Cervical cancer screening module 1
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Cervical Cancer Screening Module 1 - from Massachusetts Medical Society. ...

Cervical Cancer Screening Module 1 - from Massachusetts Medical Society.
Copyright © 2013. Massachusetts Medical Society, 860 Winter Street, Waltham Woods Corporate Center, Waltham, MA 02451-1411

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Cervical cancer screening module 1 Cervical cancer screening module 1 Presentation Transcript

  • Cervical Cancer Screening Navigating the Jungle Annekathryn Goodman, MD Division of Gynecologic Oncology Massachusetts General Hospital Harvard Medical School
  • Cervical Cancer Screening Module I Background Epidemiology Preinvasive disease Module I
  • Cervical Cancer Screening Background Cervical Cancer Statistics Rationale for screening The History of Screening The Consequences of Over-screening Module I
  • Background Cervical Cancer Statistics 2012 In the United States 12,170 women diagnosed with invasive cervical cancer In the United States, 4220 women died from cervical cancer USA: 6TH MOST COMMON CANCER BLACK AND LATINA WOMEN USA: 13TH MOST COMMON CANCER WHITES In contrast, cervical cancer is the third most common cancer with an estimated 530,000 new cases Module I
  • Cervical cancer Incidence among 6 Asian Ethnic Groups in the United States 1996-2004 Cancer 2010; 116:949-956 Vietnamese women 18.9 /100,000 Korean women 11.9/100,00 Asian Indian/ Pakistani women 4.5/100000 SCC rates increase with age in Vietnamese, Korean, Filipina, and Chinese women Module I
  • Background Cervical Cancer Statistics 2012 In contrast, cervical cancer is the third most common cancer with an estimated 530,000 new cases world - wide Module I
  • Cervical Cancer - Globocan 2008 Estimated numbers in thousands CASES DEATHS World 530 275 More developed regions 76 32 Less developed regions 453 242 Africa region 75 50 Americas region 80 36 Eastern Mediterranean 18 11 Europe 61 28 Western Pacific 105 46 South East Asia 188 102 USA 11 3 China 75 33 India 134 72 European Union 31 13 Module I
  • Background Rationale for Screening Cervical cancer has a long preinvasive phase There are effective and cheap screening tests for preinvasive and invasive cervical cancer Cervical cancer can be prevented with adequate screening Module I
  • Estimated annual contributions to squamous cervical cancer screening failures U.S. % Never screened >5 yrs since screened False Negative Pap Errors in follow up Total 50% 10% 30% 10% # women 6,280 1,260 3,770 1,260 100% 12,560 Sawaya Obstet Gynecol 1999 660,000 women aged 25-29 are invited for screening in England. 2005-06, only 69.4 per cent did so, - 80 per cent in 1995. A similar trend has been seen in women aged 30-34. Module I
  • The Papanicolaou Smear Dramatically decreased cervical cancer mortality Meta-analysis of 94 studies Sensitivity 30-87% Specificity 86 – 100% Obstet Gynecol 1995, 86:1017 Annals Intern Med 2000, 132:810 Risks Errors in sampling Errors in transfer of cells Errors in interpretation Errors in evaluation of abnormal results
  • Background The History of Screening 1941 Introduction of Papanicolau Smear Introduction of liquid based pap smear techniques (ThinPrep, SurePath) 1988 Bethesda System: standardization of terminology 2001 Revision of Bethesda System Module I
  • Background The History of Screening 2012 Lower Anogenital Squamous Terminology Project (LAST): changes in terminology for HPV associated lesions of lower genital tract Module I
  • Background The Consequences of Over-Screening Treatment of lesions that have a high probability of spontaneous regression Treatment of Teenagers Long Term Changes to Cervix Module I
