New Screening Guidelines for the Female Patient

Cathy Callahan, MD MPH FACOG Associate Professor Virginia College of Osteopathic Medicine

Objectives

• • • Cite scientific evidence to support the revised clinical guidelines for Pap smears and mammography. Apply the current recommendations for screening and for follow-up of abnormal findings.

Identify resources for guidelines for clinical questions regarding screening tests.

Henrietta Lacks 1920-1951

• • • • Born Loretta Pleasant in Roanoke, VA Had 5 children Last child was born 4 ½ months before cervical cancer diagnosis Feb 1, 1951: seen at John Hopkins University for painful “knot” in her cervix and vaginal bleeding by Dr. Howard Jones

The Immortal Life of Henrietta Lacks by Rebecca Skloot

HeLa Cell Line

• • • • Dr. George Gey grew the cells (without her knowledge as was usual at the time) and grew them Became immortal-the first cell line sold to others

Unwitting Heroine of Modern Medical Science

▫ Jonas Salk for polio vaccine in 50’s ▫ HIV research ▫ Effects of radiation ▫ Gene mapping ▫ Countless other scientific pursuits Family got calls in 1970s for blood and learned of this for the first time.

The Pap

(aka the greatest cancer screening success story of all time!) • • 1941 Dr. George Nicholas Papanicolaou publishes

“Diagnostic value of vaginal smears in

carcinoma of the uterus” AJOG Mortality rates for cervical cancer and uterine cancer declined 82% from 1931-2004

Since the Pap

• • • • 1998 Bethesda system ▫ Introduced 1998 ▫ 2001 classification of the abnormal Pap introduced 2000 FDA approved test for Human Papillom0virus DNA 2006 ASCCP Consensus Guidelines (American Society for Cervical Cytology and Pathology ) 2006 FDA approves Gardasil, quadravailent HPV vaccine ▫ HPV16 and 18 associated with 70% of cervical cancers ▫ HPV 6 and 11 associated with 90% of genital warts Stagg Elliott V. Dr. Pap’s smear; The test and its times. American Medical Association NewsAccessed on 9/15/2011; http://www.ama-assn.org/amednews/2007/09/03/hlsa0903.htm

Cervical Cytology

• NETHCON (Netherlands ThinPrep vs Conventional Cytology) 2009 “Liquid-based cytology does not perform better than conventional Pap tests in terms of relative sensitivity and PPV for detection of cervical cancer precursors. “

Advantages of liquid methods

Decreased inadequate samples • HPV testing • Gonorrhea and Chlamydia testing

Advantages of traditional

Cost: $25-$40 vs. $45-$60 Siebers AG et al. Comparison of Liquid-based Cytology with Conventional Cytology for detection of cervical cancer JAMA: JAMA. 2009;302:1757-1764.

The Cervical Transformation Zone

• Area of immature metaplasia between the original and current squamocolumnar junction (SCJ) 1 • ~99% of HPV-related genital cancers arise within the transformation zone of the cervix.

1 • The Pap test is used to obtain cells from the cervix (primarily transformation zone) for cervical cytology screening.

2 1. Castle PE.

J Low Genit Tract Dis.

2004;8:224 –230. 2. American Cancer Society. Prevention and early detection. Pap test. July 2006; Available at; http://www.cancer.org/docroot/PED/content/PED_2_3X_Pap_Test.asp?sitearea=PED

The Cervical Transformation Zone

Endocervical cells

Classification Terminology for Cervical Cytology: The 2001 Bethesda System

Normal 1 ASCUS 2 LSIL 3 HSIL 3

• • Two types of atypical squamous cells (ASC) (ASCUS) ▫ Atypical squamous cells, cannot exclude high 4 ▫ Atypical squamous cells of undetermined significance grade squamous intraepithelial lesions (ASC H) Squamous intraepithelial lesions (SIL) 4 ▫ Low ▫ High grade SIL (LSIL): Mild dysplasia, cervical intraepithelial neoplasia 1 (CIN 1) grade SIL (HSIL): Moderate and severe dysplasia, CIN 2/3, carcinoma in situ (CIS) 1. Spitzer M, Johnson C. Philadelphia, Pa: WB Saunders Company; 2002:41–72. 2. Apgar BS, Zoschnick L. Am Fam Physician. 2003;68:1992–1998. 3. Cannistra SA, Niloff JM. N Engl J Med. 1996;334:1030–1038. 4. Solomon D, Davey D, Kurman R, et al, for the Forum Group Members and the Bethesda 2001 Workshop. JAMA. 2002;287:2114–2119.

