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Pre-invasive and Invasive Lesions of the Cervix

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Pre-invasive and Invasive Lesions of the Cervix

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Pre-invasive and Invasive Lesions of the Cervix

  1. 1. Pre-invasive & Invasive Lesions of the Cervix http://crisbertcualteros.page.tl
  2. 2. Normal Cervix Cancer Cervical Intraepithelial Neoplasia (CIN) Carcinogenic Factors CIN I CIN II CIN III Carcinogenesis
  3. 8. Carcinogenesis Normal Cervix Cancer Cervical Intraepithelial Neoplasia (CIN) Carcinogenic Factors CIN I CIN II CIN III
  4. 9. Human Papilloma Virus
  5. 10. Predisposing Factors <ul><li>Human Papilloma Virus Infection </li></ul><ul><li>High Grade ( invasive cancer) </li></ul><ul><li>HPV type 16, 18 , 45, 56 </li></ul><ul><li>Intermediate Grade (CIN II / III) </li></ul><ul><li>HPV type 31, 33, 35, 51, 52 </li></ul><ul><li>Low Grade (Condyloma a. / CIN I) </li></ul><ul><li>HPV type 6, 11, 40, 41, 42 </li></ul>
  6. 11. HPV E3 E1 E2 E4 E5 E6 E7 L1 L2 Human Genome p53 pRB Viral Genome Integration
  7. 12. E6 p53 DNA Repair Programmed Cell Death (Apoptosis) Viral Oncoprotein – Host Regulatory Protein Complex
  8. 13. E7 pRB Viral Oncoprotein – Host Regulatory Protein Complex S G2 M G1 G0 cell cycle
  9. 14. Predisposing Factors <ul><li>Sexual behavior </li></ul><ul><li>Early age of first coitus </li></ul><ul><ul><ul><ul><ul><li>Adolescent age group </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Time interval from menarche </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Active cellular proliferation of the transformation zone </li></ul></ul></ul></ul></ul>
  10. 15. Predisposing Factors <ul><li>Sexual behavior </li></ul><ul><li>Multiple sexual partners </li></ul><ul><ul><ul><ul><ul><li>Higher risk of HPV infection </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Likely to have first coitus at an early age </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Epidemiologic studies: rare in celibate women </li></ul></ul></ul></ul></ul>
  11. 16. Normal CANCER INITIATOR PROMOTER Carcinogenesis
  12. 17. Predisposing Factors <ul><li>Oral Contraceptive Pills </li></ul><ul><ul><ul><ul><ul><li>Less likely to use barrier method </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Screening bias: more likely to be seen by a physician regularly </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Associated with Adenocarcinoma </li></ul></ul></ul></ul></ul>
  13. 18. Predisposing Factors <ul><li>Sexual behavior </li></ul><ul><li>Male factor </li></ul><ul><ul><ul><ul><ul><li>Multiple sexual partner </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Uncircumcized </li></ul></ul></ul></ul></ul>
  14. 19. Cervical Intraepithelial Neoplasia
  15. 20. Cervical Intraepithelial Neoplasia <ul><li>Pathology </li></ul><ul><li>Nuclear aneuploidy </li></ul><ul><li>Abnormal mitotic figures </li></ul><ul><li>Loss of maturation of the epithelium </li></ul><ul><li>*Dysplasia CONFINED to the epithelium </li></ul>
  16. 22. Cervical Intraepithelial Neoplasia <ul><li>Subtypes </li></ul><ul><li>CIN I – 1/3 involved </li></ul><ul><li>CIN II – 1/3 – 2/3 involved </li></ul><ul><li>CIN III – 2/3 – whole epithelium </li></ul>
  17. 24. Cervical Intraepithelial Neoplasia <ul><li>Screening Tools </li></ul><ul><li>Cytology ( Papanicolau smear) </li></ul><ul><li>Colposcopy </li></ul><ul><li>HPV DNA Typing </li></ul>
  18. 25. Cervical Intraepithelial Neoplasia <ul><li>Pap Smear </li></ul><ul><li>“ Normal tissue sheds normal cells, abnormal tissue sheds abnormal cells “ </li></ul><ul><li>Samples from the ENDOCERVIX </li></ul><ul><li>and ECTOCERVIX </li></ul>
