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Cin&cancer cervix undergraduate

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undergraduate course lectures in Obstetrics &Gynecology Prepared by Dr Manal Behery Professor of OB&GTNE Faculty of medicine ,Zagazig University

undergraduate course lectures in Obstetrics &Gynecology Prepared by Dr Manal Behery Professor of OB&GTNE Faculty of medicine ,Zagazig University

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Cin&cancer cervix undergraduate

  1. 1. CIN &CANCER CERVIX DR Manal Behery 2014
  2. 2. Introduction – Exocervix – stratified squamous epithelium ● Basal, parabasal, intermediate and superficial layers – Endocervix – cylindrical epithelium, – arranged in branching folds – Squamocolumnar junction
  3. 3. Squamocolumnar junction – Embryogenesis – upward migration of squamous epi from vaginal plate replacing mullerian epi. – Location of SCJ – varies with age & hormonal status ● Everts outwards during adolescence, pregnancy & OCP use ● Regresses into endocervix with menopause, low estrogen states
  4. 4. Transformation zone – Adjacent to SCJ – Most active zone of – squamous metaplasia – – prone to carcinogenic effects
  5. 5. Most active zone of squamous metaplasia
  6. 6. Dysplasia *Lack of normal maturation of cell as they move from basal layer to superficial layer *Large nuclei more variable in size &shape *more actively dividing nuclei. Dysplasia are now referred to as cervical intraepithelial neoplasia ( CIN)
  7. 7. Precursor lesions for cervical cancer
  8. 8. 10 History of the Conventional Pap Smear • Developed by Dr. George N. Papanicolaou in 1940’s • Most common cancer screening test • Key part of annual gynecologic examination Ferris et al. Modern Colposcopy. 2004: 2-4, 49. Photo accessed from http://www.cytology-iac.org/Cytopaths/1998/cytoFall98.htm
  9. 9. 11 Screening with the Conventional Pap Smear • Widely available • Inexpensive • But not perfect – Screening test – not diagnostic – 7-10% of women need further evaluation – Low sensitivity – need regular repeats Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2003; 102:417-27.
  10. 10. 12 New Liquid Pap Tests • More accurate test – Thin, uniform layer of cells – Screening errors reduced by half • Screening needed less often • Can test for HPV with same specimen if abnormal cells found • Expensive Linder J. et al. Arch Pathol Lab Med. 1998; 122: 139-144.
  11. 11. Cervical Cancer Screening Guidelines • First screen 3 years after first intercourse or by age 21 • Screen annually with regular Paps or every 2 years with liquid-based tests • After three normal tests, can go to every three years • Stop at 65-70 years with history of negative tests 13 Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2003; 102:417-27.
  12. 12. Squamo-Columnar Junction • Junction of pink cervical skin and red endocervical canal • Inherently unstable • Key portion of the cervix to sample • Most likely site of dysplasia
  13. 13. Ayers Spatula • Concave end to fit the cervix • Convex end for vaginal wall and vaginal pool scrapings
  14. 14. •Use concave end •Rotate 360 degrees •Don’t use too much force (bleeding, pain) •Don’t use too little force (inadequate sample)
  15. 15. Cytobrush • Insert ~ 2 cm (until brush is fully inside canal) • Rotate only 180 degrees (otherwise will cause bleeding)
  16. 16. Percusion before a Pap Smear – Avoid menstruation – Abstain from intercourse, douching, use of vaginal tampons, or contraceptive creams for min of 24-48 hrs – Avoid touching the cervix before Pap smear – Discharge from cervix may be removed with a swab without touching the cervix
  17. 17. PAP Smear Classification ● The Class System (I to IV) ● The CIN System – Based on degree of cellular abnormalities ● The Bethesda System
  18. 18. Bethesda (2001) reporting of Pap Smear: – Specimen type – conventional, LBC – Specimen adequacy – satisfactory, unsatisfactory – General Categorisation: ● Negative for intra-epithelial lesion ● Epithelial cell abnormality ● Glandular cell abnormality
  19. 19. COLPOSCOPY
  20. 20. In office Colposcopy done after an abnormal pap smear result Vinegar solution is applied to cervix, abnormal tissue will turn white in color ACETOWHITE ARES
  21. 21. 27 Fig. 6 Punctation seen with carcinoma-insituand microinvasion. Fig. 8 Loop diathermy apparatus
  22. 22. Guidelines for colposcopy – Negative for intraepithelial abnormality – routine cytological screening – ASC-H, LSIL, HSIL – colposcopy and biopsy – AGC – colposcopy, endocervical and endometrial evaluation – AIS – excision biopsy
  23. 23. Risk factors – HPV Infection – Cigarette smoking – Parity – Oral Contraceptive use – Early sexual activity, Multiple partners – STDs – Chronic Immunosuppression
  24. 24. The HPV Life Cycle JA Kahn, NEJM, 2009;361:271
  25. 25. 31 Natural history of HPV infection to Cervical cancer 0–1yrs 0–5yrs CCeerrvviiccaall CCaanncceerr Persistent infection Low Grade Precancers (CIN 1) 1–20yrs HPV infection High Grade Precancers (CIN 2/3) Recovery: HPV clearance…90% Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43:352–362.
