2. Cancer of Cervix Shashi. Oct-15 Introduction: Best example of cancer prevention. Best example of cancer prevention. US Statistics: US Statistics: Leading cause - PAP – 8 th Cause. >60% Leading cause - PAP – 8 th Cause. >60% Over 1M PAP positive & 13,000 invasive/y Over 1M PAP positive & 13,000 invasive/y Potentially curable if detected early Potentially curable if detected early Long pre-cancer state. Long pre-cancer state. Shed abnormal cells – cytological test - PAP Shed abnormal cells – cytological test - PAP Easy access to biopsy and treatment. Easy access to biopsy and treatment.

3. Cancer of Cervix Shashi. Oct-15 Pathogenesis: Early age at sex, Multiple partners. Early age at sex, Multiple partners. Oral contraceptives, smoking, F hist etc. Oral contraceptives, smoking, F hist etc. HPV infection – central to cancer (>85%) HPV infection – central to cancer (>85%) High risk types – 16, 18, 31, 33 (Bound-DNA) High risk types – 16, 18, 31, 33 (Bound-DNA) Low risk types – 6, 11, 42-44 (Free DNA) Low risk types – 6, 11, 42-44 (Free DNA) Oncogene E6 (p53) & E7 (Rb) Oncogene E6 (p53) & E7 (Rb) Other viral/mutations can cause rarely. Other viral/mutations can cause rarely.

4. Cancer of Cervix Shashi. Oct-15 Cervical Transformation Zone Pathogenesis: Sexual Exposure HPV Infection Squamous Ep Columnar Ep Squamous Ca Adeno Ca High Risk Types (16,18) Low Risk-6,11 Smoking, Hormone, Oral contr. parity, Altered immune response etc.

5. Cancer of Cervix Shashi. Oct-15 Cervical Intraepithelial Neoplasia (CIN) Dysplasia within Ep. – (no infiltration) Dysplasia within Ep. – (no infiltration) Squamo-Columnar junction – common site Squamo-Columnar junction – common site Dysplasia + Koilocytes - Plenty of HPV DNA Dysplasia + Koilocytes - Plenty of HPV DNA May Progress or Regress - Risk of cancer. May Progress or Regress - Risk of cancer. Classification: Classification: Mild – Moderate – Severe dyspalasia0 (CIS) Mild – Moderate – Severe dyspalasia0 (CIS) CIN-I, CIN-II & CIN-III (CIS) CIN-I, CIN-II & CIN-III (CIS)

6. Cancer of Cervix Shashi. Oct-15 Normal Cervix:

7. Cancer of Cervix Shashi. Oct-15 Condyloma Cx.

8. Cancer of Cervix Shashi. Oct-15 Normal Cervix : SUPER F INTERMBASAL

9. Cancer of Cervix Shashi. Oct-15 Cervical Dysplasia:

10. Cancer of Cervix Shashi. Oct-15 Cervical HPV infection:

11. Cancer of Cervix Shashi. Oct-15 Pap Smear Results:

12. Cancer of Cervix Shashi. Oct-15 Morphology: Raised (acuminatum) or flat (macular). Raised (acuminatum) or flat (macular). Koilocytotic atypia Koilocytotic atypia Abundant HPV nucleic acids. Abundant HPV nucleic acids. Atypical cells in the basal region (CIN-1) or completely replace normal cells (CIN-3) Atypical cells in the basal region (CIN-1) or completely replace normal cells (CIN-3)

13. Cancer of Cervix Shashi. Oct-15 Ca Cx - Morphology 3 gross types 3 gross types Exophytic/Fungating, Ulcerating & Infiltrative. Exophytic/Fungating, Ulcerating & Infiltrative. 80% Squamous-Ca, 20% other. 80% Squamous-Ca, 20% other. Adeno-carcinoma, Adenosquamous, Clear- cell carcinoma etc. Adeno-carcinoma, Adenosquamous, Clear- cell carcinoma etc. 40-50 peak age. 40-50 peak age.

14. Cancer of Cervix Shashi. Oct-15 Staging: Stage 0 – CIN-III Stage 0 – CIN-III Stage 1 – Ca limited to Cx Stage 1 – Ca limited to Cx 1a – Preclinical – diagnosed by microscopy 1a – Preclinical – diagnosed by microscopy 1a1- Minimal invasive 1a1- Minimal invasive 1a2 – Microscopic invasion <5mm 1a2 – Microscopic invasion <5mm 1b – more than 5 mm invasion 1b – more than 5 mm invasion Stage 2 – Beyond but pelvic wall free Stage 2 – Beyond but pelvic wall free Stage 3 – Pelvic wall/lower vagina involve Stage 3 – Pelvic wall/lower vagina involve Stage 4 – Extension beyond pelvis. Stage 4 – Extension beyond pelvis.

15. Cancer of Cervix Shashi. Oct-15 Clinical Features: Asymptomatic – Abnormal cells in smears Asymptomatic – Abnormal cells in smears Vaginal Bleeding Vaginal Bleeding Treatments – Cone biopsy, hysterectomy Treatments – Cone biopsy, hysterectomy 5 year survival 5 year survival Stage1->80%, Stage2–75%, Stage3-35% & 10-15% with Stage 4 disease. Stage1->80%, Stage2–75%, Stage3-35% & 10-15% with Stage 4 disease.

16. Cancer of Cervix Shashi. Oct-15 Ulcerating Ca Cx:

17. Cancer of Cervix Shashi. Oct-15 Fungating Ca Cx

18. Cancer of Cervix Shashi. Oct-15 Stage IV – Ca Cx (Block Dissection)

19. Cancer of Cervix Shashi. Oct-15 Spread: Direct: Direct: Down – Vagina, Labia Down – Vagina, Labia Lateral – adnexa, ureter, ovary, Pelvic wall Lateral – adnexa, ureter, ovary, Pelvic wall Anterior – bladder Anterior – bladder Posterior – Rectum Posterior – Rectum Lymphatic: Lymphatic: Paracervical, Obturator, Int & Ext iliac, Sacral,Common iliac, Aortic. Paracervical, Obturator, Int & Ext iliac, Sacral,Common iliac, Aortic. Blood: Liver, lungs etc. Blood: Liver, lungs etc.

20. Cancer of Cervix Shashi. Oct-15 Stage IV – Ca Cx (Block Dissection)

21. Cancer of Cervix Shashi. Oct-15 Carcinoma Cervix:

22. Cancer of Cervix Shashi. Oct-15 Infiltrating Carcinoma Cx:

23. Cancer of Cervix Shashi. Oct-15 Squamous Carcinoma:

24. Cancer of Cervix Shashi. Oct-15 Summary: Carcinoma cervix is related to HPV infection with other risk factors. (smoking) Carcinoma cervix is related to HPV infection with other risk factors. (smoking) Early diagnosis by cytological PAP test. Early diagnosis by cytological PAP test. Predominantly Squamous type(80%). Predominantly Squamous type(80%). Clinically divided into 1- 4 stages. Clinically divided into 1- 4 stages. Spread by direct, lymphatic & blood. Spread by direct, lymphatic & blood.