  19. 26. Cervical Intraepithelial Neoplasia <ul><li>Steps in Doing the Pap Smear </li></ul><ul><ul><ul><li>Insert the speculum lubricated with water only </li></ul></ul></ul><ul><ul><ul><li>Visualize the cervix and vagina </li></ul></ul></ul><ul><ul><ul><li>Sample the endocervix and ectocervix separately </li></ul></ul></ul><ul><ul><ul><li>Spread sample thinly on a labelled glass slide </li></ul></ul></ul><ul><ul><ul><li>Fix sample immediately with 95% ethanol </li></ul></ul></ul><ul><ul><ul><li>Send sample to cytopathologist </li></ul></ul></ul>
  20. 33. Cervical Intraepithelial Neoplasia <ul><li>Pap Smear </li></ul><ul><li>Recommendation: </li></ul><ul><li>Yearly pap smear for women who are sexually active. Then less frequent thereafter if with two successive normal results. </li></ul><ul><li> </li></ul>
  21. 34. Cervical Intraepithelial Neoplasia <ul><li>Pap Smear </li></ul><ul><li>Instructions for the patients: </li></ul><ul><ul><ul><li>No sexual intercourse a day before the smear </li></ul></ul></ul><ul><ul><ul><li>Do not do vaginal douching or use any vaginal lubricant a day before the smear </li></ul></ul></ul><ul><ul><ul><li>No vaginal bleeding (menstruation, etc.) </li></ul></ul></ul>
  22. 35. Cervical Intraepithelial Neoplasia <ul><li>Pap Smear </li></ul><ul><li>Bethesda System (cytopathology report) </li></ul><ul><li>Normal </li></ul><ul><li>Benign cellular changes </li></ul><ul><li>Infection </li></ul><ul><li>Atypical cells of Undetermined significance (ASCUS) </li></ul>
  23. 36. Cervical Intraepithelial Neoplasia <ul><li>Pap Smear (Bethesda System) </li></ul><ul><li>Low Grade Squamous Intraepithelial Lesion (LSIL) </li></ul><ul><ul><ul><ul><ul><li>HPV infection </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>CIN I </li></ul></ul></ul></ul></ul><ul><ul><ul><li>High Grade Squamous Intraepithelial Lesion (HSIL) </li></ul></ul></ul><ul><ul><ul><ul><ul><li>CIN II </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>CIN III </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Glandular Cell Abnormalities </li></ul></ul></ul>
  24. 37. Cervical Intraepithelial Neoplasia <ul><li>Pap Smear </li></ul><ul><li>Pitfalls: </li></ul><ul><ul><ul><li>Sampling error (bloody, inadequate cells, etc.) </li></ul></ul></ul><ul><ul><ul><li>Poor fixation of sample (dry smear) </li></ul></ul></ul><ul><ul><ul><li>Skill of cytopathologist </li></ul></ul></ul>
  25. 38. Colposcopy
  26. 39. Cervical Intraepithelial Neoplasia <ul><li>Colposcopy </li></ul><ul><li>Clinical evaluation of the biochemical and metabolic changes in the cervix as reflected by changes in the: </li></ul><ul><ul><ul><ul><li>Topography of the epithelial surfaces </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Vascular architecture </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li> </li></ul></ul></ul></ul></ul>
  27. 40. Colposcopy of the Cervix
  28. 42. Cervical Intraepithelial Neoplasia <ul><li>Colposcopy </li></ul><ul><li>Indications: </li></ul><ul><ul><ul><li>Abnormal cervical cytology </li></ul></ul></ul><ul><ul><ul><li>Clinically suspicious cervix </li></ul></ul></ul><ul><ul><ul><li>Women with high risk factors for cervical abnormalities </li></ul></ul></ul><ul><ul><ul><li>Women with genital warts or HPV infection </li></ul></ul></ul><ul><ul><ul><li>Women exposed to carcinogens (DES, etc.) </li></ul></ul></ul>
