10/31/2018. P r i m a r y H P V S c r e e n i n g : W h a t t o e x p e c t i n t h e n e a r f u t u r e. Disclosure Statement.

Transcription

1 P r i m a r y H P V S c r e e n i n g : W h a t t o e x p e c t i n t h e n e a r f u t u r e C H R I S T I N A H O N G M D 19 TH I N T E R R E G I O N A L S Y M P O S I U M N O V E M B E R 2, Disclosure Statement Today s faculty: Christina Hong MD and the planners for this activity, as well as the CME staff, do not have any relevant financial relationships with commercial interests or affiliations to disclose. % Cervical Cancer Facts: 13,240 Cases in ,170 deaths year survival

2 Incidence per 100,000 women Invasive Cervical Cancer Incidence SEER Tumor Registry, From a screening perspective, it is critical to consider the substantial amount of invasive cancers that occur in women aged Cancer of the Cervix Uteri (Invasive). SEER incidence and US death rates, age-adjusted and age-specific rates, by race. Table Accessed Mar 01, The Global Burden of Cancer 274,000 deaths yearly worldwide 492,000 cases yearly worldwide The Road to Primary HPV Screening 1950s 1970s 1990s Pap Smear ACOG HPV First HPV Test Co-testing ASCCP Widespread use of Pap cytology begins in the US ACOG recommends annual Pap testing for women >18y IARC classifies HPV16 and HPV18 as carcinogenic FDA approves first HPV test ASCCP/ACS publish interim guidelines for HPV adjunct testing Clinical update for HPV genotyping after ASCUS Pap results 6 2

3 The Road to Primary HPV Screening Co-testing Screening Interval Primary Screening Primary Screening USPSTF ACS, ASCCP, ASCP, and ACOG: cotesting is preferred method for women >30y at 5 year interval USPSTF endorses HPV testing to increase cancer screening interval FDA approves first HPV DNA test for primary screening SGO/ASCCP publish interim guidance for the use of primary HPV screening for women >25y Interim guidance for primary screening 7 HPV TYPES IN CERVICAL CANCER HPV16/18 are associated with over 70% of cervical cancers HPV16 (54.4%) HPV18 (16.5%) > 70% HPV58 (5.1%) > 92% HPV33 (4.7%) HPV45 (4.4%) HPV31 (3.6%) HPV52 (3.4%) Other (7.9%) 8 Crow (2012). Nature Outlook Durst et al. (1983). PNAS Boshart et al. (1984). EMBO Journal Detection of HPV DNA in tumors initially established the virus linkage to cancer HPV Infections in the United States 79 million Americans are currently infected with HPV 14 million new infections occur each year year old individuals account for 49% of all new HPV infections Most HPV infections clear on their own; however, persistence of certain HPV types can lead to clinically significant diseases (eg, certain HPV-related cancers and diseases) For HPV-associated cervical disease, it cannot be reliably predicted which patients with infection or abnormal cytology will progress to clinically significant disease versus spontaneously regress. 3

4 Estimated Annual Cases of HPV-related Cancers and Diseases Caused by 9 HPV Types for Males and Females in the US in 2016 Estimated Annual Cases Vulvar and vaginal cancers 4,700 Anal cancers 6,800 Cervical cancers 11,800 High-grade cervical precancers 216,000 Genital warts 320,000 Low-grade cervical lesions 468,700 HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58. References: 1.American Cancer Society (ACS). Cancer Facts & Figures Atlanta, GA: American Cancer Society; de SanjoseS et al. EurJ Cancer. 2013; 49(16): AlemanyL et al. EurJ Cancer. 2014;50(16): AlemanyL et al. IntJ Cancer. 2015;136(1): de SanjoseS et al. Lancet Oncol. 2010;11(11): Centers for Disease Control and Prevention (CDC). Chapter 5: Human Papillomavirus. In: Roush SW, McIntyre L, Baldy LM, eds. Manual for the Surveillan ce of Vaccine Preventable Diseases. 5th ed. Atlanta, GA: Centers for Disease Control and Prevention; 2012: Guan P et al. IntJ Cancer. 2012;131(10): JouraEA et al. Cancer EpidemiolBiomarkers Prev. 2014;23(10): Garland SM et al. J Infect Dis. 2009;199(6): Colposcopy HPV Carcinogenesis 4

