Oral Cancer Preven,on and Early Diagnosis

Transcription

1 Oral Cancer Preven,on and Early Diagnosis Prof. Surendra S. Shastri MD Technical Advisor IAEA impact Mission Ex Chair, Department of Preven,ve Oncology Head, WHO Collabora,ng Centre For Cancer Preven,on, Screening and Early Detec,on Tata Memorial Centre, Mumbai, India

2 DISEASE BURDEN q Cancer of the head and neck (H&N cancer), including all oral, laryngeal and pharyngeal sites, is the sixth most common cancer, accoun,ng for about new cases annually ( from less developed countries) q About 40% of head and neck malignancies are known to be squamous cell carcinomas arising in the oral cavity q Oral cancer is largely related to lifestyle, with major risk factors being tobacco and alcohol misuse q Smokeless tobacco has been strongly linked to oral cancer

3 DISEASE BURDEN q Five-year survival of oral cancer varies from 81% for pa,ents with localized disease to 42% for those with regional disease and to 17% if distant metastases are present q Generally with late-stage diagnosis, fewer than 50% of pa,ents with oral and pharyngeal cancers survive more than 5 years q This rate has remained disappoin,ngly low and rela,vely constant during the last few decades q Treatment of oral cancer o`en produces dysfunc,on and distor,ons in speech, mas,ca,on and swallowing, and dental health q It can also affect the pa,ent's ability to interact socially, hence it is the most debilita,ng and disfiguring of all cancers

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5 PREVENTION and EARLY DIAGNOSIS Causal Associa+ons q Tobacco q Alcohol q HPV Primary Preven+on q Educa,onal q Regulatory Secondary Preven+on q Cessa,on q Screening

6 CLINICAL RELEVANCE OF SCREENING q Oral squamous cell carcinomas (OSCCs) are preceded by visible changes in the oral mucosa, usually leukoplakia and erythroplakia q Other inflammatory disorders e.g. lichen planus, submucous fibrosis are known to be associated with an increased risk of developing OSCC

7 CLINICAL RELEVANCE OF SCREENING q Iden,fica,on and monitoring of these poten,ally malignant lesions and condi,ons allows us to detect and treat early intraepithelial stages of oral carcinogenesis e.g. mild/ moderate/ severe dysplasia and carcinoma in situ, which generally precede the development of invasive OSCC q The prognos,c value of early diagnosis and treatment of these early intra-epithelial stages of oral carcinogenesis are very significant due to good survival rates of early OSCC

8 CLINICAL RELEVANCE OF SCREENING q Aided visual oral examina,on with normal (incandescent) light, a variety of commercial diagnos,c aids and adjunc,ve techniques are available q These aids are supposed to assist in the detec,on of early cancerous mucosal changes that can be occult to visual inspec,on and/or to assess the biologic poten,al of clinically abnormal mucosal lesions q However, as yet, we have very liile evidence to support the effec,veness of these adjuncts

9 SCREENING AIDS Brush biopsy q The oral brush biopsy (OralCDx Brush Test system) is a method of collec,ng a transepithelial sample of cells from a mucosal lesion with representa,on of the superficial, intermediate and parabasal/basal layers of the epithelium q OralCDx's cytologic test is adver,sed as highly sensi,ve and specific in detec,ng dysplas,c changes in high-risk mucosal lesions q Inconsistencies and poten,al biases have been noted in most of the studies that have looked at the sensi,vity/ specificity of the test

10 SCREENING AIDS Toluidine blue staining q Toluidine blue (TB)/ tolonium chloride is a vital dye that stains nucleic acids and hence used as an aid to iden,fy clinically occult mucosal abnormali,es, par,cularly poten,ally malignant lesions prior to excision q Several studies have been conducted on the efficacy of TB screening, however a majority of them are seen to have significant limita,ons

11 SCREENING AIDS Chemiluminescence q Chemiluminescent blue/white light has been used for oral screening q ViziLite involves the use of an oral rinse with a 1% ace,c acid solu,on for 1 minute followed by the examina,on of the oral mucosa under diffuse chemiluminescent blue/white light (wavelength of 490 to 510 nm) q Ace,c acid removes the glycoprotein barrier and slightly desiccates the oral mucosa, the abnormal cells of the mucosa then absorb and reflect the blue/white light in a different way compared to normal cells. Normal mucosa appears blue, whereas abnormal mucosal areas reflect the light (due to higher nuclear/cytoplasmic ra,o of epithelial cells) and appear more aceto-white, with brighter, sharper and more dis,nct margins

