Infection as a non-communicable disease: A cervical cancer prevention primer Brighter Future Today: Advocacy for HPV and Cervical Cancer Prevention Across the Life Course USAID Global Health Mini-University 2017 September 14, 2017 Mary Carol Jennings, MD, MPH, Assistant Scientist Johns Hopkins Bloomberg School of Public Health International Health Department International Vaccine Access Center (IVAC)
Learning objectives By the end of this primer presentation, participants will be able to: 1. Give examples of primary, secondary and tertiary prevention; 2. Describe three ways in which cervical cancer, classified as a noncommunicable disease (NCD), can be prevented through approaches not typically applied to NCDs
Fill in the blank on burden: In low and middle income countries, cervical cancer is the # cause of cancer deaths in women. 1 (or 2) WHO. 2012 Global Cancer Estimates.
85% of the global cervical cancer burden is in low and middle income countries.
Infant delivers Infant and immune system mature Child becomes adolescent girl HPV Persists Why 9-14? 1 CIN1, 2, 3, Cancer WHO HPV Position Paper 2017
Successful Primary Prevention? Incidence: # cases unit time Examples? Vaccination Early exclusive breastfeeding Case endpoint: HPV infection, CIN, Cancer ; Death, stunting, pneumonia, diarrhea, etc. Hensrud (2000)
Successful Secondary Prevention? Incidence: # cases unit time Examples? Pap / VIA Mammography Case endpoint: (No disease) : CIN : Cancer ; (No cancer) : Cancer Short term increase long term bend in CVX CA curve Hensrud (2000)
Successful Tertiary Prevention? Incidence: # cases unit time Examples? Debulk / Radiation Case endpoint: Remission: Death Correct Indicator? 5-year Survival, or Case Fatality Rate >> Incidence Hensrud (2000)
Modes of cervical cancer prevention? Jhpiego / 2016 HPV Vaccines Risk Factor Reduction VIA / Cryotherapy / HPV Testing Bivalent 16, 18, GSK Quadrivalent, 16, 18, 6, 11, Merck 9-valent, 16, 18, 6, 11, 31, 33, 45, 52, 58, Merck (Cervarix, Gardasil, Gardasil-9) Primary Secondary Primary Non-typical for an NCD? Cryotherapy photo credit: Jhpiego. Cervical Cancer Prevention in Low Resource Settings. 2016.
Q: Which HPV types are high risk? A: 16, 18 Globally the two most common types, cause ~70% of cervical cancer 1 45 (6%) 31 (4%) 33 (4%) 35, 51, 52, 58, 59 2 These other hr-types are the next most prevalent globally 6 & 11? 1 National Cancer Institute https://www.cancer.gov/research/progress/250-years-milestones; 2 Bychkovsky 2016
Slide: Pollard. WHO-SAGE meeting on HPV, October 2016. * *6 & 11 do not have a cancer impact Globally most prevalent types = vaccine types
Potential for cross-protection (hr-hpv types) De Vincenzo Gynecol Oncol 2013; Wheeler Lancet Oncol 2012
Did we learn anything? By the end of this primer presentation, participants will be able to: 1. Give examples of primary, secondary and tertiary prevention; 2. Describe three ways in which cervical cancer, classified as a noncommunicable disease (NCD), can be prevented through approaches not typically applied to NCDs Difference: definitive prevention Similarity: delivery and technology
Reference Slides
Slide: Dr. Ike Obguanu, WHO. SAGE HPV Update October 2016.
HPV Modeling: Materials for SAGE meeting on HPV, October 2016. Modelled in HPV-ADVISE INDIA study. Modeled reduction of HPV 16/18 prevalence in women in LMIC over time since vaccination Vaccinate a multi-age cohort
Program Success 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 Coverage HPV prevalence Pre-cancer Cervical cancer
What does WHO say? (Through SAGE) Safe. Effective. Use for girls aged 9-14. Schedule Females <15 years at the time of first dose: a 2-dose schedule (0, 6 months) is recommended. If the interval between doses is shorter than 5 months, then a third dose should be given at least 6 months after the first dose. Females 15 years at the time of first dose: a 3-dose schedule (0, 1-2, 6 months) is recommended. WHO. HPV. February 2017; SAGE meeting October 2016.