5 Radical Hysterectomy Limitations of Cytology Cytology has low sensitivity for detecting CIN2 or worse 1 Multiple attempts have been made to improve it s sensitivity Work load limits: CLIA 1988 Liquid-based cytology: late 1990 s Computer-assisted screening: late 1990 s Cytology is less effective in detecting AIS and adenocarcinoma 2 Identifies individuals with cancer precursors but not women at risk of developing these 1. Castle et al. (2011). Lancet Oncol 2. Kinney et al. (2011). Gynecol Oncol Screening Option #1 Cytology screening Rescreen 3 yrs Pap- HPV- Rescreen 3 yrs Pap ASC-US HPV Test >ASC-US Colposcopy HPV+ Colposcopy Women 21-29: Recommended screening method* Women 30-65: Acceptable screening option* Saslow et al. (2012). AJCP 2. ACOG practice bulletin 157 (2016) 3. Massad et al. (2013). JLGTD *Per ACS, ASCCP, ASCP screening guidelines and ACOG Practice Bulletin 1,2 Management strategy may be different for women years of age 3 5

6 Screening Option #2 HPV & Pap co-testing: multiple screening and management paths NILM/HPV- ASC-US/HPV- Rescreen 5 yrs Rescreen 1 yr Pap HPV Test NILM/HPV+ OR HPV16/18 HPV16/18- HPV16/18+ Rescreen 1 yr Colposcopy ASC-US/HPV+ >ASC-US Colposcopy Women 30-65: Preferred screening option* Saslow et al. (2012). AJCP 2. ACOG practice bulletin 157 (2016) 3. Massad et al. (2013). JLGTD *Per ACS, ASCCP, ASCP screening guidelines and ACOG Practice Bulletin 1,2 ASC- US/HPV-: co-test at 3 years 3 LSIL/HPV-: repeat co-testing at 1 yr is preferred 3 P r i m a r y H P V S c r e e n i n g The Cobas HPV Test Simultaneous results for pooled hrhpv genotypes and individual results on the highestrisk genotypes HPV16 and HPV18 An internal cellular control (β-globin) monitors the presence of human cells and is intended to reduce false-negative results 18 cobas HPV Test Package Insert, Doc. Rev

7 The Athena Study ,209 women 25 y/o Validation of cobas HPV Test First screening trial for registration that simultaneous included genotyping Liquid based cytology The Athena Study Validation of the cobas HPV Test and Hybrid Capture 2 (hc2) in the ASC-US population for detection of CIN2 Significantly improves upon other commercially available HPV tests by individually identifying HPV 16 and 18 while simultaneously detecting 12 other hrhpv genotypes as a pooled result The absolute risk of CIN2 was 31.5% among women who were HPV 16 positive 2 Pooled hrhpv negative women were at low risk of CIN2 2 Women who were HPV 16 positive were more than twice as likely to have CIN2 than those women who were pooled hrhpv positive 2 Clinical implications for the cobas HPV Test from ATHENA in women with normal cytology Women who are HPV 16 positive with normal cytology had a 13.6% absolute risk of CIN2; therefore, nearly 1 in 7 women who tested positive for HPV 16 had high-grade cervical disease that was missed by cytology. 3 Women who are HPV 16 positive are at the highest risk of cancer. 3 The cobas HPV Test supports a safely extended screening interval for women with normal cytology who are HPV negative, similar to other hrhpv DNA tests. The cobas HPV Test allows a reduction in the screening burden on physicians and their patients. 7