  26. 26. HVP vaccination • The vaccine only worked in women and girls who were not already infected with HPV. • Gardasil (2006) or Cervarix (2009) are routinely given to 11- and 12-year-old girls, and allowed for girls as young as 9.
  27. 27. RReeaall VVaacccciinnee VViirruuss 33 HPV Vaccine technology GARDASIL is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA. *VLP = Virus-like particle. 1. Villa LL, Costa RL, Petta CA, et al. Lancet Oncol. 2005;6:271–278. Image courtesy of Dr. Ian Frazer – Empty Shell formed by recombinant biotechnology to mimic the viral 3D shape. – Does not contain infectious DNA。
  28. 28. 34 Dosing schedule GARDASIL Intramuscular injection (IM) Recommended schedule 3 doses at month 0,2,6 month CERVARIX Vaccine: 3 doses at month 0,1,6
  29. 29. 35 HPV vaccine is for men and women To prevent vaccine type related Female: Cervical 、vaginal、vulvar Cancers and genital warts Male: + 4-in-1 HPV vaccination Regular Pap screening
  30. 30. LEEP VS Conization
  31. 31. Cervical carcinoma
  32. 32. Understanding Cancer • Normally, cells grow and divide to form new cells as the body needs them. When cells grow old, they die, and new cells take their place.
  33. 33. Understanding Cancer • Sometimes, this orderly process goes wrong. New cells form when the body does not need them, and old cells do not die when they should. These extra cells can form a mass of tissue called a growth or tumor.
  34. 34. Background • Worldwide, cervical cancer is the 2nd leading cause of cancer death in women • Squamous cell carcinoma (85%) • Adenocarcinoma (15%) • Risk factors for squamous cell cancer – Early coitarche – Greater than 6-8 partners – Cigarette smoking – Oral contraceptives
  35. 35. • Cervical cancer is most strongly associated with sexually transmitted HPV infection • During the sexual lifespan of a woman, approximately 70% will have been exposed to HPV • HPV subtypes are classified into high and low risk groups
  36. 36. Clinical Picture ● Asymptomatic ● Vaginal Bleeding – Post coital – Intermenstrual spotting – Irregular or Postmenopausal bleeding ● Discharge P/V ● Pain referred to flanks ● Dysuria, hematuria, rectal bleeding ● Massive Haemorrhage, uraemia
  37. 37. Diagnosis 1- History. • Many women are a symptomatic . • Presented with abnormal routine cx smear • Complain of abnormal vaginal bleeding • I M bleeding • post coital bleeding • perimenopausal bleeding • postmenopausal bleeding • blood stain vaginal discharge
  38. 38. 2- Examination: • PV exam using cuscu’s speculem • nothing is found in early stage . • Mass ,ulcerating fungating in the cervix • P/V P/R is very helpful.
