinising undifferentiated type of squamous cell carcinoma. There was no correlation between the EBV DNA and anti-EBV antibodies. There was a significant association between composite stage and pre-treatment DNA titre (p = 0.030). The mean EBV DNA titre was lower for patients with no clinically demonstrable disease at last follow-up and the reduction in EBV DNA titres was significant (p = 0.020) for those patients who remained disease free. Conclusion: Plasma EBV DNA is an accurate and reliable biomarker for NPC for WHO type 2 and 3 tumours even in non-endemic regions.

Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India✰.

In this article, we highlight the evolution of a multimodal approach in the overall management of squamous cell carcinoma of the head and neck (SCCHN) in India; present advances in technology (newer surgical techniques), novel medical and radiotherapy (RT) approaches; review their roles for an integrated approach for treating SCCHN and discuss the current role of immunotherapy in SCCHN. For locally advanced (LA) SCCHN, the multidisciplinary approach includes surgery followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy. Improved surgical techniques of reconstruction and voice-preservation are being implemented. Advanced forms of high-precision conformal techniques like intensity-modulated radiotherapy are used to deliver highly conformal doses to tumors, sparing the surrounding normal tissue. Compared with RT alone, novel CT regimens and targeted therapeutic agents have the potential to improve locoregional control and survival and reduce treatment-induced toxicities. Several clinical trials have demonstrated efficacy, safety, and quality of life benefits of adding cetuximab to RT regimens in LASCCHN. Studies have also suggested a cetuximab-related laryngeal preservation benefit. At progression, platinum-based CT combined with cetuximab (a monoclonal anti-epidermal growth factor receptor antibody) is the only validated option available as the first-line therapy. Thus, an integrated multidisciplinary approach plays a key role in maximizing patient outcomes, reduction in treatment related morbidities that consequently impact quality of life of survivors.

Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland: Not so indolent a neoplasm?

A 58-year-old female, a known diabetic and hypertensive, presented with left-sided swelling on the anterior aspect of the neck of 1-year duration, which was rapidly increasing in size for the past 6 months. She was on Eltroxin for hypothyroidism for the past 1 year. Computed tomography study of the neck showed a nodule in the left lobe of thyroid which on fine-needle aspiration was suspicious for malignancy. Total thyroidectomy with left posterolateral lymph node dissection was done. Histopathological examination showed sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) of the thyroid gland with lymph node metastasis. SMECE of the thyroid was initially thought to be a low-grade malignancy with indolent clinical behavior. However, our case showed extra thyroidal spread with lymph node metastasis, necessitating adjuvant therapy for our patient. Such aggressive behavior has been noted in few earlier case reports also.

Setup uncertainties and PTV margins at different anatomical levels in intensity modulated radiotherapy for nasopharyngeal cancer.

AIM: To determine the systematic error (∑), random error (σ) and derive PTV margin at different levels of the target volumes in Nasopharyngeal Cancer (NPC). MATERIALS AND METHODS: A retrospective offline review was done for patients who underwent IMRT for NPC from June 2015 to May 2016 at our institution. Alternate day kV images were matched with digitally reconstructed radiographs to know the setup errors. All radiographs were matched at three levels - the clivus, third cervical (C3) and sixth cervical (C6) vertebra. The shifts in positions along the vertical, longitudinal and lateral axes were noted and the ∑ and σ at three levels were calculated. PTV margins were derived using van Herk's formula. RESULTS: Twenty patients and 300 pairs of orthogonal portal films were reviewed. The ∑ for the clivus, C3 and C6 along vertical, longitudinal and lateral directions were 1.6 vs. 1.8 vs. 2 mm; 1.2 vs. 1.4 vs. 1.4 mm and 0.9 vs. 1.6 and 2.3 mm, respectively. Similarly, the random errors were 1.1 vs. 1.4 vs. 1.8 mm; 1.1 vs. 1.2 vs. 1.2 mm and 1.2 vs. 1.3 vs. 1.6 mm. The PTV margin at the clivus was 4.4 mm along the vertical, 4 mm along the longitudinal direction and 3.2 m in the lateral direction. At the C3 level, it was 5.5 mm in the vertical, 5 mm in the lateral direction and 4.4 mm in the longitudinal direction. At the C6 level, it was 6.4 mm in the vertical, 6.9 mm in the lateral direction and 4.4 mm in the longitudinal direction. CONCLUSION: A differential margin along different levels of target may be necessary to adequately cover the target.

Efficacy of Varunadi Ghritha (polyherbal compound) in treated head and neck cancer cases as a biological response modifier.