12 SCREENING AIDS Chemiluminescence q Several studies have been conducted with the Vizilite system to demonstrate its efficacy in iden,fying mucosal abnormali,es, however, no study has clearly demonstrated the efficacy of chemiluminescence in differen,a,ng dysplasia/ carcinoma from benign lesions q Modified version of ViziLite includes TB (MicroLux DL)

13 SCREENING AIDS Tissue Fluorescence Imaging q Tissue autofluorescence has been used in the screening and diagnosis of precancers and early cancer of the lung, uterine cervix, skin and oral cavity q Changes in the structure e.g. hyperkeratosis, hyperchroma,n and increased cellular/ nuclear pleomorphism, and metabolism e.g. concentra,on of flavin adenine dinucleo,de [FAD] and nico,namide adenine dinucleo,de [NADH] of the epithelium, as well as changes of the sub-epithelial stroma e.g. composi,on of collagen matrix and elas,n, alter their interac,on with light

14 SCREENING AIDS Tissue Fluorescence Imaging q These changes alter the distribu,on of,ssue fluorophores and thereby the way they emit fluorescence a`er s,mula,on with intense blue excita,on light (400 to 460 nm), a process defined as autoflorescence q The normal oral mucosa emits a pale green autofluorescence when viewed through the instrument (VELscope), whilst the abnormal,ssue exhibits decreased autofluorescence and appears darker as compared to the surrounding healthy,ssue

15 SCREENING AIDS Tissue Fluorescence Imaging q With histology as the gold standard, VELscope demonstrated high sensi,vity and specificity in iden,fying areas of dysplasia and cancers that extended beyond clinically evident tumors, par,cularly in assessing lesion margins q However, these results are from case series and case reports rather than clinical trials, and no published studies have assessed the VELscope as a diagnos,c adjunct in screening lower-risk popula,ons e.g. without a history of dysplasia/oscc, or in pa,ents seen by primary care providers

16 SCREENING AIDS Tissue Fluorescence Spectroscopy Autofluorescence spectroscopy consists of a small op,cal fiber that produces various excita,on wavelengths and a spectrograph that receives and records on a computer and analyzes, via a dedicated so`ware, the spectra of reflected fluorescence from the,ssue This technique has the clear advantage of elimina,ng the subjec,ve interpreta,on of,ssue fluorescence changes. However, the downside is that more variables (e.g. combina,on of wavelengths, methodology of fluorescence analysis etc) have to be tested and considered and this has led to controversial and o`en unclear results

17 SCREENING AIDS Tissue Fluorescence Spectroscopy q Autofluorescence spectroscopy appears to be fairly accurate in dis,nguishing the lesions from healthy oral mucosa, with high sensi,vity and specificity, however, the ability of the technique to dis,nguish and classify different types of lesions is low q Moreover autofluorescence spectroscopy is for prac,cal reasons not suitable to detect new lesions or to demarcate large lesions as the op,cal fiber can sample only a small mucosal area, thus limi,ng the use of spectroscopy to the evalua,on of a well defined small mucosal lesion that has been already iden,fied through visual inspec,on, with the aiempt to clarify its benign or (pre)malignant nature

18 CONCLUSION q A number of molecular markers have been tested too q However, preven,on and early detec,on of OSCC and its pre-invasive intra-epithelial stages is s,ll largely based on visual examina,on of the mouth q In 2005 Dr. Sankaranarayanan and colleagues reported the first robust evidence from a cluster randomized controlled trial, that periodic examina,on of the oral cavity can reduce mortality from oral cancer in high-risk individuals q This study reported a significant 32% reduc,on in mortality in high-risk individuals in the interven,on group (42% when only male tobacco/alcohol users are considered) q Sugges,ng that oral visual screening in high-risk pa,ents could prevent about 40,000 deaths from oral cancer worldwide

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20 MACHINE LEARNING and ARTIFICIAL INTELLIGENCE Rahman, Mohammed S et al. Evalua4on of a Low-Cost, Portable Imaging System for Early Detec4on of Oral Cancer. Head & Neck Oncology 2 (2010): 10. PMC. Web. 26 Nov Methods Reflectance images with white light illumina,on and fluorescence images with 455 nm excita,on were obtained from 261 sites in the oral cavity from 76 pa,ents and 90 sites in the oral cavity from 33 normal volunteers. Quan,ta,ve image features were used to develop classifica,on algorithms to iden,fy neoplas,c,ssue, using clinical diagnosis of expert observers as the gold standard. Results Using the ra,o of red to green autofluorescence, the algorithm iden,fied,ssues judged clinically to be cancer or clinically suspicious for neoplasia with a sensi,vity of 90% and a specificity of 87%.

21 9-VALENT HPV VACCINE q Is likely to protect against HPV associated Anal and Oral Cancers in addi,on to the protec,on that it offers against cervical cancer

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