www.olah.co.uk/cervicalsmears.htm

HPV

Infects 6 million in the US annually Non-enveloped double stranded DNA virus 1  • • • >100 types identified 30–40 anogenital 15–20 oncogenic (16, 18, 31, 45) ▫ HPV 16 (54%) and 18 (13%), 31 and 45 account for 80% of worldwide cervical cancers Non-carcinogenic HPV:  HPV 6 and 11 are most often associated with external genital warts (~90% of cases) 1. Howley PM. In: Fields BN, Knipe DM, Howley PM, eds. Philadelphia, Pa: Lippincott 5. Clifford GM, Smith JS, Aguado T, Franceschi S. Br J Cancer. 2003:89;101–105. Raven; 1996:2045–2076.

2. Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930–934. 3. Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis. 2002;35(suppl 2):S210–S224. 4. Muñoz N, Bosch FX, de Sanjosé S, et al. N Engl J Med. 2003;348:518–527.

HPV (or The Common Cold of Sex)

Lifetime likelihood of getting genital HPV to be in the range of 75-90% 1 Infection From Time of First Sexual Intercourse 2

Study of female college students (N=603) 1 0.8

0.6

0.4

0.2

0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 Months Since First Intercourse

1.

2.

ASCCP accessed on September 14, 2011 http://www.asccp.org/PracticeManagement/HPV/NaturalHistoryofHPV/tabid/5962/Default.asp

From Winer RL, Lee S-K, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human Papillomavirus infection: incidence and risk factors in a cohort of female university students.

Am J Epidemiol.

2003;157:218 –226.

Natural history of HPV

• • • • • Genital skin-to-skin contact (Intercourse not required) Condoms only partially protective Risk of acquiring genital warts after one episode ~65% 64-70% of male partners of women with cervical HPV disease will have HPV penile lesions on exam Time from exposure to HPV to development of genital warts is 4 weeks to 8 months 90% of patients who test positive for HPV become HPV negative within 6 to 24 months ▫ Not known if the HPV is latent or the virus is actually eliminated ASCCP accessed on September 14, 2011 http://www.asccp.org/PracticeManagement/HPV/NaturalHistoryofHPV/tabid/5962/Default.aspx

New guidelines based on natural history of HPV

• • • • • HPV is a requirement for most cancers 1 HPV usually regresses in young women The additional sensitivity of HPV testing compared with cytology could permit extended cervical screening intervals2 (6 year intervals if HPV testing replaces cytology!) Takes 1-8 years (maybe longer)for the progression to cancer HPV more likely to persist in: ▫ Immunocompromised ▫ Smokers ▫ OCP users ▫ Women over 30 1. ASSCP. www.assccp.org

2. 2.Kitchener HC. ARTISTIC: a randomised trial of human papillomavirus (HPV) testing in primary cervical screening .

Health Technology Assessment 2009; Vol. 13: No. 51

Screening guidelines Initial Pap smear

• • At age 21 (ACOG) At age 21 or with-in 3 years of beginning sexual intercourse ▫ ASCCP

(Amer Society for Colposcopy and Cervical Pathology)

▫ ACS

(American Cancer Society)

▫ USPSTF

(United States Preventive Services Task Force)

How often should I have a Pap smear?

Age ACS ACOG USPSTF

Every two years Every three years

21 to 29 Over 30

Screening guidelines: Take home message (But stay tuned!!!)

First Pap ▫ Age 21 ( or 3 yrs after initiating sex) Interval: ▫ <30: Every two years ▫ >30: Every three years (with at least 3 consecutive negative Paps) Annually screen high risk patients ▫ in utero DES exposure ▫ immunocompromised ▫ a history of CIN II/III Stop screening ▫ Age 75 ▫ Post hysterectomy (benign indication) without prior abnormal Pap

Prognosis (With-in 2 years)

CIN I ~ 3% of specimens ~76% HPV HR + Regress 70-90% Persist Progress 13%

* 70-80% in adult women, 90% regression in adolescents and young women

2006 Consensus Guidelines for the Management of Women with Abnormal

Cervical Cancer Screening Tests were published in the American Journal of Obstetrics and Gynecology (2007;197(4):346-355).

www.asccp.org

American Society for Colposcopy and Cervical Cytology

Prognosis (With-in 2 years)

CIN II-III ~ .7% of specimens 2% have invasive cancer Regress ~30% Persist Progress 12-36%

2006 Consensus Guidelines for the Management of Women with Abnormal

Cervical Cancer Screening Tests were published in the American Journal of Obstetrics and Gynecology (2007;197(4):346-355).