8 Cumulative Incidence Rate CIN3 (%) GENOTYPING OFFERS HPV RISK STRATIFICATION HPV16/18 genotyping identifies women at highest risk of cervical pre-cancer 12,976 women 30 years and older; NILM cytology Risk based on HPV status at enrollment Genotyping facilitates the identification of women at highest risk for cervical cancer CIN3+ 22 Khan et al. (2005). JNCI HPV Genotyping Evidence-based risk stratification HPV16+ 42,209 women 25 years and older Cytology & hrhpv testing at enrollment Genotyping facilitates the identification of women at highest risk for cervical cancer HPV other hrhpv+ HPV16+ HPV18+ hrhpv DNA+ hrhpv DNA- HPV- Years of Follow-up Women 25 years and older verification bias adjusted 23 Wright et al. (2015). Gynecologic Oncology Performance of Screening Strategies over a 3-year period using dataset of Athena Cytology with HPV testing only for ASC-US Hybrid strategy Cytology ages y/o Cotesting 30 y/o HPV primary strategy HPV-negative women rescreened at 3 years 8

9 Prevalence of CIN3+ per 10,000 women CIR CIN3 (%) Proportion of CIN3+ Safety of HPV Testing Disease Detection + Reliability of a Negative Result Critical demands for Cervical Cancer Screening High-grade Disease (CIN3+) High-grade Disease (CIN3+) % % 60% Pap NEG % 20% ASC-US % Age (y) Age (y) More CIN3+ in women 25-29y than all other age groups Cytology misses more than 50% of CIN3+ cases in women 25-29y 26 Wright et al. (2015). Gynecologic Oncology ATHENA, Roche Data on File Disease Detection + Reliability of a Negative Result Critical Demands for Cervical Cancer Screening Pap Negative 0.32 HPV Negative Baseline Year 1 Year 2 Year 3 Women 25-29y with negative cytology had a 5x higher risk of developing CIN3+ over three years than women with a negative HPV test 27 ATHENA, Roche Data on File 9

10 Sensitivity for CIN2 (%) CIN3+ cases detected Limited sensitivity of cytology HPV primary screening increases detection of CIN3+ ATHENA Study 40,901 women 25 years Total CIN3+ cases detected over 3 years HPV Primary Screening Cytology* 100% increase 48% increase Age Wright et al. (2015). Gynecologic Oncology Saslow et al. (2012). AJCP ACOG practice bulletin 157 (2016) *Per ACS, ASCCP, ASCP screening guidelines and ACOG Practice Bulletin 1,2 HPV Primary Screening improves Detection of Disease (Sensitivity) Precancers Stage 3 & higher Found by Triage of borderline Pap Found by Cotesting Found by HPV Prim. Screening ATHENA clinical trail. HPV Data on file ; Women 25+ HPV TESTING OVERCOMES LIMITED SENSITIVITY HPV DNA testing increases sensitivity for detecting high-grade lesions Average increase 35.7% Cytology HPV DNA Test 0 Bigras (N=13,842) Cardenas (N=1,850) Coste (N=3,080) Kulasingam (N=774) Mayrand (N=9,977) Petry (N=7,908) Studies performed in developed countries in women 30 years and older. 30 Whitlock et al. (2011). Ann Intern Med. 10

