Human Papilloma Virus (HPV) and Cervical Cancer PDF

HUMAN PAPILLOMA VIRUS (HPV) Responsible for dysplastic changes within the mucosal epithelium, most commonly in the cervix Low risk HPV types 6 & 11: low grade intraepithelial neoplasia (anogenital warts or condyloma accuminatum); potentially premalignant High risk HPV types 16 &18: high...

HUMAN PAPILLOMA VIRUS (HPV) Responsible for dysplastic changes within the mucosal epithelium, most commonly in the cervix Low risk HPV types 6 & 11: low grade intraepithelial neoplasia (anogenital warts or condyloma accuminatum); potentially premalignant High risk HPV types 16 &18: high grade intraepithelial neoplasia; premalignant  KOILOCYTE Hallmark of HPV infection in an epithelium “Raisinoid” nucleus (enlarged, hyperchromatic, irregular), perinuclear halo and cytoplasmic thickening Upper epithelial layer  PAP SMEAR SCREEN PAP screening has reduced incidence of cervical cancer (SCC) from leading cancer killer of women (50 years ago) to eighth leading cause today PAP screen successful because – Koilocytes and dysplasia are detectable – Most cervical cancer is preceded by these precancerous changes  PAP SMEAR SCREEN NORMAL LSIL HSIL HSIL  CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) Three grades of severity: – CIN I: mild dysplasia – CIN II: moderate dysplasia – CIN III: severe dysplasia (highest risk for progression to invasive squamous cell carcinoma) Progression to invasion may take from a few months to twenty years; unpredictable CERVICAL TRANSFORMATION ZONE NORMAL PREINVASIVE  SQUAMOUS CELL CARCINOMA (CERVIX, VAGINA, VULVA) Peak incidence 40 - 45 years Spreads by direct extension into any neighboring structures (bladder, rectum, vagina, peritoneum, ureters) Regional and distant metastasis: regional lymph nodes, lungs liver, and bone.  SQUAMOUS CELL CARCINOMA OF CERVIX NORMAL SQUAMOUS CELL CARCINOMA  SQUAMOUS CELL CARCINOMA May take years to evolve with only sign of its presence the atypical cells shed from the cervix and found by the PAP screen Invasive cancers usually trigger hysterectomy and possibly radiation SLIDES Actinic keratosis (also called "solar keratosis” and "senile keratosis”) lichenoid form Actinic keratosis (also called "solar keratosis” and "senile keratosis”) hyperplastic form Keratosis praecancerosa atrophica vel simplex - zmiany o małej aktywności rozrostowej nie stanowiące bliskiego zagrożenia rakiem; naskórek cienki, z patologicznym rogowaceniem ( zbite blaszki parakeratotyczne). Keratosis praecancerosa atrophica vel simplex Keratosis activa v.praecancerosa hypertrophica ( proliferans) Leukoplakia Dysplasia benigna mammae. (cystical changes and microcalcifications) Dysplasia benigna mammae. (hyperplastic changes ). Dysplasia benigna mammae.( apocrine metaplasia) Verruca seborrhoica, Seborrhoeic wart (seborrhoeic keratosis)  Tumor Growth Rate Doubling time of tumor cells – Lengthens as tumor grows – 30 doublings (109 cells) = 1 g (months to years) – 10 more doublings (1 kg) = lethal burden (“) Fraction of tumor cells in replicative pool – May be only 20% even in rapidly growing tumors – Tumor stem cells Rate at which tumor cells are shed or lost – Apoptosis – Maturation Implications for therapy Schematic Representation Of Tumor Growth  Features of Malignant Tumors Cellular features Local invasion – Capsule – Basement membrane Metastasis – Unequivocal sign of malignancy – Seeding of body cavities – Lymphatic – Hematogenous  Benign vs Malignant Features Feature Benign Malignant Rate of growth Progressive but Variable. Mitoses slow. Mitoses more frequent few and normal and may be abnormal Differentiation Well Some degree of differentiated anaplasia Local invasion Cohesive growth. Poorly cohesive Capsule & BM and infiltrative. not breached Metastasis Absent May occur  Geographic & Environmental Sun exposure – Melanomas 6x incidence New Zealand vs Iceland – Blacks have low incidence of melanoma Smoking and alcohol abuse Body mass – Overweight = 50% increase in cancer Environmental vs racial factors – Japanese immigrants to USA Viral exposure – Human papilloma virus (HPV) and cervical cancer – Hepatitis B virus (HBV) and liver cancer (Africa) – Epstein-Barr Virus (EBV) and lymphoma  Predisposing Factors for Cancer Age – Most cancers occur in persons ≥ 55 years – Childhood cancers Leukemias & CNS neoplasms Bone tumors Genetic predispostion – Familial cancer syndromes Early age at onset Two or more primary relatives with the cancer Multiple or bilateral tumors – Polymorphisms that metabolize procarcinogens, e.g., nitrites Nonhereditary predisposing conditions – Chronic inflammation – Precancerous conditions Chronic ulcerative colitis Atrophic gastritis of pernicious anemia Leukoplakia of mucous membranes  MOLECULAR BASIS of CANCER nNON-lethal genetic damage nA tumor is formed by the clonal expansion of a single precursor cell (monoclonal) nFour classes of normal regulatory genes n PROTO-oncogenes n Oncogenesà Oncoproteins n DNA repair genes n Apoptosis genes nCarcinogenesis is a multistep process  TRANSFORMATION & PROGRESSION Self-sufficiency in growth signals Insensitivity to growth-inhibiting signals Evasion of apoptosis Defects in DNA repair: “Spell checker” Limitless replicative potential: Telomerase Angiogenesis Invasive ability Metastatic ability Normal CELL CYCLE Phases INHIBITORS: Cip/Kip, INK4/ARF Tumor (really growth) suppressor genes: p53