  39. 39. Investigations ● Physical Examination – Lymph node examination – Per Vaginum – Bimanual rectovaginal examination ● Radiology Colposcopy – IVP CX biopsy – Barium Enema – X Ray Chest – Skeletal X Ray
  40. 40. Cervical Biopsy – Punch biopsy – LEEP ● Outpatient procedure ● Diagnosis and therapy at same time ● Main side effect – secondary haemorrhage
  41. 41. Conization – Cold knife – Laser – If cut margins free from cancer, then almost 100% disease free follow-up
  42. 42. CT and MRI – Evaluation of lymphnodes, liver, urinary tract and bony structures – Can detect only changes in size of nodes, < 1cm considered as positive
  43. 43. Patterns of spread • Direct invasion cervical stroma, vagina, and parametrium. • Lymphatic spread pelvic and then par aortic lymph nodes • Hematogenous spread such as lungs, liver, and bone
  44. 44. Lymphatic Spread – Primary Group ● Parametrial nodes ● Paracervical/ureteral nodes ● Obturator nodes ● Hypogastric nodes ● External iliac nodes ● Sacral nodes – Secondary Group ● Common Iliac nodes ● Inguinal nodes (deep and superficial) ● Periaortic nodes
  45. 45. Cervical carcinoma staging • Staging is clinical • FIGO staging • Based on EUA, cystoscopy +/- sigmoidoscopy • Does NOT include MRI
  46. 46. FIGO Staging (2009) ● Stage I – carcinoma confined to cervix – IA: invasive carcinoma diagnosed microscopically. Stromal invasion depth upto 5 mm and width less than 7 mm ● IA1 – stromal invasion <3mm depth and <7mm width ● IA2 – stromal invasion 3-5 mm and <7mm width – IB: clinically visible lesion confined to the cervix ● IB1 – lesion <4 cm or less ● IB2 – lesion >4 cm
  47. 47. Stage II – carcinoma invading beyond uterus but not to pelvic wall or lower 1/3 of vagina – IIA – Tumour without parametrial invasion ● IIA1 – lesion < 4 cm ● IIA2 – lesion > 4 cm – IIB – Tumour with parametrial invasion
  48. 48. Stage III – tumour extending to lateral pelvic wall/lower third of vagina ● causing hydronephrosis or non-functioning kidney – IIIA – Tumour involves lower 1/3 of vagina, no extension to pelvic wall – IIIB – Tumour extends to pelvic wall or causing hydronephrosis/non-functioning kidney
  49. 49. Stage IV
  50. 50. Cervical cancer prevention: Widespread introduction of the Pap begins Where have we been and where Conventional Pap smear LBC 1949 1996 2000’s HPV testing Vaccine are we going? Markers
  51. 51. The choice of treatment will depend on • Fitness of the patients • Age of the patients • Stage of disease. • Type of lesion • Experience and the resources available.
  52. 52. Therapy Cervical conization Simple hysterectomy Radical hysterectomy Radiation therapy with chemosensitization
  53. 53. Stage 1 disease • Treatment = LLETZ • Conization
  54. 54. Stage 1 disease • Confined to cervix • Treatment • = surgical for 1B1 • Chemo Radiotherapy for 1B2
  55. 55. Surgical procedure • The classic surgical procedure is the wertheim’s hystrectomy for stage Ib,IIa, and some cases of IIb in young and fat patient
  56. 56. Werthemeim’s hystrectomy • Total abdominal hystrectomy including the parametrium. • Pelvic lymphadenectomy • 3 cm vaginal cuff • The original operation conserved the ovaries ,since squamouss cell carcinoma does not spread dirctly to the ovaries. • Oophorectomy should be performed in cases of adenocarcinoma as there is 5-10% of ovarian metastosis
  57. 57. 5 year Survival • Stage I 70% • Stage II 51% • Stage III 33% • Stage IV 17%
  58. 58. COMPLICATIONS OF SURGERY • Haemorrhage: primary or secondary. • Injury to the bladder, uerters. • Bladder dysfunction. • Fistula. • Lymphocele. • Shortening of the vagina.
  59. 59. Lymphedema
  60. 60. Radiation theRapy
  61. 61. Radiation Therapy External Beam Whole pelvis or para-aortic window 4000-6000 cGy Over 4-5 weeks Brachytherapy Intracavitary or interstitial 2000-3000 cGy Over 2 implants
  62. 62. Pros and Cons Surgery Bladder dysfunction Vesico/uretero fistula Bowel obstruction Ovarian preservation Vaginal preservation Radiation Sigmoiditis Rectovaginal fistula Bowel obstruction Vesico/uretero fistula Ovarian failure
  63. 63. Staging and treatment • Surgical in women up to stage 1b1 • Chemotherapy • (cisplatin) ± radiotherapy • with disease > stage 1b1

Hinweis der Redaktion

  • Primary cervical cancer screening essentially began with the introduction of the Pap Smear.
    Introduced in the 1940’s, by Dr. George N. Papanicolaou, the pap smear eventually became the standard screening test for cervical cancer and pre-malignant lesions.
    The Pap test is based on a relatively simple principle. Cells from squamous epithelium exfoliate over time. Thus, the cells removed for cytologic examination represent epithelial cells, normal or abnormal, found at the surface.
    Widespread use of the pap smear has decreased cervical cancer deaths by 70%.
    Reference: Ferris et al. Modern Colposcopy. 2004: 2-4, 49.
  • Cervical cytology screening is, in many respects, the ideal screening test.
    Cervical cancer has a defined premalignant phase of many years, which allows repeated tests to significantly reduce the impact of individual false-negative test results.
    Cervical cytology is inexpensive and is readily accepted among American women.
    However, cervical cytology, is not a diagnostic test. The sensitivity of the pap smear is low (ranges from 47-85%) and the specificity is high (95-98%).
    Reference: Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2003; 102:417-27.
  • In 1996, the FDA approved the first of two currently available liquid-based thin-layer cytology preparations for cervical screening.