11 Safety and Effectiveness HPV negative result provides greater reassurance of low CIN3+ risk than cytology Population/Study N Negative test at entry 3-year CIN3+ risk 5-year CIN3+ risk 3-year cancer risk 5-year cancer risk Kaiser Permanente Northern California 1,011,092 HPV Cytology ATHENA 42,209 HPV 0.34 Cytology 0.78 Ronco: 4 European trials Dillner: 7 European studies 176,464 24,295 HPV Cytology HPV Cytology Huh et al. (2015). Gynecologic Oncology Huh et al. (2015). Obstet Gynecol Huh et al. (2015). J Lower Gen Tract Dis FDA NEWS RELEASE APRIL 24, FDA approves first human papillomavirus test for primary cervical cancer screening Cobas HPV Test The U.S. Food and Drug Administration today approved the first FDAapproved HPV DNA test for women 25 and older that can be used alone to help a health care professional assess the need for a woman to undergo additional diagnostic testing for cervical cancer. The test also can provide information about the patient s risk for developing cervical cancer in the future. COBAS HPV TESTING 33 Primary HPV Screening 2015 SGO and ASCCP guidance recommendations Professional societies convened to provide interim guidance: Primary HPV screening is an alternative to current cervical cancer screening methods due to equivalent or superior effectiveness A negative hrhpv test provides greater reassurance of low CIN3+ risk than a negative cytology result Women 25 and older Begin 3 years after last negative cytology if woman was screened by cytology prior to age 25 Rescreen no sooner than 3 year interval Only FDA-approved assay with specific primary HPV screening indication Performance characteristics vary between HPV tests so assumptions around test comparability should not be made Huh et al. (2015). Gynecologic Oncology 11

12 ACOG Practice Bulletin Number 157, January 2016 In women 25+, primary HPV screening can be considered as an alternative to current cytology-based screening methods ASCCP and SGO interim guidance should be followed: Not for women younger than 25 Rescreening following a negative HPV test should not occur sooner than every 3 years Positive results should be triaged with a combination of HPV16 and HPV18 genotyping and cytology; patients with negative triage tests should be re-screened in 1 year Only an FDA-approved test for primary screening should be used 34 Huh et al. (2015). Gynecologic Oncology Final Recommendation Statement: Screening for Cervical Cancer August 21, 2018 Women aged 21 to 65 years benefit from screening. Pap test for women aged 21 to 29 years 3 strategies to screen women aged 30 to 65 years: Pap test HPV test Both in combination (cotesting). Recommendation Summary Released August 21, 2018 The USPSTF recommends screening for cervical cancer every 3 years with cervical cytology alone in women aged 21 to 29 years. For women aged 30 to 65 years, the USPSTF recommends any of the following: Cervical cytology screening alone every 3 years Co-testing (cytology and HPV) every 5 years Primary high-risk human papillomavirus (hrhpv) testing alone every 5 years 12

13 Joint Statement of ACOG, SGO and ASCCP to USPTF Screening Method #3 Primary HPV screening; Women 25+ HPV- Routine Screen HPV Test HPV16/18 12 other hrhpv+ Pap NILM Repeat LBC/HPV ASC-US Colposcopy HPV16/18+ Colposcopy 38 Wright et al. (2015). Gynecologic Oncology Huh et al. (2015). Gynecologic Oncology *Primary Screening is only FDA-approved currently for ThinPrep PreservCyt specimens S o u t h e r n C a l i f o r n i a P e r m a n e n t e M e d i c a l G r o u p W H A T T O E X P E C T W I T H T H E F U T U R E O F C E R V I C A L C A N C E R S C R E E N I N G 13

14 Cervical Cancer Screening Overview Objective: Provide the best quality, evidence-based cervical cancer screening & follow-up care for our members Recent advances in cervical cancer screening allow for better and more reliable detection of pre-cancer & cancer Implementation of these evidence-based innovations will result in improved follow-up care workflows & potentially better outcomes for our members In doing so, we also remain in line with FDA approvals, United States Preventative Services Task Force (USPSTF) recommendations, HEDIS guidelines, & other national recommendations and guidelines SCPMG Consulting and Implementation Cervical Cancer Screening Update Friday, 09/07/2018 SCPMG s cytology (pap) collection system in SCPMG No FDA approved HPV test until 2016 FDA Concern Around Safety of SurePath In 2013, BD, in collaboration with the FDA, sent warning letters to laboratories using SurePath with HC2, warning of the potential for False Negatives Under existing guidelines, a false-negative test result could lead to the absence of patient follow-up and, ultimately, to preventable cancer progression. BD Inc. Technical Bulletin May accessed July

