Cervical Neoplasia

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  • Pienso que esta le puede ayudar a hacer la introducción acerca del porque la importancia del HPV y luego concretar un poco con la epidemiologia.
    SE PUEDE PRECINDIR DE ESTA
    Estimated Prevalence of Genital HPV Infection in the USA
    (figure adapted from Koutsky, Am J Med, 1997)
    This pyramid illustrates the estimated prevalence of genital HPV infection among men and women 15-49 years of age in the USA.1-3 Only a very small percentage of those infected with the HPV virus actually develop genital warts.
    The estimated population in this age group in 1995 >135 million. An overall estimate is that 15% of this population (at least 20 million adults) is infected.1,3
    The prevalence of genital warts is higher in certain populations, especially those attending STD clinics. In a study of patients attending a Seattle STD clinic in 1986, 13% of men and 9% of women had condylomata.3
    Estimates based on similar research suggest the global prevalence of condylomata is between 1-2% of the sexually active population 15-49 years of age.
    References
    1. Koutsky L. Epidemiology of human papillomavirus infection. Epidemiol Rev. 1988;10:122-63
    2. US Bureau of the Census. Statistical Abstracts of the United States, 1996.
    3. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med. 1997;102(5A):3-8
  • HPV Malignant Transformation
    All types of HPV replicate exclusively in the host cell's nucleus.1
    In benign HPV-associated skin lesions, HPV exists as a plasmid in the cell's cytoplasm. It replicates separately, extrachromosomally.1
    In malignant HPV-associated skin lesions, HPV integrates into the host cell's chromosome. In order to do this, a break must occur in the viral genome. This mostly occurs around the E1/E2 region.1
    As a result of this break, the function of E1 and E2 is lost, and the function of E6 and E7 is deregulated, resulting in cellular transformation.1
    It is thought that the E6 gene binds to the p53 protein, a tumour suppressor protein, leading to malignant transformation and loss of regulated cell growth.1
    It is thought that the E7 gene binds to the retinoblastoma gene product (another tumour-suppressor protein), the effect of which is to disrupt control of cell cycle progression.2
    References
    1.Beutner KR, Tyring S. Human papillomavirus and human disease. Am J Med. 1997;102(5A):9-15.
    2.Phelps W, Alexander KA. Antiviral therapy for human papillomaviruses: rationale and prospects. Ann Intern Med. 1995;123:368-382.
  • Esta es reubicable
  • Esta es reubicable
  • Basement membrane intact, then invasive cancer, this cannot kill, this can
  • Cervical Neoplasia