    Liquid-based thin-layer cervical cytology was introduced to help reduce the potential sampling errors. The Thin-Prep method appears to have increased sensitivity for detecting cancer precursor lesions over the conventional method, but the degree to which sensitivity is increased is unknown. The reported increase in sensitivity may make this method especially useful in women who are screened infrequently (fewer false negatives).
    The difference in specificity between the liquid-based and conventional tests has not been determined. Although an increase in sensitivity will permit earlier detection of cancer precursor lesions, any decrease in specificity can result in increased cost and morbidity from false-positive diagnoses.
    Both the conventional test and the liquid-based thin-layer test can be effective in population screening.
    Providers selecting a cervical cytology method should consider the screening history of their patient, the cost of the test, and the possible effects of false-negative or false-positive results.
    Reference: ACOG Practice Bulletin. Cervical Cytology Screening. 2003; 45:1-11.
  • The next several slides will review the newest guidelines for cervical cancer screening from the American Cancer Society, the United States Preventive Services Task Force and the American College of Obstetricians and Gynecologists.
    These guidelines specifically state how often screening should be done, when to initiate screening and when screening can be discontinued.
    Reference: Cervical Cytology Screening. ACOG Practice Bulletin No. 45. 2003; 102:417-27.
  • In obtaining the Pap smear, it is important to sample the &amp;quot;Squamo-columnar Junction.&amp;quot; This is the circular area right at the opening of the cervix where the pink, smooth skin of the cervix meets the fiery-red, fragile, mucous-producing lining of the cervical canal. If there is going to be a problem with cancer or precancerous changes, it is this area that is most likely to be effected. This area is also known as the SQJ, or transition zone.
  • The Ayers spatula is specially designed for obtaining Pap smears. The concave end (curving inward) fits against the cervix, while the convex end (curving outward) is used for scraping vaginal lesions or sampling the &amp;quot;vaginal pool,&amp;quot; the collection of vaginal secretions just below the cervix.
    The spatula is made of either wood or plastic. Both give very satisfactory results.
  • Push the cytobrush into the canal, no deeper than the length of the brush (1.5 cm - 2.0 cm). Rotate the brush 180 degrees (half a circle) and pull the cytobrush straight out. Don&amp;apos;t keep spinning the brush round and round or you will cause bleeding. Even the 180 degree rotation may cause a little bleeding but usually it doesn&amp;apos;t.
  • Despite these strong results, experts say women still need to get regular Pap tests to look for cervical cancer.
    The HPV types targeted by the vaccine aren&amp;apos;t the only ones that can cause cancer, so even vaccinated women aren&amp;apos;t 100% protected from this disease. Furthermore, it&amp;apos;s been only about 5 years since studies began; the participants are still being followed to see how long the vaccine&amp;apos;s protection will last.
    And, the vaccine only worked in women and girls who were not already infected with HPV 16 or 18. That&amp;apos;s why federal health officials and the American Cancer Society recommend giving Gardasil routinely to 11- and 12-year-old girls, and allow it for girls as young as 9. Vaccinating girls before they become sexually active and have a chance to catch HPV gives them the best chance of being protected by the vaccine.
  • Cancer begins in cells, the building blocks that make up tissues. Tissues make up the organs of the body.
    Normally, cells grow and divide to form new cells as the body needs them. When cells grow old, they die, and new cells take their place.
  • Sometimes, this orderly process goes wrong. New cells form when the body does not need them, and old cells do not die when they should. These extra cells can form a mass of tissue called a growth or tumor.
    Tumors can be benign or malignant.
  • Slide 19:
    In recent decades, concerns about the sensitivity of conventional cervical cytology led to the evaluation of alternatives. (Bullet 1) Liquid based cytology (LBC) was first introduced into clinical practice following the 1996 FDA-licensing of a thin layer cytology system. (Bullet 2) An HPV test using hybrid capture technology was FDA-approved for the management of ASC-US Pap results in 1999 and as a co-test with the Pap for women ages 30 and over in 2003. A newer signal amplification HPV DNA test and type-specific test for HPV 16 and18 were licensed by the FDA for clinical use in early 2009. (Bullet 3) An HPV vaccine became available when the FDA licensed a quadrivalent vaccine in June, 2006. This vaccine was approved for use in girls and women 9-26 years of age and included protection against two high risk and two low risk HPV types. A second HPV vaccine became available after the FDA licensed a bi-valent HPV vaccine, for the prevention of two high risk types, in October, 2009, for use in females up to age of 25 (Bullet 4) In the future, other bio-markers for increased risk for cervical cancer, such as mRNA and P16 are expected to be introduced to the market.
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