15 SurePath Issues Formaldehyde Crosslinking of nucleic acids Pre-treatment procedure to reverse SurePath-induced cross-linkage developed by Roche Molecular Systems for their Cobas HPV test Decided to partner with SCPMG & the FDA to see if Cobas would work in Surepath HPV Testing in Specimen Transport Medium (Dual Collection) Kaiser Permanente Results positive or negative No genotyping 2 nd sample collected separate from pap smear SCPMG and Cervical Cancer Screening Kaiser Permanente Co-collection Surepath for pap PreserCyt for HPV testing (Hybrid Capture 2 test) Why co-collection or dual collection Until 2016, no FDA approved HPV test in Surepath 2016 FDA approval for Cobas HPV test in Surepath Remove need for dual collection Cost savings Potential for primary HPV screening and genotyping 15

16 856 women enrolled Primary endpoint completed in May 2015 FDA submission December 2015 Am J Clin Pathol 2017;00:1-8 Genotype prevalence in two Cobas HPV trials First US clinical trial including HPV vaccinated population cobas HPV Test Results (%) Age Groups (Years) HPV 16+ HPV Other HR HPV+ HPV- SurePath ATHENA SurePath ATHENA SurePath ATHENA SurePath ATHENA Trial Trial* Trial Trial* Trial Trial* Trial Trial* Overall * ATHENA ASC-US population COB-HPV-269: 31.8% vaccination rate in ASC-US population ATHENA: 4.3% vaccination rate in ASC-US population 1 ; 2.6% in all eligible women Stoler et al. (2011). Am J Clin Pathol 2. Wright et al. (2011). AJOG Performance of cobas HPV Test: CIN3+ Non-vaccinated vs vaccinated in SurePath clinical trial cobas HPV Test HC2 using STM Point Estimate 95% CI Point Estimate 95% CI Sensitivity (%) 92.3% (12/13) (66.7, 98.6) 93.3% (14/15) (70.2, 98.8) Non-vaccinated Vaccinated 57.7% 57.3% Specificity (%) (53.6, 61.7) (53.4, 61.1) (325/563) (362/632) 99.7% 99.7% NPV (%) (98.6, 99.9) (98.7, 99.9) (325/326) (363/363) Prevalence 2.3% (13/576) 2.3% (15/647) 100% 100% Sensitivity (%) (70.1, 100) (70.1, 100) (9/9) (9/9) 49.8% 48.4% Specificity (%) (43.8, 55.8) (42.5, 54.3) (130/261) (133/275) 100% 100% NPV (%) (97.7, 100) (97.8, 100) (130/130) (133/133) Prevalence 3.3% (9/270) 3.2% (9/284) 49 cobas HPV Test Package Insert, Doc. Rev

