Human Papillomavirus (HPV) and Cervical Cancer Prevention

Size: px

Start display at page:

Download "Human Papillomavirus (HPV) and Cervical Cancer Prevention"

Andrea Hutchinson
6 years ago
Views:

1 Human Papillomavirus (HPV) and Cervical Cancer Prevention MOA Autumn Convention November 3, 2017 David J Boes, DO, FACOOG (Dist.) Associate Professor, MSU-COM 1

2 Disclosures None relative to this presentation 2

3 Learning objectives Discuss PRIMARY & SECONDARY PREVENTION Apply 2017 CDC HPV Vaccination recommendations Advise patients on safety and efficacy of HPV vaccination as well as appropriate age groups Dispel myths by evidence-based counseling Review/update appropriate screening options and recommendations for cervical cancer screening Be aware of most current data on cytology & hrhpv testing Follow evidence-based recommendations to evaluate women with abnormal cervical cancer screening results 3

Death rate has declined by 74% in the past 50 years (era of screening) 4%

4 Cervical Cancer 80% squamous type 20% adenocarcinoma type 99% attributable to HPV U.S. Death rate has declined by 74% in the past 50 years (era of screening) 4% decline every year continues Average age of diagnosis is 50 Precursor lesion precedes invasive carcinoma by 10 years, but can be quicker in some 4

5 HISTORY OF WOMEN DIAGNOSED WITH CERVICAL CANCER 50% HAVE NOT HAD A PAP SMEAR IN THE LAST 5 YEARS 15% HAD A RECENT NORMAL PAP THAT HAD TRULY ABNORMAL CELLS PRESENT (false negative) 10% HAD AN ABNORMAL PAP BUT NO FOLLOW-UP 25% HAD A RECENT NORMAL PAP SMEAR 5

6 Natural History of Cervical Neoplasia Human Papilloma Virus (HPV) HPV is necessary component Most HPV infected women will not develop significant cervical cytology abnormalities Risk Factors Early onset intercourse Multiple partners Cigarette Smoking (2-4 x increased risk) HIV Immunosuppressed Past history of high grade lesions Not risk factor: family history 6

7 HPV Infections Infection with specific high risk strains of HPV is central to the pathogenesis of cervical cancer High risk [hrhpv]..(15 oncogenic types) 16,18,31,33,35,39,45,51,52,56,58,59,68,69,82 Cervical cancer: 66% (16,18) 15%: (31,33,45,52,58) HPV 6 & 11 (non-oncogenic) Genital Warts (90% from 6 & 11) LSIL (low grade squamous intra-epith. Lesions) 7

8 HPV & HPV VACCINE HPV is associated with Anogenital Cancer Cervical Vaginal Vulvar Penile Anal Oropharyngeal cancer Genital warts HPV Vaccination: significantly reduces risk of Anogenital cancer Genital warts MAY reduce risk of oropharyngeal and transmission to fetus 8

9 HPV VACCINATION Complicance in U.S. with vaccination guidelines: 42% OF Females in recommended age group 28 % of Males in recommended age group U.S. rates unacceptably low (compared to other developed countries) 3 FDA approved vaccines: Bivalent (being discontinued) Quadrivalent (discontinued in U.S) Nine-valent (replacing quadrivalent) 9

10 PREVENTION SAFE SEX Condoms may reduce HPV transmission by up to 70% (primary prevention) HPV VACCINATION Initial vaccine: Protection against HPV 16,18 which accounts for 70% of Invasive cervical ca (primary prevention) New vaccine: Gardasil 9* has the potential to prevent approximately 90 percent of cervical, vulvar, vaginal and anal cancers. *Gardasil 9 covers: (hrhpv) OncogenicTypes 16, 18, 31, 33, 45, 52, and 58; and HPV Types 6 and 11 ( cause of genital warts) SCREENING: [HPV or CYTOLOGY) This is considered secondary prevention since we are not actually impacting the cause of cervical cancer 10

11 HPV vaccine Benefits Risks Recommendations Safety 11

HPV VACCINE Recommendations Girls & Boys [ages 9-26] Age 11-12 (target initiation) Up to

12 HPV VACCINE Recommendations Girls & Boys [ages 9-26] Age (target initiation) Up to Age 26 (approved) Vaccine is most effective if initiated before onset of sexual activity 12

Timing of Vaccination Age <15: target age 11-12 (may begin at age 9-14) 2 doses: (1) Baseline, (2) 6-12 months Note: If interval between 2 doses is <5 months, a 3 rd dose is