BACKGROUND: Persistent immune suppression is reported in Head and Neck Cancers (HNC) even after treatment and a higher recurrence rate was observed in patients with poor CD3 count. Loco regional recurrences and second primary tumours are the common forms of failure in head and neck cancers. Several agents have been tried to overcome this problem without much benefit. In Ayurveda, several plant based products have been reported to have anti-tumour and immunomodulatory properties. AIM: To test the role of Varunadi Ghritha, as an immunomodulator in apparently healthy, treated and controlled HNC patients and to evaluate its effectiveness in preventing locoregional relapses and development of second primary tumours. MATERIALS AND METHODS: Total 78 patients of treated head and neck cancers were randomly selected for intervention and control group. Patients in the intervention group (n = 38) received Varunadi Ghritha, 5gms twice daily for one year and followed up to two years. Patients in the control group (n = 40) were followed up at regular intervals. Immune parameters were assessed in the peripheral blood at base line and at the end of administration of the study compound. RESULTS: In the intervention group, mean percentage increase in CD3, CD19 and CD16 positive cells were significantly higher after the administration of the study compound compared to the control group indicating an immunomodulatory effect of the study compound. A non-significant improvement in disease control was observed in patients with advanced stage of disease in the intervention group. CONCLUSION: Administration of Varunadi Ghritha resulted in an increase in T cell counts in patients with treated HNC.

Randomised Phase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck: rationale for future randomised trials in human papilloma virus-negative disease.

BACKGROUND: This randomised Phase II study assessed the activity and safety of concurrent chemoradiotherapy (CRT) and lapatinib followed by maintenance treatment in locally advanced, unresected stage III/IVA/IVB head and neck cancer. PATIENTS AND METHODS: Patients were randomised 1:1 to concurrent CRT and placebo followed by placebo or concurrent CRT and lapatinib followed by lapatinib. Treatment continued until disease progression or study withdrawal. Primary end-point was complete response rate (CRR) by independent review 6 months post-CRT. RESULTS: Sixty-seven patients (median age 56 years; 97% Eastern Cooperative Oncology Group performance status ≤1; 82% stage IV) were recruited. CRT dose intensities were unaffected by lapatinib: median radiation dose 70 Gy (lapatinib, placebo), duration 49 (lapatinib) and 50 days (placebo); median cisplatin dose 260 mg/m(2) (lapatinib) and 280 mg/m(2) (placebo). Lapatinib combined with CRT was well-tolerated. Grade 3/4 toxicities during CRT were balanced between arms, with the exception of an excess of grade 3 diarrhoea (6% versus 0%) and rash (9% versus 3%) and two grade 4 cardiac events in the lapatinib arm. CRR at 6 months post-CRT was 53% with lapatinib versus 36% with placebo in the intent-to-treat population. The progression-free survival (PFS) and overall survival rates at 18 months were 55% versus 41% and 68% versus 57% for the lapatinib and placebo arms, respectively. The difference between study arms was greatest in p16-negative disease (median PFS >20.4 months [lapatinib] versus 10.9 [placebo]). CONCLUSION: Lapatinib combined with CRT is well-tolerated with numeric increases in CRR at 6 months post-CRT and median PFS in p16-negative disease.

Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: a phase II, randomized, double-blind, placebo-controlled study.

BACKGROUND AND PURPOSE: To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN. MATERIALS AND METHODS: In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250mg/day, 500mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2years; secondary endpoints were LDCR at 1year, objective response rate, progression-free survival, overall survival, and safety and tolerability. RESULTS: Gefitinib (250 and 500mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p=0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p=0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy. CONCLUSION: Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone.

In vivo temporal evolution of ALA-induced normalized fluorescence at different anatomical locations of oral cavity: application to improve cancer diagnostic contrast and potential.

BACKGROUND: The focal goal of this study is to identify optimal accumulation periods for ALA-induced PpIX in different healthy anatomical sites of human oral cavity and different types of abnormal mucosa to improve the accuracy of the clinical applications such as photodiagnosis and tissue grading. MATERIALS AND METHODS: Laser-induced fluorescence (LIF) emission spectra, with excitation at 404 nm from a diode laser, were recorded with a miniature fiber-optics spectrometer from 13 anatomical sites of oral mucosa in 15 healthy volunteers and 30 suspicious sites in 15 patients after topical application of 0.4% 5-ALA solution for 15 min. The optimal accumulation time in different anatomical sites of healthy subjects and abnormal tissues were determined by studying the temporal variation in normalized fluorescence intensities (NFI) at 635, 685 and 705 nm. RESULTS AND DISCUSSIONS: In masticatory anatomical locations such as (gingival and hard palate) and in lining mucosa (inner lip, soft palate, floor of mouth, transition to floor of mouth, alveolus and ventral tongue) except vermillion border of lip (VBL) of healthy subjects (designated as group I), it was observed that optimum time for maximum accumulation of PpIX is 90 min. In comparison, for lateral side of tongue (LST) and dorsal side of tongue (DST) tissues (designated as group II), maximum accumulation of PpIX was observed in 150 min of ALA application. For diverse grade lesions of group I mucosa in patients, maximum accumulation of PpIX was observed in 90 min, whereas, in group II mucosa the optimum accumulation time was 150 min as in the case of healthy mucosa. Further, between different grades oral mucosa, maximum variation in NFI take place at these optimal time periods. CONCLUSIONS: The determination of the optimum accumulation time of ALA in oral mucosa based on NFI helps to improve the diagnostic contrast and accuracy of oral cancer diagnosis, and to plan appropriate timing for ensuing PDT.