A decade of introduction: Lessons Learned and Issues defined Brighter Future Today: Advocacy for HPV and Cervical Cancer Prevention Across the Life Course USAID Global Health Mini-University 2017 Julie Wieland, MPH Program Associate September 14, 2017
Learning Objectives By the end of this presentation, participants will be able to: Discuss issues and lessons learned in secondary prevention strategies and barriers to scaling best practices Share approaches with new technologies, HPV-DNA testing and treatment options, including thermal coagulation
Cervical Cancer Prevention Pathway Prevention Screening Visualization HPV vaccine Visual Inspection with Acetic Acid (VIA) Pap Test HPV diagnostics Visual inspection of the cervix with colposcopy Treatment of cervical dysplasia Cryotherapy Cold (hot) coagulation LEEP Cold knife cone (where LEEP is not available) Follow up HPV diagnostics Visualization
Secondary Prevention: Screening Three Options for screening women: 1. Pap test (cytology): Thin scrape of cells; reviewed for abnormalities 2. HPV diagnostic test: Uses DNA, mrna or biomarkers to identify presence of HPV virus; most tests cannot tell advancement towards cancer. Very accurate, too expensive. 3. Visual Inspection with Acetic Acid (VIA): Vinegar is applied to the cervix, wait 3-5 minutes, shine a light and look for white lesions. Cheap, but labor-intensive and moderately accurate. Treatment: Currently cryotherapy is recommended under the WHO Cervical Cancer Guidelines that were published in 2015 What secondary prevention method would you use for lowresource settings? Screening should be done at least once, preferably twice, for women ages 30-49. HIV+ women should be screened more frequently
Pros and cons of screening methods Pap Test: High specificity High negative predictive value VIA: High sensitivity Inexpensive at $10 Can be performed by any health worker HPV-DNA high specificity and sensitivity, especially to high-grade lesions Options for self-sampling Pap Test Requires lab and pathologist No single visit approach Can be costly at $24 Difficult to scale VIA acceptable specificity Acceptable negative predictive value Can be labor intensive Difficult to scale HPV-DNA Expensive at $5 to $15 per test Low sensitivity to low-grade lesions
The Single Visit Approach Cryotherapy Involves freezing of precancerous cervical cells usually with use of CO 2 LEEP Loop Electrosurgical Excision Procedure. A small wire loop is used to remove abnormal cells from the cervix. Issues: supply chain, lack of trained providers, distance to travel
Current Screen and Treat of Precancerous Lesions with Cryotherapy Cryo probe Often completed in 2 sessions: freezing for approximately three minutes, thawing of the cervix, and a second application of cryotherapy for three more minutes. Uses either nitrous oxide or carbon dioxide to freeze and destroy precancerous tissue
Issues related to treatment methods Supply chain concerns Delivery system within county Infrastructure issues within country Lack of trained personnel
Global Progress in Visual Inspection (VIA) for Cervical Cancer Screening National Program Pilot Program No Program "Global Progress in Visual Inspection (VIA) for Cervical Cancer Screening." Cervical Cancer Action. N.p., n.d. Status November 2016. Accessed Web. 1 May 2017.
The status quo is not getting us where we want to be Status quo is not getting us where we want to be What can we do about it?
Integrating Cervical Cancer Services with Other Services Youth-friendly primary care and SRH services HPV vaccination HIV and family planning services screen-and-treat Cervical cancer screen-andtreat programs counseling and testing for HIV and other STIs
New diagnostic technology The two tests currently available for scale-up are in the laboratory evaluation stage (near final phase) of prequalification by WHO. GeneXpert: $10 to $15 per test Non-batch, cartridge HPV-DNA testing Currently widely used in PEPFAR countries for multi-drug resistant tuberculosis testing CareHPV: Non-batch, cartridge HPV-DNA testing Batch test, meaning that 90 specimens are required to run the test. GeneXpert (Cepheid) CareHPV (Qiagen)
Tech development for cervical cancer screening and visualization MobileODT Gynocular Potential advantages: Ensure patient gets the right kind of treatment Improved record-keeping Improved supervision and oversight Issues: Cost Data ownership Overdiagnosis Evidence of effectiveness?
Tech development for cervical pre-cancer - Treatment New treatment of precancerous lesions: Thermal coagulation (WiSAP, Cure Medical) Cryopen Cryopop Cryopop Issues: Evidence of efficacy and safety Availability and cost Cryopen Thermal coagulation
Issues to consider for adoption National registration, guidelines WHO recommendations Cost device, plus consumables Infrastructure needs electricity, water, clean air Time Ease of use for nurses, lab techs, doctors Patient acceptability Procurement and supply chain what consumables are needed?
Did you learn? The issues and lessons learned in secondary prevention strategies and barriers to scaling best practices Are you able to discuss approaches with new technologies, HPV-DNA testing and treatment options, including thermal coagulation
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