13 Timing of Vaccination Age <15: target age (may begin at age 9-14) 2 doses: (1) Baseline, (2) 6-12 months Note: If interval between 2 doses is <5 months, a 3 rd dose is recommended Interval > 12 months not recommended, in order to assure both doses given before onset sexual activity Age >15: catch-up 3 doses: Baseline, 1-2 months, 6 months (after baseline) 13

Strategies to improve compliance Health care providers: Education of parents Ob-gyn or Primary provider should assess & vaccinate adolescent girls-boys/ young

14 Strategies to improve compliance Health care providers: Education of parents Ob-gyn or Primary provider should assess & vaccinate adolescent girls-boys/ young women-men during catch-up period (ages 13-26) Dispel Urban Myths: HPV vaccination is NOT associated with an earlier onset of sexual activity or increased STI s 14

safety CDC data: If we had an increase in HPV vaccination rates to 80%, an additional

15 Patient Education Studies show Physicians recommendations play a crucial role in the acceptance of HPV vaccination by patients and parents of patients Emphasize benefits and safety CDC data: If we had an increase in HPV vaccination rates to 80%, an additional 53,000 cases of cervical cancer could be prevented during lifetime of those younger than age

16 Adolescent sexual activity Incidence of sexual activity 1/3 of 9 th graders 2/3 of 12 th graders Vaccine effectiveness: Greater if given prior to sexual activity 16

17 SAFETY of HPV VACCINE 60,000,000 doses since 2006 No Data TO SUGGEST ADVERSE EFFECTS Institute of Medicine (independent) J. of Internal Medicine: large cohort study no concerns, 2017 LOCAL (transient) REACTION post injection Do not administer if history of life-threatening allergic reaction to any component of the HPV vaccine 17

18 SPECIAL POPULATIONS NO risks known to be associated with pregnancy Safe in breastfeeding Immunosuppression: (HIV or organ transplantation): NO CONTRAINDCATION 3 DOSE REGIMEN is recommended 18

19 FAQ s Testing for hrhpv before Vaccine: Not Recommended Does not change recommendations for vaccine? Vaccinate if prior hx of HPV (abn pap or genital condy): Yes Vaccination is recommended regardless of sexual activity or prior exposure to HPV Pregnancy testing before vaccine: Not recommended No harm to fetus if exposed 19

20 FAQ s (continued) What if HPV vaccine series interrupted due to pregnancy? Resume series PP with the next dose Vaccine series does not need to be restarted Can Breastfeeding woman receive vaccine Recommended. NO harm Adverse effects? Mild local discomfort after vaccination Minimize with NSAID, Acetominophen 20

21 FAQ s (continued) Should booster vaccine be administered? No current indications Is the protection as good with 9 valent vaccine Yes: antibody titers not reduced Should patient be RE-VACCINATED if prior 3-dose vaccine with quadrivalent? Not currently recommended If patient initiated bi or quad-valent, may switch to nine-valent 21

guidelines (same as unvaccinated women) WHAT TO DO IF

22 Special Circumstances If a patient has received the HPV vaccination, they should still follow recommended guidelines (same as unvaccinated women) WHAT TO DO IF RECEIVED QUAD VACCINE, AND NOW NEW GARDASIL 9 VACCINE IS AVAILABLE.?? 22

23 Screening SECONDARY PREVENTION DETECT PREMALIGNANT LESIONS Colposcopy for abnormal screen Ablative & Excisional procedures 23

24 Why Screen for Cervical CA 3rd most common cancer in women 13,000 cases per year, 4000 deaths (U.S.) 5 year survival rates near 100% for treated stage 1a, whereas survival rate for stage IV disease is 5-15% HPV infection prevalence is 20-40% in women years old 24

25 Screening for Cervical CA changing guidelines (since 2006) When to start screening Age related frequency of screening Primary screening: Cytology or HPV (or both)??? When is hrhpv testing indicated When to stop screening Management guidelines 25

26 SCREENING RECOMMENDATIONS [as of 2017] Major organizations/guidelines American Cancer Society USPTSF (United States Preventive Task Services Force) ACOG (American Congress of OB-GYN) ASCCP (American Society for Colposcopy and Cervical Pathology) ASCP (American Society for Clinical Pathology) Guidelines 2012 (updated 2015) 26

27 2016 GUIDELINES Cervical Cancer Screening 27

28 Who should be screened? Women who have been sexually active and have a cervix (level A *evidence), (after age 21) Rationale: Screening with cervical cytology reduces the incidence of and mortality from cervical cancer. Use of extended tip spatula & cytobrush to sample endocervix is supported by medical evidence *A. The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms. 28

29 AGE TO START AGE 21 Irregardless of age of onset of sexual activity No one under age 21 needs pap/cervical cancer screening 29

