Division of STD Prevention, CDC Surveillance for Human Papillomavirus Associated Vaccine Preventable Diseases Current State of Activities and Future Directions Deblina Datta, MD Division of STD Prevention, CDC NIC 2007 Kansas City, MO

>100 HPV types Cutaneous Sexually transmitted (~40 types) “high-risk” (HR) types “Common” oncogenic (16,18) warts “low-risk” (LR) types (hands/feet) non-oncogenic (6,11) This is another graphic showing the 40 or so sexually transmitted types in green broken into high risk, or oncogenic types in blue and low risk, or non-oncogenic [emphasize non cancer causing] types in yellow. Genital infection with the high risk types can lead to anogenital cancers, including cervical cancer. It can also lead to low grade and high grade cervical abnormalities which are detected on pap smears. I will discuss these abnormalities later in the presentation. Genital infection with low risk HPV types can lead to low grade cervical abnormalities, genital warts, and a rare condition of children born to mothers with genital warts, called recurrent respiratory papillomatosis. I will not discuss the HPV types involved in cutaneous infections in this presentation. low grade cervical abnormalities high grade abnormalities (cancer precursors) anogenital cancers low grade cervical abnormalities genital warts respiratory papillomatosis

Cancers Attributable to HR HPV Infection, U.S., 2002 Site Total Cancers* % Estimated HPV Attributable Fraction+ Cervix 12,085 100 Anus 3,703 85 Vulva/Vagina 4,480 40 Penis 985 Oral/Pharyngeal 10,088 15 As mentioned, HR-HPV infection can lead to development of different anogenital cancers such as cervical, anal, vulvar, vaginal and penile cancers. There is also evidence implicating HR-HPV infection in a subset oral/pharyngeal cancers. This slides shows the US burden of cancers due to HR-HPV for 2002 as well as the percentage estimated attributable fraction due to HR-HPV. Virtually all cervical cancers are due to HR-HPV, less in other anogenital cancers and only a subset of oral/pharyngeal cancers. As you see, of the list, cervical cancer is the most important. *2002 US Cancer Statistics, CDC/NCI, 2005 +Parkin M. International Papillomavirus Conference, Vancouver, Canada, 2005/Trotter H, Franco E, Vaccine; 2006 in press

Estimated Annual Abnormal Pap Tests, U.S. CA 15,000 HSIL 300,000 LSIL 1,000,000 Pap tests help to identify women with these CIN precursor lesions before they develop into cancer. Approximately 50 million Pap tests are performed each year and of those 2 mil will display lesions of unknown significance, or ASCUS, 1 mil will have low grade abnormalities and 300,000 will display high grade abnormalities. Women with these abnormalities will require further follow-up or care, however even if untreated, only a few will go to develop cervical cancer. The cateogory of ASCUS, or abnormalities of unknown significance, is large and requires many resources to follow up these women. ASC-US 2,000,000 Modified from Hildesheim, A., National Cancer Institute

Natural History of HPV Infection and Cervical Cancer 1 year Up to 5 years Up to 20 years Persistent infection CIN* 2/3 Initial HPV infection CANCER CIN* 1 CLEARED HPV INFECTION *cervical intraepithelial neoplasia

4% 6% 90% In this country, as opposed to developing countries, most of the HPV related costs are due to care of women with abnormal Pap tests. Small proportions, 4 and 6% are spent on cervical cancer and anogenital warts, respectively. Modified from Chesson et al. Perspectives on Sexual and Reproductive Health 2004, 36(1): 11-19)

HPV-Related Disease Burden, U.S. Cervical cancer: 9,710 cases & 3,700 deaths (2006 estimate) 70% caused by types 16,18 Pap tests: 50 million; 2.8 million abnormal Precancerous lesions Genital warts: .5 to 1 million 90% caused by types 6,11 Recurrent respiratory papillomatosis (rare) Other anogenital cancers: (anal, penile, vaginal, vulvar) This slide gives a more complete picture of HPV-related disease burden and resources, including diseases from HR as well as LR HPV. The list includes cervical cancer, the 50 million Pap tests (of approximately which 2.8 million are abnormal and may require follow up care), approximately 500,000 to 1 million cases of genital warts, recurrent respiratory papillomatosis, and other anogenital cancers.

Quadrivalent HPV Vaccine FDA Licensure – June 8, 2006 Indicated in girls and women 9-26 years of age for the prevention of the following diseases caused by HPV types 6, 11, 16, and 18: Cervical cancer Genital warts (condyloma acuminata) Cervical, vaginal and vulvar precancerous or dysplastic lesions

Routine Vaccination Provisional Recommendation ACIP recommends routine vaccination of females 11-12 years of age with three doses of quadrivalent HPV vaccine The vaccination series can be started as young as 9 years of age

Females 13-26 Years Provisional Recommendation At the beginning of the vaccination program, there will be females older than 12 years who could benefit from HPV vaccine Vaccination is recommended for females 13-26 years of age who have not been previously vaccinated Ideally vaccine should be administered before onset of sexual activity, but females who are sexually active should still be vaccinated

Challenges for HPV Surveillance HPV not nationally reportable HPV testing not routinely performed, not necessarily associated with disease Clinical endpoints not reportable (except cancers) Clinical endpoints related to HPV infection separated by years/decades from initial infection Precancerous lesions Cancers

HPV Testing Clinical test Research test Digene Hybrid Capture 2 (Gaithersburg, MD) Adjunctive to Pap testing in certain circumstances (i.e. not all women receive this) Research test HPV typing (PCR) Serology

Current Surveillance Systems National Program of Cancer Registries/SEER National network of cancer registries funded by CDC (NPCR) and NIH/NCI (SEER) Comprehensive source for cancer statistics in the US

Cancer Surveillance

Current Surveillance Systems NHANES HPV prevalence in a representative sample of US civilian non-institutionalized population PCR based HPV prevalence estimates (type data available) Limited in that estimates based on small sample of individuals extrapolated to US population

Other Possible Endpoints for Surveillance Genital warts Sentinel network of STD clinics Abnormal pap tests/referrals for biopsy Title X clinics (2.5 mil pap tests/yr) Abnormal cervical biopsy/precancerous lesions CIN 2, CIN 3 Expanding cancer registries All of these endpoints Administrative datasets (Medstat, VSD)

CDC’s Current Recommendations on HPV Associated Surveillance Activities No routine surveillance data collection at this time (except for those already being collected via cancer registries) CDC considering feasibility of surveillance for more proximal measures of HPV associated disease CDC currently recommends state and local HD’s to Educate providers about the link between HPV and cervical cancer Education for providers and the public about the availability of the HPV vaccine Emphasize the ongoing importance of regular cervical screening (Pap tests) despite the availability of HPV vaccine

Acknowledgements Division of STD Prevention Lauri Markowitz Eileen Dunne Division of Cancer Prevention Mona Saraiya Herschel Lawson