Diffuse reflection spectroscopy: an alternative to autofluorescence spectroscopy in tongue cancer detection.

Laser-induced autofluorescence (LIAF) and diffuse reflection spectroscopy (DRS) are two emerging noninvasive optical tools that have shown immense potential to detect oral cavity pre-cancer. In a recent study, we have used spectral ratio reference standards (SRRS) of LIAF intensity ratios F500/F635, F500/F685, and F500/F705 for grading of tissues belonging to sites other than dorsal side of tongue (DST), lateral side of tongue (LST), and vermillion border of lip (VBL) that exhibited similar spectral shape for normal and abnormal tissues. This led to dismal diagnostic accuracies, and for the three LIAF-SRRS, normal tissue values were often misclassified as squamous cell carcinoma (SCC), which means that the true negatives were being wrongly identified as true positives. This study examines the applicability of the site-specific diffuse reflection spectral intensity ratio (R545/R575) of the oxygenated hemoglobin bands to classify different DST lesions and compares the results obtained with those obtained using LIAF-SRRS. DRS-SRRS of R545/R575 differentiated benign hyperplastic DST tissues from normal tissue with a sensitivity of 86% and specificity of 80%, which were indistinguishable using LIAF-SRRS. Further, in distinguishing hyperplastic tissues from premalignant dysplastic lesions, DRS-SRRS gave a sensitivity of 90% and a specificity of 86%, as compared to sensitivity of 89% and specificity of 72% shown by the three LIAF-SRRS together. The diagnostic accuracy and statistical adequacy of the two techniques were assessed by receiver operating characteristic curve (ROC-Curve) analysis. Three LIAF ratios gave a low overall ROC area under curve (ROC-AUCs) of 0.521, whereas the DR ratio (R545/R575) has shown an improved accuracy of 0.970 in differentiating different tissue types. While distinguishing hyperplastic from dysplastic tissues, the DR ratio gave a higher discrimination accuracy of 0.9. Based on these findings, it can be concluded that the DRS-SRRS technique by virtue of its low cost and higher diagnostic accuracies could be a viable alternate to LIAF-SRRS for in vivo screening of tongue pre-cancers and grading of different tissue types.

Clinical grading of oral mucosa by curve-fitting of corrected autofluorescence using diffuse reflectance spectra.

BACKGROUND: Laser-induced autofluorescence (LIAF) and diffuse reflectance (DR) were collectively used in this clinical study to improve early oral cancer diagnosis and tissue grading. METHODS: LIAF and DR emission from oral mucosa were recorded on a fiber-optic spectrometer by illumination with a 404-nm diode laser and tungsten halogen lamp in 36 healthy volunteers and 40 lesions of 20 patients. RESULTS: Absorption dips in LIAF spectra at 545 and 575 nm resulting from changes in oxygenated hemoglobin were corrected using DR spectra of the same site. These corrected spectra were curve-fitted using Gaussian spectral functions to determine constituent emission peaks and their relative contribution. The Gaussian peak intensity and area ratios F500/F635 and F500/F685 were found to be useful indicators of tissue transformation. The diagnostic capability of various ratios in differentiating healthy, hyperplastic, dysplastic, and squamous cell carcinomas (SCCs) were examined using discrimination scatterplots. CONCLUSIONS: The LIAF/DR technique, in conjunction with curve-fitting, differentiates different grades of dysplasia and SCC in this clinical trial and proves its potential for early detection of oral cavity cancer and tissue grading.

Discriminant analysis of autofluorescence spectra for classification of oral lesions in vivo.