  29. 43. Cervical Intraepithelial Neoplasia <ul><li>HPV DNA Typing </li></ul><ul><li>PCR – most sensitive test </li></ul><ul><li>Prevalence of HPV is dependent on: </li></ul><ul><li> age </li></ul><ul><li> sexual activity </li></ul><ul><li> laboratory technique </li></ul><ul><li> frequency of testing </li></ul>
  30. 44. Cervical Intraepithelial Neoplasia <ul><li>Management </li></ul><ul><li>Cryotherapy </li></ul><ul><li>Ablative procedures </li></ul><ul><li>LEEP / Conization </li></ul><ul><li>Hysterectomy </li></ul>
  31. 47. Cervical Carcinoma
  32. 48. Cervical Carcinoma <ul><li>PUBLIC HEALTH CONCERN </li></ul><ul><li>Most common gynecologic cancer </li></ul><ul><li>Top 5 - Most common cancer in women </li></ul><ul><li>Top 5 - Most common cause of cancer death in women </li></ul><ul><li>Majority present at advanced stage </li></ul>
  33. 50. Cervical Carcinoma <ul><li>Pathology </li></ul><ul><li>Epithelial Tumors </li></ul><ul><li>Squamous Cell Carcinoma </li></ul><ul><li>Large cell, non keratinizing </li></ul><ul><li>Large cell, keratinizing </li></ul><ul><li>Verrucous Carcinoma </li></ul><ul><li>Adenosquamous Carcinoma </li></ul><ul><li>Glassy Cell Carcinoma </li></ul><ul><li>Adenoid Cystic Carcinoma </li></ul><ul><li>Adenoid Basal Epithelioma </li></ul>
  34. 51. Cervical Carcinoma <ul><li>Pathology </li></ul><ul><li>Epithelial Tumors (Adenocarcinoma) </li></ul><ul><li>Mucinous </li></ul><ul><li>Mesonephric </li></ul><ul><li>Endometrioid </li></ul><ul><li>Clear Cell </li></ul><ul><li>Villoglandular </li></ul><ul><li>Papillary Serous </li></ul><ul><li>Minimal deviation </li></ul>
  35. 52. Cervical Carcinoma <ul><li>Pathology </li></ul><ul><li>Neuroendocrine Tumors </li></ul><ul><li>Small Cell Carcinoma </li></ul><ul><li>Large Cell Carcinoma </li></ul><ul><li>Carcinoid Tumors </li></ul><ul><li>Typical </li></ul><ul><li>Atypical </li></ul>
  36. 53. Cervical Carcinoma <ul><li>Symptoms & Pattern of Spread </li></ul><ul><li>Symptoms </li></ul><ul><li>Vaginal bleeding </li></ul><ul><li>Foul smelling vaginal discharge </li></ul><ul><li>Pelvic pain </li></ul><ul><li>Leg edema </li></ul>
  37. 54. Cervical Carcinoma <ul><li>Symptoms & Pattern of Spread </li></ul><ul><li>Pattern of Spread </li></ul><ul><li>Direct invasion of adjacent structures </li></ul><ul><li>Lymphatic invasion </li></ul><ul><li>Hematogenous </li></ul>
  38. 55. Cervical Carcinoma <ul><li>Diagnosis & Staging </li></ul><ul><li>Pelvic examination & Cervical Biopsy </li></ul><ul><li>Chest x-ray </li></ul><ul><li>Colposcopy </li></ul><ul><li>Cystoscopy </li></ul><ul><li>Proctosigmoidoscopy </li></ul><ul><li>Intravenous pyelogram </li></ul><ul><li>Barium enema </li></ul>
  39. 56. Cervical Carcinoma <ul><li>Diagnosis & Staging </li></ul><ul><li>Other tes ts </li></ul><ul><li>CT Scan </li></ul><ul><li>MRI </li></ul><ul><li>PET Scan </li></ul><ul><li>Laparoscopy / hysteroscopy </li></ul><ul><li>Lymphography </li></ul>
  40. 58. Cervical Carcinoma <ul><li>Staging </li></ul><ul><li>Stage I – Carcinoma confined to the cervix </li></ul><ul><li>I A – Microinvasive carcinoma </li></ul><ul><li> IA 1 – Stromal invasion < / = 3.0 mm in depth and < / =7.0 mm in horizontal dimension </li></ul><ul><li> IA 2 – Stromal invasion > 3.0 mm in depth and > 7.0 mm in horizontal dimension </li></ul>
  41. 60. Cervical Carcinoma <ul><li>Staging </li></ul><ul><li>Stage I – Carcinoma confined to the cervix </li></ul><ul><li>I B – Clinically visible lesion </li></ul><ul><li>IB 1 – lesion < / = 4 cms. </li></ul><ul><li>IB 2 - lesion > 4 cms. </li></ul>
  42. 61. Cervical Carcinoma <ul><li>Staging </li></ul><ul><li>Stage II – Carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower vagina. </li></ul><ul><li>II A – No parametrial involvement </li></ul><ul><li>II B – With parametrial involvement </li></ul>