17 SCPMG Cervical Cancer Screening Taskforce , Significant strategic quality in initiative in women s health Group Individual Title Leads Clinical Representatives Complete Care Laboratory Consultants Other Lawrence Lurvey, MD David Quam, MD Lyn Yasumura, MD Christina Hong, MD Devansu Tewari, MD Robert Pretorius, MD Tracy Imley, MD Timothy Ho, MD Anita Joshua Jane Tongson-Ignacio, MD Jonathan Gullett, MD Ruan Ramjit, MD Gary Gochman, MD Timothy McSkane Dennis Sevilla, PhD Kenneth Van-Horn, PhD Louie Farnacio Vahe Khanlian Katie Tower Melanie Pitts Sarah Weinberger Ridhima Iyer Colposcopy teams IT/KPHC Regional Assistant Medical Director of Quality, Risk, Regulatory Services, and Maternal Child Health Regional Assistant Medical Director of Laboratory Care Delivery System & Regional Reference Laboratory System Regional Chief of OB/GYN OB/GYN Representative OB/GYN GYN ONC Representative OB/GYN GYN ONC Representative Internal Medicine Representative Regional Assistant Medical Director of Quality & Complete Care Regional Consultant, Proactive Panel Management & Cancer Screenings Physician Director of Cytopathology Physician Director of Microbiology Physician Director of Molecular Genetic Pathology Regional Chief of Anatomic Pathology Executive Leader, Laboratory Care Delivery System & Regional Reference Laboratory System Director Anatomical Pathology Technical Director of Microbiology Director of Operations, Regional Reference Laboratories Director of Operations, Regional Reference Laboratories Senior Manager Managerial Consultant Regional Quality Manager Intern Interregional Collaboration with TPMG Education Initial Phase Implementation SurePath Vial Conversion & HPV Genotyping Implementation Because of advances in cervical cancer screening that allow for better & more reliable detection of pre-cancer & cancer, the following will be implemented in 2018: Initial Phase Implementation Conversion to new version SurePath vials HPV Genotyping Explanation Both Cytology (Pap Smear) and HPV specimens will be collected using new versions of the SurePath vial (continue to collect as 2 separate specimens in 2 separate vials, according to age guidelines) Using the original HPV specimen, the lab will test for specific high risk HPV genotypes, associated with a high risk of developing cervical cancer Implementation Timeline: Conversion to new version SurePath vials: November 2018 HPV Genotyping: Tuesday December 4, 2018 Reasoning Allows use of new molecular platform for HPV genotyping Over 70% of invasive cervical cancers are linked to HPV genotypes 16 and/or 18 This will not impact our CSG performance, as no changes will be made to the screening method 17

18 Conversion to New Version SurePath Vials Current Process Pap Smear Specimen Collection Older Version SurePath Vial New Process Pap Smear Specimen Collection New Version SurePath Vial Vial #1 HPV Specimen Collection Digene Collection Tube HPV Specimen Collection New Version SurePath Vial Vial #2 53 Conversion to New Version SurePath Vials Smaller opening Insert the head of the broom-type device into the LARGER of the two vial openings Rotate the handle of the collection device while gently pulling up to detach the device head from the handle, depositing the device head into the LARGER of the two vial openings DO NOT use the smaller opening DO NOT drop the Rover Cervex-Brush or Cytobrush/Spatula into the smaller opening Rover Cervex- Brush Plastic Spatula & Cytobrush Use a NEW collection device (brush or spatula) with each vial. Each vial should be sent to the lab with the head of a collection device (brush or spatula) in the larger opening. Otherwise, there will not be enough specimen in the vials to run the tests. Collection Process with the New Version SurePath Vial BD SurePath Test sample collection with Rovers Cervex brush 1. Collect: Collect the cytology sample using a broom-like device with detachable heads. 2. Drop: Use the interior rim of the new BD SurePath Collection Vial to pull off the head of the broomlike device into the LARGE opening in the collection vial. 3. Send: Place the cap on the vial and tighten. Send the BD SurePath vial to the lab for processing. Collection process with the Rover Cervex Brush is very similar to your current process Note: If you use the Plastic Spatula and/or Cytobrush for collection, utilize your current process for collection Snap the device handle & drop the detachable head into the larger opening 18