  • The Consequences of Over-Screening Treatment of lesions that have a high probability of spontaneous regression 80 percent of low grade lesions will spontaneously regress 63 percent of CIN 2 lesions regress by three years Module I
  • The Consequences of Over-Screening Treatment of Teenagers Scarring of cervix Cervical stenosis Shortening of cervix Traumatic Dyspareunia Module I
  • The Consequences of Over-Screening Long Term Changes to Cervix Pain Cervical Stenosis Infertility Cervical Incompetence during pregnancy Inability to perform adequate screening Module I
  • The Consequences of Over-Screening Long Term Changes : CERVICAL STENOSIS
  • The Consequences of Over-Screening Long Term Changes: CERVICAL INCOMPETENCE LEEP Procedure and Preterm Birth one LEEP: 7.2% preterm deliveries ((between28 and 37 weeks) No LEEP: 4.6% Two LEEPs: preterm risk increases 3x Obstet Gynecol vol121:1063-1067, 2013 Module I
  • Cervical Cancer Screening Epidemiology Human Papillomavirus Infections Risk factors for cervical cancer Module I
  • HPV DEFINITIONS NON-ENVELOPED VIRUSES DOUBLE STRANDED, CLOSED CIRCULAR DNA GENOME - 8 KILOBASES 3 REGIONS TO GENOME 1- UPSTREAMN REGULATORY REGION - REGULATES TRANSCRIPTION AND REPLICATION 2- EARLY REGION: 6 OPEN READING FRAMES - E1, E2, E4, E5, E6, E7 3- LATE REGION: 2 ORFs - VIRAL STRUCTURAL PROTEINS L1, L2 Module I
  • HPV SUBTYPES - 45 mucosal/genital subtypes - high risk : HPV - 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58,59,66, 68 - low risk: HPV - 6, 11, 40, 42, 43, 44 Module I
  • HPV : VIRAL LIFE CYCLE INFECTION LIMITED TO EPITHELIAL CELLS COMPLETION OF LIFE CYCLE REQUIRES EPITHELIAL DIFFERENTIATION STRATIFIED SQUAMOUS EPITHELIUM: BASAL/PARBASAL, MIDZONE, SUPERFICIAL HPV INFECTS BASAL CELLS VIRAL SHEDDING FROM SUPERFICIAL LAYER Module I
  • VIRAL INDUCED ONCOGENESIS VIRUS DOES NOT COMPLETE NORMAL LIFE CYCLE INFECTION PERSISTS OVER TIME E6/E7 MEDIATED DEGRADATION OF P53 & RB1 VIRAL DNA MAY INTEGRATE INTO HOST GENOME INCREASED GENOMIC INSTABILITY GAIN OF CHR 3q IN CX CA METHYLATION OF HPV DNA Module I
  • % OF CANCERS ATTRIBUTABLE TO HPV CANCER SITE % HPV % HPV -16 & HPV-18 CERVIX 100 70 VAGINA 40 80 VULVA 40 80 PENIS 90 63 ANUS 90 92 ORAL CAVITY 25 95 OROPHARYNX 35 89 Module I
  • Epidemiology Human Papillomavirus Infections Almost all cases of cervical cancer are caused by Human Papillomavirus (HPV) infection However most HPV infections resolve within a few months to years Module I
  • HUMAN PAPILLOMAVIRUS TRANSMISSION € Sexual ( incubation period: 3 weeks to 8 months) € nonsexual (conjunctiva and nose) € vertical (mother - fetus) € laser plume Module I
  • Prevalence of High Risk HPV 25 20 15 10 5 0 15-19 20-24 25-29 30-34 Sellors JW CMAJ 2000;163(5) 35-39 40-44 45-49 Module I
  • Epidemiology Risk factors for Cervical Cancer Persistent high risk HPV infections is the main cause of cervical cancer Module I
  • RISK FACTORS - NEW PERSISTENT HIGH RISK HPV INFECTION LACK OF PAP SMEAR SCREENING OTHER UNKNOWN FACTORS http://jid.oxfordjournals.org/content/191/11/1808. full Module I
  • EPIDEMIOLOGY OF HPV PREVALENCE: 45 - 50% LIFETIME RISK: 79 – 85% ?100% Module I
  • Estimated Annual Incidence of Select HPV-Related Disease in the United States 9730 new cases of cervical cancer1 330,000 new cases of high-grade cervical dysplasia (CIN 2/3)2 1.4 million new cases of low-grade cervical dysplasia (CIN 1)2 Approximately 1 million new cases of genital warts3 1. American Cancer Society. Cancer Facts & Figures 2005. Atlanta, Ga: ACS; 2005:1−60. 2. Schiffman M, Solomon D. Arch Pathol Lab Med. 2003;127:946–949. 3. Fleischer AB, Parrish CA, Glenn R, Feldman SR. Sex Transm Dis. 2001;28:643–647.