    1. 1. Cervical Neoplasia Cervical Dysplasia Cervical Carcinoma Concepcion Diaz-Arrastia, M.D. Assistant Professor University of Texas Medical Branch Department of Obstetrics and Gynecology Division of Gynecologic Oncology
    2. 2. HPV Infection and Cervical Cancer HPV % 16 59% 18 12% 45 4.8% 31 3.7% 33,35,51,52,58,59 Odds Ratio 182 231 148 71.5 35-146 Carcinogenic by epidemiologic definition
    3. 3. ESTIMATED PREVALENCE OF GENITAL HPV INFECTION IN THE USA Genital warts Subclinical infection (colposcopy) Subclinical infection (PCR, RT- PCR) Prior infection (antibodies) No prior or current infection Koutsky, Am J Med. 1997Koutsky, Am J Med. 1997 25% 60% 10% 4% 1%
    4. 4. Human Papilloma Virus • > 130 HPV genotypes – definition: <10% difference L1 major capsid protein – or >50% sequence homology • > 20 Anogenital tract – high risk – low risk
    5. 5. EPIDEMIOLOGY OF HPV INFECTION LUDWIG/MCGILL COHORT STUDY Prevalence HPV 13.8 % Non-oncogenic: 5 months Oncogenic: 8 months 38.9% HPV (+) by 18 months Franco, et al. JID 1999;180-1415-23.
    6. 6. HPV is Epitheliotropic • No viremia • Infection is confined to where it initiated • Spreads by infected cell dividing.
    7. 7. Courtesy of Dr. Tung Van Dinh
    8. 8. Courtesy of Dr. Tung Van Dinh
    9. 9. HPV Malignant Transformation Beutner, Am J Med, 1997 Extrachromosomal HPV DNA Integrated HPV genes Host chromosome Benign growth or wart Malignant tumour Deregulated expression of HPV E6 and E7 Interactions with cellular regulatory proteins
    10. 10. High Risk HPV typesHigh Risk HPV types are ONCOGENICare ONCOGENIC
    11. 11. Co-Factors Persistence and Progression • Age at acquiring infection • Genetically determined immune characteristics – Human Leukocyte Antigen (HLA) type – Variant metabolizing genes ---Tobacco • Hormonal factors – HPV transcriptional regulation has estrogen recognition sites • Diet: low carotenoids • STD’s: cervico-vaginal inflammation – Chlamydia, HSV-2, HIV, HPV co- infections
    12. 12. HPV INFECTION Epithelium at Risk of HPV infection • Cervical • Vaginal • Vulvar • Anal – Men and women – Anal receptive intercourse – Anal Pap smear – Anal Colposcopy of Transformation Zone
    13. 13. Incidence of Carcinoma Epithelium at Risk Cervical 8 - 52 / 100,000 Anal (at risk population) 35 / 100,000
    14. 14. A comparison of three management strategies for patients with Atypical Squamous Cells of Undetermined Significance C o n e B io p s y 1 3 6 I m m e d ia t e c o lp o s c o p y 1 1 6 3 H P V ( - ) C o n e B io p s y 1 4 3 C o lp o s c o p y H P V ( + ) 6 5 1 H P V t r ia g e 1 1 6 1 C o n e B io p s y 6 9 C o lp o s c o p y R e p e a t p a p a b n o r m a l 1 0 1 C o n s e r v a t iv e m a n a g e m e n t 1 1 6 4 3 4 8 8 r a n d o m iz e d T y p e t itle h e r e
    15. 15. HPV RESULTS BY HC 2† Cytology Negative (%) Positive (%) Negative 934 (64.0) 453 (31.01) ASCUS 541 (47.7) 555 (48.9) LSIL 67 (10.6) 525 (83.3) HSIL-CIN2 7.(3.4) 191. (92.3) HSIL- CIN3+ 0 (0) 36 (92.3) TOTAL 1558 (44.7) 1766 (50.6)
    16. 16. Work-up of Abnormal Pap Smear • HPV typing – ASCUS • Colposcopy and directed biopsy – All other abnormalities
    17. 17. Colposcopy The Transformation Zone • Colposcopy – Long focal length dissecting microscope – 16 X – Acetic acid 3-5% • Biopsy any visible lesion • Endocervical Curettage – if not see lesion entirely / at all
    18. 18. NATURAL HISTORY OF Cervical Intraepithelial Neoplasia Regress Persist Progress CIN1 60% 30% 10% CIN2 40% 40% 20% CIN3 33% 55% >12% invasive cancer HGCIN LGCIN
    19. 19. Treatment of Low Grade Intraepithelial Neoplasia (CIN 1) Observation – 60% Spontaneous regression
    20. 20. Surgical Treatment of High-Grade Dysplasia ABLATION EXCISION Cone Biopsy - Cryotherapy - LASER Excision - Laser Ablation - LEEP (Loop electrocautery excision procedure) - Cold Knife No Specimen Specimen produced >90% effective
    21. 21. INCIDENCE OF CERVIXINCIDENCE OF CERVIX CARCINOMACARCINOMA
    22. 22. CERVICAL CANCER Patient Presentation 25% Abnormal Pap
    23. 23. CERVICAL CANCER Patient Presentation 25% Abnormal Pap 75% Symptoms / gross disease • 30% Never had a Pap • 25% “Normal” Pap within 5 years • 20% “Normal” Pap within 1 year
    24. 24. Cervical Carcinoma Symptoms 1) Post Coital Bleeding 2) Any abnormal vaginal bleeding 3) Pelvic pain dysuria, obstipation, low back pain
    25. 25. Cervical Carcinoma Pattern of Spread • Adjacent structures – Vagina – Para cervical tissues – Bladder and Rectum • Lymphatic spread Obturator Pelvic Common Iliac Para-aortic • Rarely hematogenous spread
    26. 26. Anatomy of the Pelvis URINARY BLADDER BLADDER PILLER VAGINA CARDINAL LIGAMENT RECTUM RECTAL PILLAR PREVESICAL SPACE RECTRORECTAL SPACEPARARECTAL SPACE PARAVESICAL SPACE VESICOVAGINAL SPACE RECTOVAGINAL SPACE
    27. 27. Cervical Carcinoma Treatment • Stage 1 and 2A: Surgery or Radiation therapySurgery or Radiation therapy – Radical Hysterectomy (Oophorectomy not necessary) – Pelvic Lymphadenectomy – Para-aortic lymph node biopsy – Upper vaginectomy
    28. 28. Cervical Carcinoma Treatment • Stage 1 and 2A: Surgery or Radiation therapySurgery or Radiation therapy • Stage 2B – 4: Chemotherapy and RadiationChemotherapy and Radiation – Cisplatinum 40mg/m2 – Whole pelvis radiation therapy • 180 cG daily to 5040 cG – Intracavitary radiation • inpatient 2 days, twice
    29. 29. Brachytherapy Intracavitary Tandem and Ovoids
    30. 30. Brachytherapy Interstitial Implant
    31. 31. Cervical Carcinoma Treatment Recurrence • Central Pelvic Recurrence – Total Pelvic Exenteration • en bloc removal of uterus, bladder, rectum, vagina • 30% survival • Regional or Distant Recurrence – Cisplatinum – based chemotherapy – Palliative only
    32. 32. Cervical Cancer Survival Curve Stage 1a1 (n=518) Stage 1a2 (n=384 Stage 1b (n=384) Stage 11a (n=813) Stage 11b (n=2551) Stage 111b (n=2350) Stage 111a (n=180) Stage 1Va (n=294) Stage 1Vb (n=198)

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