19 PAPrescreen Follow-up based on type 5 yrs of Pap result HPV(-) PAP SMEAR & HPV SCREENING Appropriate Age PAP(+) COLPOSCOPY follow-up Every 5 years HPV(+) Pap (+) or (-)? PAP SMEAR & HPV PAP(-) / PAP SMEAR & HPV PAP(-) RESCREEN IN 1 YEAR HPV(-) RESCREEN IN 3 YEARS PAP(-) / HPV(-) rescreen 5 years PAPrescreen 5 yrs PAP SMEAR & HPV SCREENING Age Every 5 years HPV(+) PAP(-) / HPV(-) rescreen 5 years HPV(-) HPV 12 OTHER(+) HPV 12 OTHER(+) or HPV 16/18(+)? HPV 16/18(+) Follow-up based on type of Pap result PAP(+) Pap (+) or (-)? PAP(-) COLPOSCOPY PAP SMEAR & HPV RESCREEN IN 1 YEAR COLPOSCOPY PAP(-) / HPV(-) Appropriate follow-up PAP SMEAR & HPV RESCREEN IN 3 YEARS Appropriate follow-up HPV+ Follow-up Algorithms Notes: No change to the algorithms for other age groups No change to the collection tube or algorithm for chlamydia screening Age Age Current Algorithm PAPrescreen 3 yrs PAP SMEAR Age Every 3 years Follow-up based on type PAP(+) of Pap result HPV(-) HPV SCREENING Specimen processed (Specimen collected at pap smear appt) Appropriate HPV(+) COLPOSCOPY follow-up Initial Phase No change Algorithm Single Specimen Collection & Genotyping Changes listed in green Final Phase Implementation Single Specimen Collection, Primary HPV Screening, & Dual Staining Cytology The implementation of single specimen collection & genotyping in 2018 will poise KP SCAL to be able to implement Primary HPV Screening: Final Phase Implementation Primary HPV Screening Single Specimen collection Dual Staining Cytology Explanation HPV testing with genotyping will be utilized as the initial means of routine cervical cancer screening (depending on the test results, cytology and/or colposcopy may be subsequently utilized for screening & follow-up purposes) Cervical Cytology (Pap Smear) & HPV specimens will be collected in one SurePath vial for laboratory processing Using the original specimen, the lab will test for cervical epithelial cells demonstrating the expression of both p16 & Ki-67 biomarkers (when indicated by patient results & screening algorithm) Reasoning Provides results that are more sensitive & inform more appropriate follow-up care than cytology-based screening Provides an easier method for collecting and analyzing Cervical Cytology & HPV specimens, allowing for more consistent results Evidence suggests potential to better triage colposcopy need for patients who are negative for HPV 16/18, but positive for the 12 other high risk HPV genotypes (not yet FDA approved our implementation will follow FDA approval) Implementation Timeline: TBD, depending on HEDIS recommendations Much more will be shared on Primary HPV screening as we get closer to the timeframe for implementation Implementation Timeline: SurePath Vial Conversion & Genotyping September 2018 Presentations to Leadership Groups October 2018 Educational WebEx trainings for Physicians, Providers, & staff about genotyping o Wed 10/03 11am-12pm or 12:30pm-1:30pm or 2pm-3pm o Thu 10/18 11am-12pm or 12:30pm-1:30pm Materials Management orders new version SurePath Vials Present to leadership from OB/GYN, Family Medicine, Internal Medicine, Urgent Care, Pathology, Complete Care, Ambulatory Care Practice Leaders, Cervical Dysplasia Coordination, & Materials Management (Sept Oct 2018) November 2018 November: New version SurePath vials stocked in clinic Note: Do not use the new version SurePath vial for HPV specimen collection prior to Tuesday, 12/04/2018 (OK to use new version SurePath vial for cytology specimen collection prior to Tuesday, 12/04/2018) Lab representatives site visits to provide education about new version SurePath vials (Sept Nov 2018) December 2018 Tuesday, 12/04/2018: o Use new version SurePath vials for cytology & HPV specimen collection o Genotyping results become available Note: Lab & materials Management will assist with removal of Digene collection tubes TBD 2019: Communication & Implementation of Primary HPV Screening (a more detailed timeline will be provided when a date for implementation is determined) 19