  • AGE SPECIFIC RATES OF HPV + HR WITH NORMAL CYTOLOGY Bansal et al Gyn Onc 115:257; 2009 Age group Total # tested # positive for hr HPV % positive 10-19 162 13 8 20-29 1137 92 8 30-39 6898 190 3 40-49 8137 135 1.6 50-59 7026 112 4 60-69 2584 39 1.5 70-79 522 10 2 >80 92 4 4
  • RISK FACTORS (OLD) MULTIPLE SEXUAL PARTNERS EARLY AGE OF FIRST INTERCOURSE POVERTY HORMONAL ENVIRONMENT (OCP USE?) TOBACCO USE IMMUNE SUPPRESSION HIGH RISK MALE PARTNER LACK OF PAP SMEAR
  • CERVIX GREATEST NEOPLASTIC DANGER HORMONAL MILEAU? MATURATION CHANGES (SQUAMOUS METAPLASIA?) TRAUMA? COFACTORS? Module I
  • Cervical Cancer Screening Preinvasive Disease Terminology Review of Lower Genital Tract Anatomy Natural History Module I
  • Preinvasive Disease Terminology Preinvasive disease is defined as atypical or neoplastic changes Old terminology : dysplasia Current Terminology: Intraepithelial neoplasia Module II
  • Preinvasive Disease Terminology (see also Module II) dysplasia Intraepithelial neoplasia definitions Terminology by area of lower gential tract mild I Lower 1/3 of epithelium is dysplastic CIN: cervical intraepithelial neoplasia moderate II Lower 2/3 is dysplastic VAIN: vaginal severe III Full thickness dysplasitc change VIN: vulvar Full thickness dysplastic change AIN: anal Carcinoma in situ CIS PIN: penile Module I
  • Preinvasive Disease Review of Lower Genital tract Anatomy Stratified squamous epithelium lines the vagina and exocervix The endocervix is lined by columnar glandular epithelium The boundary between the squamous and columnar epithelium is called the squamocolumnar junction. (SCJ) The SCJ migrates from far out on the exocervix to the endocervical canal over a woman’s lifetime. The boundary between the old SCJ and the current SCJ is called the transition zone Module I
  • Preinvasive Disease Review of Lower Genital Tract Anatomy Module I
  • Preinvasive Disease Natural History Module I
  • HPV(HIGH RISK) NATURAL HISTORY 3-8 MONTH INCUBATION PERIOD 80% CLEARED IN 12 MONTHS 95% CLEARED BY THREE YEARS LESS THAN 1% OF ALL HPV HIGH RISK INFECTIONS LEAD TO INVASIVE CANCER Module I
  • Natural History of HPV Infections Wright and Schiffman (2003) NEJM Module I
  • Natural History of HPV in Young Women RESULTS • cumulative risk of HPV was 44% • HPV 16 most common subtype • 28/2011 developed HSIL greatest risk for HSIL was 6-12 months after detection of HPV 16 (Lancet 2001; 357:1831) Module I
  • CERVICAL CANCER SCREENING MODULE I CONCLUSIONS -Cervical cancer risk varies around the world. There are disparities in risk within the United States. -HPV infection is associated with all cervical neoplasia and the majority of lower genital tract neoplasia. -The natural history of most HPV infections: resolution within three years.