Oral epithelial tumors. Markéta Hermanová Human papillomavirus (HPV) nInfect keratinocytes nAssociated with abnormal epithelial proliferation -Hyperplasia – warts -Benign neoplasia – papilloma -Oral premalignant lesion - leukoplakia nMay be present in normal epithelium Benign epithelial lesions associated with human papillomavirus (HPV) nSquamous cell papilloma nVerruca vulgaris (common wart) nCondyloma acuminatum (venereal wart) nFocal epithelial hyperplasia (Heck´s disease) Squamous cell papilloma nUsually solitary nIn adults and children nPedunculated or sesile nMay be warty or cauliflower-like nFinger-like processes of proliferating stratified squamous epithelium supported by fibrovascular cores; hyperkeratosis nNo dysplasia, no premalignant lesion nVerruca vulgaris n- sesile, pedunculated; single, multiple -papillary processes of proliferating stratified squamous epithelium supported by fibrovascular cores; hyperkeratosis -HPV types 2 or 4 nCondyloma acuminatum nFocal epithelial hyperplasia Squamous cell carcinoma - epidemiology nIncidence varies around the world nOne of the 10 commonest cancers nIncidence in developed countries now on the increase nM>F nUsually in people over the age 40 nIncreasing incidence in people aged under 40 years nFatal clinical outcome in 30-40 per cent Aetiological factors in oral cancer nTabacco smoking nSmokeless tabacco (inhalation of powdered tabacco, tabacco chewing) nBetel chewing, betel quid, areca nut nAlcohol (spirit, wine, beer; alcohol and tabacco synergism) nDiet and nutrition (iron deficiency, vit A, C; nutritional deficiencies, alcoholism) nDental factors nUltraviolet light nViruses (HPV, HSV, HIV, EBV) nImmunosuppression nChronic infection (candidosis, syphilis) nOccupation (in agriculture, forestry, fishing – UV light – ca lips; chemicals, dust???) n Tabacco and alcohol nIndependent risk ofooral cancer nSynergistic effecr nRelative risk increases with amount and duration of use nRelative risk influenced by method of use and type nMain carcinogens in tabacco: N-nitrosamines from nicotine nCarcinogenic constituents and/or contaminants in alcoholic drinks nAlcoholic drinks may enhance transport of carcinogens across the mucosal barrier nMucosal barriers impaired by nutritional deficiences in chronic alcohol abuse nLiver disease in alcoholism impair its ability to detoxify carcinogens nImmunosupression in chronic alcohol abuse may increase the risk of developing cancer Diet and oral cancer nDietary deficiences or imbalances may account for 15 per cent of oral cancer nDeficiences of iron and of the antioxidant vitamins A, C, and E increase the risk of oral cancer nDiets high in fresh fruit and vegetables decrease the risk of oral cancer Genetic abnormalities in oral cancer nAccumulation of 6 to 10 genetic alterations in an epithelial cell leading to uncontrolled proliferation and clonal expansion nActivation of oncogenes; inactivation of tumor suppressor genes nGenetic progression model: normal epithelium→dysplasia→carcinoma in situ→invasive cancer nLoss of chromosomal material from specific areas of a chromosome: LOH (loss of heterozygosity) nLOH at 9p – predysplastic lesion n LOH at 3p, 17p (p53 gene)– leading to dysplasia n LOH at 11q, 13q (retinoblastoma gene), 14q – leading to carcinoma in situ n LOH at 6p, 8p, 4q – invasive cancer nOncogenes -Derived from mutated proto-oncogenes in normal cells -Mutation results in enhanced or inappropriate gene expression which may lead to uncontrolled cell growth nTumor suppressor genes -Present in normal cells -Regulatory protein of cell proliferation -Mutation/deletions→defective/deficient protein→uncotrolled celll growth -Mutations in p53 also in oral cancer Molecular basis of cancer onkol The role of tumor suppressor p53 Clinical features of oral squamous cell carcinoma nEarly lesion usually asymptomatic; early detection – determination of prognosis nLocal invasion -Induration and fixation of tissues -Destruction of tissues -Distortion of tissues -Dysfunction of tissues nMetastatic spread to regional lymph nodes -Enlarged, firm nodes -Mobile or fixed nodes n Histopathological features related to prognosis of oral SCC nDiameter of tumor (clinical T stage) nDepth of invasion, incl. bone invasion nNon-cohesive pattern of invasion nPerineural invasion nLymphatic and vascular invasion nMetastatic disease (clinical N and M stage) nExtracapsular spread of nodal metastases n nPrognosis decreases with increasing clinical stage nSite and late onset adversely affect early diagnosis nWorse prognosis in SCC at the back of the mouth: late diagnosis, rich lymphatic drainage around the base of the tongue n Squamous cell carcinoma. Scc _tongue-carcinoma-2 Carcinoma of the tongue. Lymph node metastases nLevel I: nodes of submandibular and submental triangles nLevel II: nodes of upper cervical (jugular) chain nLevel III: nodes of mid-cervical (jugular) chain nLevel IV: nodes of the lower cervical (jugular) chain nLevel V: nodes of posterior triangle of the neck Oral squamous cell carcinoma nWell differentiated nModerately differentiated nPoorly differentiated n nCytologically malignant squamous epithelium nKeratinization varies with degree of differentiation nVerrucous carcinoma (distinctive pathological variety of LG SCC) nBasal cell carcinoma (lips, older people (or in younger with naevoid BCC sy), UV exposure Squamous cell carcinoma spinaliom01 Squamous cell carcinoma spinaliom02 Squamous cell carcinoma spinaliom04 Squamous cell carcinoma spinaliom05 Oral SCC nTongue, base of the oral cavity: the worst prognosis, rapid spread into deep cervical lymph nodes and hematogeneously into lungs nLips: late metastatic spread into submandibular and submentl lymph nodes nGingiva: most frequent at 3rd molar, slower progression n HPV and head and neck SCC nHPV: assoc. with a subgroup of head and neck SCC (most common HPV 16) n nYounger patients, non-smokers, non-alcoholics n nBetter prognosis, better responce to chemotherapy and chemoradiotherapy n nBetter clinical status of patients at diagnosis, earlier diagnosis n nHPV+ carcinomas – half risk of death compared with HPV- carcinomas n nBasaloid morphology, non-keratinising n nHPV associated carcinomas most common arising from tonsilla lingualis and tonsillae palatinales, oropharyngeal Precancerous (or premalignant) lesions and conditions nPrecancerous lesions -Leukoplakia -Erythroplakia -Carcinoma in situ n nPrecancerous conditions -Oral submucous fibrosis -Lichen planus -Actinic keratosis (lips) -Conditions assoc. with epithelial atrophy (e.g. siderophenic dysphagia) Carcinoma in situ 10_01B Basal cell carcinoma (rodent ulcer) nUsually on the skin of the face in elderly patienty (UV exposure) nOccasionally lips (upper) nMultiple naevoid BCC in naevoid BCC syndrome nSlow-growing nodule ncentrally ulcerated 1177364140731_low Thank you for your attention …