20 Percentage Score Percentage Score Z-Score Z-Score Site Visits by Laboratory Team Laboratory representatives will visit all applicable sites from late September through mid November to provide information Medical Center Site Visit Dates Number of MOBs/Clinics (2018) Panorama City September 24 & Woodland Hills September 26 & 27 9 LAMC October 1 & 2 8 West LA October 3 & 4 10 Fontana October 8 & 9 6 Ontario October 10 & 11 7 San Diego Zion October 15 & San Diego Clairmont October 17 & Riverside October 22 & 23 6 Moreno Valley October 24 & 25 7 Anaheim October 29 & Irvine October 31 & November 1 7 Downey November 5 & 6 8 South Bay November 7 & 8 9 Baldwin Park November 9 & 12 5 Antelope Valley November 12 & 13 9 Kern County November 12 & 14 4 Laboratory Training Contacts: Arnold Gacusan, Elvira Martin, Marianne Muyrong, and Ryan Quilatan Departments to Visit: Clinical Lab, Materials Management, OB/GYN, IM, FM and UC (including MOBs) HPV Vaccination Overview Efforts focus on improving the rate of HPV vaccinations in adolescent male & female patients CSG Goal: Improve the HPV vaccination rate of patients age 9-13 to 55% HealthyPeople 2020 Goal: Improve the HPV vaccination rate of patients age to 80% HPV vaccination helps protect against multiple forms of cancer in males and females CSG Metric: Current HPV Vaccination Rates Average Vaccination Rate = 53.7% The percentage of patients, age 9-13, who received at least two HPV vaccine doses (with at least 146 days between the first and second dose) or three HPV vaccine doses (with different dates of service) 100.0% 80.0% 60.0% 40.0% 20.0% 0.0% 100.0% 90.0% 80.0% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% HPV Vaccination SCAL Regional Average 51.5% 52.0% 52.4% 52.9% 53.1% 53.3% 53.7% Dec Jan Feb Mar Apr May Jun % 47.1% % 51.2% 51.8% 52.0% 53.7% 56.3% 56.8% SBC SD WH RI DO KC SCAL REG HPV Vaccination Medical Center Results (June 2018) % % % 62.1% 62.3% Percentage Score Target (CSG Goal 55%) Z-Score Percentage Score Target (CSG Goal 55%) Z-Score PC LA BP WLA OC SBY AV

21 Barriers to HPV Vaccination: Vaccine Hesitancy In , an online survey was conducted to better understand HPV vaccine refusal and delay This survey included 1,504 parents of adolescents with mean age of 14 years Of the parents surveyed, that refused 28% HPV reported vaccination, that they had the most refused frequently HPV Vaccination reported reasons for HPV vaccine refusal (>20%) were: Believing their child was not sexually active (57%) Concern about lasting health problems (50%) Need more information (44%) Believing their child did not need HPV vaccine (34%) Most helpful sources of information on HPV vaccination (>20%) reported by parents: Talking to a doctor (75%) Reading an information sheet (53%) Watching a video (21%) Reference: Gilkey MB et al. Hum Vaccin Immunother Jun 2; 12(6): Physician Communication About Adolescent Vaccination: How Is HPV Vaccine Different? In an online survey of US physicians to assess physicians perceptions and communication practices related to recommending adolescent vaccines for 11- and 12-year-old patients (n=776): Only 13% of physicians perceived HPV vaccine as being highly important to parents, which was far less than perceived parental support for Tdap (74%) and meningococcal vaccines (62%). Physicians reported that discussing HPV vaccine took almost twice as long as discussing Tdap. Among physicians with a preferred order for discussing adolescent vaccines, most (70%) discussed HPV vaccine last. Reference: Gilkey MB et al. Prevent Med. 2015;77: Importance of a Clear Recommendation for 19- to 26-Year Olds Health care professional recommendation is a strong predictor of HPV vaccination. In a survey of 530 women years of age, health care professional discussion or recommendation of the HPV vaccine increased the odds of infiltrating the vaccination schedule by 93-fold Reference: Rosenthal, SL et al. Vaccine. 2011;29(5): Survey was conducted in

22 Questions? 22