Cervical Cancer Vaccines

3 doses over 6 months , ~130.00/ dose retail • Gardasil: (Merck, )  Quadrivalent HPV Vaccine ▫ Females and males ages 9 to 26 years for the prevention of the following diseases caused by HPV Types 6, 11, 16, and 18 Cervical cancer and dysplasia   Vulvar dysplasia Genital warts (condyloma acuminata) • Cervarix: (GlaxoSmithKline, 8/2009) Bivalent Vaccine ▫ Females only ages 9 through 25 years for the prevention of diseases caused by HPV Types 16 and 18 • CDC continues to recommend vaccination against HPV after reviewing reports of reports of adverse events 1 1. Reports of Health Concerns Following HPV Vaccinationhttp://www.cdc.gov/vaccinesafety/vaccines/hpv/gardasil.html

Breast Cancer Screening

Breast Cancer Epidemiology 2011

• • • • 232, 060 estimated new cases of breast cancer 1 Second most common cause of cancer deaths Breast cancer deaths: ↓ 1/3 in last 25 years Self-breast exam and CBE do not uniformly show reduction in mortality 2 1. American Cancer Society, Inc, Surveillance Research. Cancer Facts and Figures 2011 2. Griffin JL, Pearlman; Breast cancer screening in women at average risk and high risk. Obstet Gynecol 2010(Dec);116(6):1410-21 (PMID 21099612)

New York Times ,

November 16, 2009 • Panel Urges Mammograms at 50, Not 40 • New Guidelines on Breast Cancer Draw Opposition “

Many women are confused about new federal recommendations to scale back routine breast cancer screening.”

• Screening Policy Won’t Change, U.S. Officials Say (Nov 18, 2009)

“ The Obama administration distanced itself Wednesday from new standards on breast cancer screening that were recommended this week by a federally appointed task force, saying government insurance programs would continue to cover routine mammograms for women starting at age 40.”

Harms to screening???

▫ ▫ ▫ ▫ ▫ ▫ Public cost “ number needed to invite for screening to extend one woman's life" as 1904 for women aged 40 to 49 years and 1339 for women aged 50 to 59 years”1 Psychological Unnecessary imaging tests Unnecessary biopsies Radiation exposure Over diagnosis (treating a cancer that might not ever become clinically apparent)

1.http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanrs.htm

USPSTF accessed on 9-15-2011.

2.Nelson, HD et al. Screening for Breast Cancer: An Update for the USPSTF. Ann Intern Med. 2009;151:727-737.

USPSTF ACS ACOG

Screening Guidelines

Begin

50 40 40-49 50

Interval

2 years 1 year 1- 2 years 1 year

Stop

75 Ø Ø  The USPSTF revised recommendations in Nov 2009.

 Screening age 50-69: Mortality by 17%  Screening age 40-49 : Mortality by 3% Would you stop screening women younger than 50??

Rosenberg MA. Competing risks to breast cancer mortality. J Natl Cancer Inst Monogr 2006:15-9. [PMID: 17032889] Cronin KA, Feuer EJ, Clarke LD, Plevritis SK. Impact of adjuvant therapy and mammography on U.S. mortality from 1975 to 2000: comparison of mortality results from the CISNET breast cancer base case analysis. J Natl Cancer Inst Monogr 2006:112-. [PMID: 17032901]

Breast Cancer Screening

• 2009 USPSTF revised recommendations, Not universally endorsed: ▫ American Cancer Society ▫ American College of Surgeons ▫ American College of Radiology ▫ American College of Obstetricians and Gynecologists ▫ National Comprehensive Cancer Network • All 50 states require insurance coverage for screening programs • Medicare provides mammography coverage • The National Committee on Quality Assurance lists mammographic screening for breast cancer as one of its principal measures of quality of care

Digital Mammography

Disclaimer: Image taken from website of imaging center promoting digital mammography www.hastingsimagingcenter.com

USPSTF: • Overall detection is similar for women >50 • Age < 50 or women with dense breast tissue, overall detection is higher • Unclear if increased detection leads to reduced mortality • COST: 1.5 to 4x greater

Underserved women

• • • Every Women’s Life (Sponsored by VDH) ▫ http://www.vahealth.org/ewl/ Free Clinic System ▫ http://www.vafreeclinics.org/ Federally Qualified Health Centers ▫ http://www.vacommunityhealth.org/

Questions??

• Thank you to the Virginia Osteopathic Medical Association for the opportunity to discuss screening in women’s health