  43. 62. Cervical Carcinoma <ul><li>Staging </li></ul><ul><li>Stage III – Carcinoma extends to the pelvic wall and / or involves the lower third of the vagina or causes hydronephrosis or nonfunctioning kidney. </li></ul><ul><li>III A – Involves lower third of vagina with no extension to the pelvic wall III B – With extension to the pelvic wall and / or hydronephrosis or nonfunctioning kidney </li></ul>
  44. 63. Cervical Carcinoma <ul><li>Staging </li></ul><ul><li>Stage IV – Carcinoma extends beyond the true pelvis or has involved the mucosa of the bladder or rectum (biopsy proven) </li></ul><ul><li>IV A – Spread to adjacent organs </li></ul><ul><li>IV B – Spread to distant organs </li></ul>
  45. 65. Stage III A Stage III B Extension to the LOWER 3rd of Vagina Extension to the PELVIC WALL
  46. 66. Surgical Management
  47. 67. Cervical Carcinoma <ul><li>Surgical Management </li></ul><ul><li>Stage IA 1 – Extrafascial Hysterectomy </li></ul><ul><li>Stage IA 2 to IB 1 and II A </li></ul><ul><li>Radical Hysterectomy with </li></ul><ul><li>pelvic lymphadenectomy </li></ul>
  48. 69. Cervical Carcinoma <ul><li>Surgical Management </li></ul><ul><li>Advantages </li></ul><ul><ul><ul><li>Extent of metastasis evaluated </li></ul></ul></ul><ul><ul><ul><li>Ovaries preserved in young patients </li></ul></ul></ul><ul><ul><ul><li>Treatment duration is short </li></ul></ul></ul><ul><ul><ul><li>Psychological benefit </li></ul></ul></ul><ul><ul><ul><li>Sexual function not impaired </li></ul></ul></ul>
  49. 70. Cervical Carcinoma <ul><li>Surgical Management </li></ul><ul><li>Complications </li></ul><ul><ul><ul><li>Hemorrhage </li></ul></ul></ul><ul><ul><ul><li>Injury to the ureter and adjacent organs </li></ul></ul></ul><ul><ul><ul><li>Infection </li></ul></ul></ul><ul><ul><ul><li>Fistula and lymphocyst formation </li></ul></ul></ul>
  50. 71. Multimodality Treatment
  51. 72. MultiModality Treatment <ul><li>Combination Platinum based chemotherapy AND Radiotherapy </li></ul><ul><li>Chemotherapy: </li></ul><ul><li>- Cisplatin </li></ul><ul><li>- given weekly or every three weeks </li></ul><ul><li>Radiotherapy: </li></ul><ul><li>- External Radiation ( Cobalt, Lin-Acc) </li></ul><ul><li>- Brachytherapy </li></ul>
  52. 79. Cervical Carcinoma <ul><li>Cervical Carcinoma in Pregnancy </li></ul><ul><ul><ul><li>The response to treatment and prognosis of the cancer is not affected by the pregnancy and vice-versa </li></ul></ul></ul><ul><ul><ul><li>Management dependent on the age of gestation of the pregnancy and stage of the cervical cancer </li></ul></ul></ul>
  53. 80. Cervical Carcinoma in Pregnancy <ul><li>Management </li></ul>ChemoRT Stage IB2, IIB, III & IV RHBLND Stage IA2, IB1 & IIA < 20 weeks Management Stage of Cancer Age of Gestation
  54. 81. Cervical Carcinoma in Pregnancy <ul><li>Management </li></ul>* Once with fetal lung maturity CS* + ChemoRT postpartum Stage IB2, IIB, III & IV CS* + RHBLND Stage IA2, 1B1 & IIA >20 weeks Management Stage of Cancer Age of Gestation
  55. 82. Follow-Up
  56. 83. Cervical Carcinoma <ul><li>Follow-up </li></ul><ul><ul><ul><li>Monthly follow-up for the first year and bi-monthly on the second year </li></ul></ul></ul><ul><ul><ul><li>Pap smear every 3 – 6 months </li></ul></ul></ul><ul><ul><ul><li>Chest X-ray every year </li></ul></ul></ul><ul><ul><ul><li>Other imaging studies – dependent on clinical suspicion of recurrence </li></ul></ul></ul>
  57. 85. <ul><li>Please visit: </li></ul><ul><li>http://crisbertcualteros.page.tl </li></ul>

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