BACKGROUND AND OBJECTIVES: Low survival rate of individuals with oral cancer emphasize the significance of early detection and treatment. Optical spectroscopic techniques are under various stages of development for diagnosis of epithelial neoplasm. This study evaluates the potential of a multivariate statistical algorithm to classify oral mucosa from autofluorescence spectral features recorded in vivo. STUDY DESIGN/METHODS: Autofluorescence spectra were recorded in a clinical trial from 15 healthy volunteers and 34 patients with diode laser excitation (404 nm) and pre-processed by normalization, mean-scaling and its combination. Linear discriminant analysis (LDA) based on leave-one-out (LOO) method of cross validation was performed on spectral data for tissue characterization. The sensitivity and specificity were determined for different lesion pairs from the scatter plot of discriminant function scores. RESULTS: Autofluorescence spectra of healthy volunteers consists of a broad emission at 500 nm that is characteristic of endogenous fluorophores, whereas in malignant lesions three additional peaks are observed at 635, 685, and 705 nm due to the accumulation of porphyrins in oral lesions. It was observed that classification design based on discriminant function scores obtained by LDA-LOO method was able to differentiate pre-malignant dysplasia from squamous cell carcinoma (SCC), benign hyperplasia from dysplasia and hyperplasia from normal with overall sensitivities of 86%, 78%, and 92%, and specificities of 90%, 100%, and 100%, respectively. CONCLUSIONS: The application of LDA-LOO method on the autofluorescence spectra recorded during a clinical trial in patients was found suitable to discriminate oral mucosal alterations during tissue transformation towards malignancy with improved diagnostic accuracies.

Oxygenated hemoglobin diffuse reflectance ratio for in vivo detection of oral pre-cancer.

Diffuse reflectance (DR) spectroscopy is a simple, low-cost, and noninvasive modality with potential for distinguishing oral precancer. Recently, in an ex vivo study, the DR spectral ratio (R545/R575) of oxygenated hemoglobin bands at 545 and 575 nm was used for grading malignancy. This work presents the results of clinical trials conducted in 29 patients to detect oral precancer using this ratio. We use site-specific normal spectra from a group of 36 healthy volunteers for comparison with those of patients. Toward this, in vivo DR spectra from 14 anatomical sites of the oral cavity of healthy volunteers are recorded on a miniature fiber optic spectrometer with white light excitation. The R545/R575 ratio is lowest for healthy tissues and appears to increase with the grade of malignancy. As compared to scatter plots that use the mean DR ratio from all anatomical sites, those using site-specific data show improved sensitivity and specificity for early diagnosis and grading of oral cancer. In the case of buccal mucosa, using scatter plots of R545/R575 ratio, we obtain a sensitivity of 100% and specificity of 86% for discriminating precancer (dysplasia) from hyperplasia, and a sensitivity of 97% and specificity of 86% for discriminating hyperplasia from normal.

Laser-induced autofluorescence spectral ratio reference standard for early discrimination of oral cancer.

BACKGROUND: Laser-induced autofluorescence (LIAF) is an emerging noninvasive technique in the biomedical field, especially for cancer detection. The goal of the study was to develop a spectral ratio reference standard (SRRS) to discriminate different grades of oral cancer. METHODS: LIAF emission spectra from oral mucosa were recorded in the 420-720 nm spectral range on a miniature fiberoptic spectrometer from 14 anatomical sites of 35 healthy volunteers and 91 sites of 44 patients, with excitation at 404 nm from a diode laser. RESULTS: Histopathologic analysis of biopsy samples showed that oral mucosa of adjoining malignant sites in patients are not usually normal, but showed various degrees of epithelial dysplasia and hyperplasia. Therefore, instead of using LIAF data from apparently normal lesions of patients as control, spectral data values of the oral mucosa of healthy volunteers were used as control. The autofluorescence emission at 500 nm is characteristic of oral mucosa, whereas in malignant lesions a new peak is seen at 685 nm in addition to the previously reported peaks at 635 and 705 nm. Three spectral ratio reference standard (SRRS) scatterplots were created to differentiate the normal mucosa from hyperplasia, hyperplasia from dysplasia, and dysplasia from squamous cell carcinoma (SCC) using the mean fluorescence intensity ratios (F500/F635, F500/705 and F500/F685) measured from 40 sites in 20 patients and 11 sites in 35 healthy volunteers. During blind tests at 21 sites in 17 patients all 3 SRRS plots showed 100% sensitivity and specificity to discriminate hyperplasia from dysplastic and normal tissues, whereas only the F500/F685 SRRS showed the same sensitivity and specificity to differentiate dysplasia from SCC. CONCLUSIONS: An SRRS criteria based on scatterplots of autofluorescence spectral intensity ratios is described to discriminate oral mucosal variations and screen early stages of tissue progression toward malignancy.