RECENT ADVANCES IN CERVICAL CANCER SCREENING

1. RECENT ADVANCES IN CERVICAL CANCER SCREENING Dr. Anurag Bansal M.D Associate Director – Medical Quest Diagnostics India Pvt Ltd Gurgaon

2. Cervical Cancer Disease progression HPVInfection 20% HPV persistence 80% Viral clearance HR- HPV Regression – symptomatic or asymptomatic Progression towards precancerous lesion Cancerous lesion Confidential – Do not copy or distribute

3. Why Cervical Screening? • One of the cancer types, which is treatable based on early Diagnosis • Relatively easy sampling • Disease has a long history; ~10 yrs. To reach cancerous stage • Conservative treatment for precursor lesions are feasible

4. American Cancer Society Guidelines forEarly Detection of Cervical Cancer • Cervical cancer screening should begin at age 21.Women between ages 21 and 29 should have a cervical cytology every 3 years. • Women between the ages of 30 and 65 should have a cervical cytology plus an HPV test (called “co-testing”) every 5 years. This is the preferred approach, but it is also OK to have a cervical cytology alone every 3 years. • Women over age 65 who have had regular cervical cancer testing with normal results should not be tested for cervical cancer. Once testing is stopped, it should not be started again. • Women who have been Vaccinated against HPV should still follow the screening recommendations for her age group. • Women who has had her uterus removed (and also her cervix) for reasons not related to cervical cancer and who has no history of cervical cancer or pre-cancer should not be tested.

5. There has been a sharp dip in cervical cancer incidence, across the world, in the last 2 decades Confidential – Do not copy or distribute

6. The National Screening Programme of NHS UK has resulted in 50% reduction in death rate • NHS Cervical Screening Programme started in 1988 • Every woman 20-64 years is screened for cervical cancer • Call-recall every 3-5 years Confidential – Do not copy or distribute

7. Tools available for Cervical Cancer screening - Cytology Conventional PAP smears: • 1940: Papanicolou exfoliated cervical cells on a glass slide; is the foundations of early cervical cancer screening. • The conventional PAP smear has been the most successful screening test, screening every 3-5years has resulted in a 70% reduction in incidence. Limitations: • False Negative Rate of up to 55%1 • Ambiguous reports of 6.4%2 • Inadequate specimens of 9.7% 2 1. Hutchinson et al., AJCP, Vol 101-2; 215-219, 2. DOH Statistical Bulletin 2000/2001

8. Tools available for Cervical Cancer screening - Cytology Liquid Based Cytology • It is a liquid-based cytology evaluation that employs a fluid transport medium to preserve the cells and increase the stability. • The smear is clearer, easier to read, and minimizes obscuring blood, mucus, and non-diagnostic debris, resulting in increased accuracy. • The LBC have reduced the number of false negatives and the incidence of invasive cancer • Since its introduction, it has contributed to a further 28% reduction in invasive cervical cancers in the United States.1 1. Surveillance, Epidemiology, and End Results (SEER) Program. SEER Database: Incidence – SEER 9 Regs Public-Use, Nov. 2004 Sub (1973-2002), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2005, based on November 2004 submission

9. What we see under the microscope with Conventional PAP smear vs. LBC Conventional PAP Liquid Based Cytology Confidential – Do not copy or distribute

10. Tools available for Cervical Cancer screening HPV DNA testing – Invader Technology • This is a DNA based testing which utilizes the same sample type collected for liquid based cytology • The tests most commonly used to screen for HPV only detect those types that have a higher risk of progressing to cancer, like 16, 18, 31, 33, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 73 • Study results provide the strongest evidence to date in favor of using this test in national screening programs. The trial is published Online First in The Lancet Oncology. Limitations : • The current high-risk HPV DNA testing methods provide adequate sensitivity but, specificity is lacking.

11. Latest tool available for Cervical Cancer screening HPV RNA testing • HPV RNA based test determines the presence of E6/E7 mRNA from 14 high-risk HPV genotypes. • The sensitivity and specificity of this test were shown to be >92% and 99%, respectively, for detection of high-risk HPV types and 91% and >55%, respectively, for the detection of CIN2+. • In women undergoing routine screening (N=1,373), the sensitivity and specificity for the detection of CIN2+ were 100% and 88.3%, respectively.

12. Quest Diagnostics Cervical Screening- Data Thin Prep-LBC • Time period: Jan 2012-October 2013 • Total no of cases screened: 9614 • No. of positives: 181 • Percentage positivity: 1.9% HPV High Risk DNA Test • Time period: Jan 2012-October 2013 • Total no of cases screened: 3771 • No. of positives: 479 • Percentage positivity: 12.7% Confidential – Do not copy or distribute

13. Barriers Must be Overcome To Successfully Decrease Cervical Cancer • Access: Healthcare/Cervical Screening facilities should be available at the primary health care center level with trained staff availability to collect the samples and send it for further examination • Education: Many women are unaware of the value of early detection and treatment (and cure!) of cervical cancer. Men are often unaware of their role in transmitting disease. • Cost: Pap and/or HPV to be made accessible to larger masses by devising a mechanism to make it relatively less expensive. Confidential – Do not copy or distribute

14. Thank You