Altering Cervical Cancer s Trajectory. Mary S. Beattie, MD, MAS Medical Director, Women s Health BioOncology US Medical Affairs

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Altering Cervical Cancer s Trajectory Mary S. Beattie, MD, MAS Medical Director, Women s Health BioOncology US Medical Affairs

Objectives and Agenda Objectives: Appreciate cervical cancer (CC) burden Understand why cervical cancer is a model disease for screening Emphasize importance of cervical cancer screening, including potential missed opportunities and barriers Agenda Cervical cancer background and epidemiology HPV, CC natural history, prevention, and screening 2

Cervical cancer is the third most common cancer in women worldwide 1,2 In 2008, 530,000 new cases occurred globally, resulting in 275,000 deaths * Numbers indicate cases per 100,000 population 1. GLOBOCAN 2008. International Agency for Research on Cancer website. http://globocan.iarc.fr/ as of 5/13 2. Schiffman M, Castle PE. N Engl J Med 2005; 353:2101-2104 3

Cervical cancer epidemiology: US Increased Pap test usage has contributed to a 70% decrease in cervical cancer incidence since the 1950s Tends to develop in younger women Two-thirds of cases occur in women 54 years Median age at diagnosis: 49 years Relatively rare in US 21st most common cancer 12,360 new cases in 2014 (1.5% of all new diagnoses in women) 4020 deaths in 2014 (1.5% of all cancer deaths in women) Minority women have highest incidence and mortality rates Percent of New Cases Hispanic/Latino African-American American Indian/Alaska Native Age 4

HPV, necessary but not sufficient Human Papilloma Virus infection is common Over 75% of sexually active adults (by 50 y/o) have been exposed to HPV 1 Other potentially important predictors for cervical cancer are smoking and immunosupression Cervical cancer - model disease for which prevention and screening can have significant impact Cervical cancer characteristics Generally slow growth and progression Opportunities for intervention in pre-cancer Prevention HPV vaccine Screening Pap smears 1. Manhart LE et al. Sex Transm Dis 2006; 33(8) 502-508 5

Progression to cervical cancer Normal cells of the cervix gradually develop precancerous changes that can eventually evolve into cancer Precancerous changes can be detected with the Pap test Treating dysplasia can prevent most cervical cancers 6

Natural history of high-risk HPV infection and potential progression to cervical cancer 1 * * * Cervical squamous intraepithelial neoplasia 1. Reprinted from Pagliusi SR, Aguado Mt. Vaccine, 2004;23:569-578. Copyright 2004, with permission from Elsevier 7

Screening guidelines generally agreed points Pap screening should generally be started at 21 years old and performed every 3 years until age of 65 HPV co-testing, when used, should begin at 30 years old and should be performed every 5 years until age 65 All screening can be stopped in women after the age of 65, provided they have an adequate screening history Women who have had a hysterectomy with removal of cervix do not need to have cervical screening, unless the hysterectomy was done to treat a precancerous cervical lesion or cervical cancer References: American Cancer Society (ACS), American Society of Colposcopy and Cervical Pathology (ASCPP), and the American Society for Clinical Pathology (ASCP) The US Preventive Services Task Force (USPSTF) The American College of Obstetricians and Gynecologists (ACOG) 8

System failures are associated with Cervical Cancer in the US Most CC cases are in women who didn t get screening in the prior 3 years Most of these fail to screen had more than 3 visits to health care providers in the prior 3 years Fail%to%Follow)up% (N=106),%13%% No#Visits# (N=89),#19%# Fail%to%Detect% (N=263),%32%% Fail%to%Screen% (n=464),%56%% >3#Visits# (N=292),#63%# 102#Visits# (N=83),# 18%# References: 9

However, cervical screening may not detect all abnormalities Because screening may not detect all abnormalities, it does not always ensure early intervention 1,2 False-negative caused by sampling and detection errors 1 Adenocarcinoma difficult to detect by Pap smear 2 Some women with cervical cancer have had a recent normal Pap smear prior to diagnosis 3 Some women are nonadherent to cervical cancer screening 3 1. Nanda K, McCrory DC, Myers ER, et al. Ann Intern Med. 2000;132:810-819. 2. Johnston G, MacIsaac M, Rankin E. Available at: http://cancercare.ns.ca/media/documents/surveillance_info_system.pdf. Accessed February 4, 2005 3. Sung HY, Kearney KA, Miller M, Kinney W, Sawaya GF, Hiatt RA. Cancer. 2000;88:2283-2289 10

Summary Cervical cancer is largely preventable Screening barriers and missed opportunities deserve further study Eventually, research in this field could potentially lead to impactful interventions It takes a village 11

Appendix 12

Classification of cervical cancer by failures in screening, detection and follow-up 1 1. Leyden WA, Manos M, Geiger AM, et al. J Natl Cancer Inst. 2005;97:675-683. Reprinted with permission from Oxford Journals, Oxford University Press 13