30 Rationale (for later screening) So why the changes? HPV Infection: Natural History Very common in younger women Prevalence of HPV infection decreases as women ages Infects transformation zone, squamous metaplasia active in adolescence >80% of infections cleared by immune system in 2 years in young women Most HPV + patients have normal cytology Risk of neoplasia increases with persistence of infection Most dysplasia in adolescents regresses spontaneously 30

31 Rationale (for later screening) So why the changes? Invasive Cervical age 21: RARE SEER*: 1-2 cases/1,000,000 females age Based on low incidence of < age 21 Based on potential for adverse effects associated with follow-up of young women with abnormal cytology screening results *Surveillance Epidemiology & End results,

32 Optimal Frequency of CYTOLOGY SCREENING [2017--current] AGE 21-29: EVERY 3 YEARS AGE 30 & OLDER: every 3 years (cytology alone), Every 5 years if HPV & cytology co-testing MORE FREQUENT SCREENING, if : HIV + IMMUNOSUPPRESSION DES PRIOR TX FOR CIN 2-3 OR CA Based on test sensitivity, patient harm, & cost 32

33 Cervical Cancer Screening- When to Stop Women may consider stopping screening at age 65, IF No history of neoplasia, adenocarcinoma or cancer Either 3 consecutive negative pap tests or 2 consecutive negative co-tests within the last 10 years (most recent within last 5 years) NO HX DES EXPOSURE NO IMMUNOSUPPRESSION She may discontinue pap tests at this time based on criteria - this does NOT guarantee she won t develop cervical cancer 33

34 Women aged 65 and older*: Continue to offer screening for cervical cancer to women with a good life expectancy who have risk factors for cervical cancer a history of an abnormal Pap test current smoker or history of smoking, unknown prior Pap test history, previous HPV-related disease new partners beyond age 65 years* ASCCP says NO PAP after age 65, irregardless of new partner (generally until about age 80, but the upper limit of offering screening may vary with the risk factor). *from UP TO DATE: Literature review current through: Apr This topic last updated: Apr 04,

35 STOP SCREENING AT AGE 65 SCREENING SHOULD NOT RESUME FOR ANY REASON, EVEN IF A WOMAN REPORTS HAVING A NEW SEXUAL PARTNER ASCCP,

36 Rationale for stopping at 65 years CIN 2+ is rare after age 65 Most abnormal screens, even HPV +, are false + and do not reflect precancer HPV risk remains 5-10% Colposcopy/biopsy/treatment more difficult Harms are magnified Incident HPV infection unlikely to lead to cancer within remaining lifetime ASCCP,

37 Special Circumstances Screening in a patient who has had a total hysterectomy (uterus and cervix) No screening is necessary if no cervix AND no history of CIN 2 or 3, adenocarcinoma in situ, or cancer in the past 20 years 37

38 Abnormal Pap Results Age HGSIL, ASC-H, AGUS- Colposcopy Age ASCUS HPV positive- colposcopy HPV negative- repeat co-testing in 3 years LGSIL, HGSIL, ASC-H, AGUS- all Colposcopy 38

39 When is HPV TESTING indicated? Determination of the need for colposcopy in women with an ASC-US cytology result ( reflex testing ), AGE As an adjunct to cytology screening in woman age ( cotesting ) Optional: Primary cervical cancer screening in woman 25 years and older (see next slides) 39

40 40

41 2017 USPSTF AGE CYTOLOGY EVERY 3 YEARS OR Hr HPV every 5 years No co-testing (HPV & Cytology) 41

42 USPSTF 2012 GUIDELINES 42

43 USPSTF 2017 DRAFT GUIDELINES 43

44 RESPONSE FROM ACOG, ASCCP, & SGO letter dated October 9, 2017 Urge retention of 5-year co-testing as screening option, age Recommend shorter interval for primary hrhpv screening There is a lack of U.S. Validation studies for 5- year screening interval for hrhpv Concern that insurance may deny co-testing, still the preferred method by ACOG,ASCCP, and SGO 44

45 Managing Abnormal Pap Smears ASCCP ALGORITHIMS & GUIDELINES: (free ) 45

46 USEFUL PHONE APP, has all Algorithms 46

47 CASES 47

48 Case # 1 An 18 year old women comes in to have a check up and asks about when she should be having her first annual female exam. She is sexually active x 3 years and has had 3 partners. You counsel her on the current recommendations for initiation of screening for cervical cancer. What are key points to consider? WHAT IF SHE HAS HAD HPV VACCINE? WHAT IF SHE IS PREGNANT? 48

49 Suggest screening should start at age 21 (ACOG) [irregardless of age of onset of coitus, and # of partners] Reflex HPV test should be done after 25 if (+) ASCUS (DO NOT DO HPV TESTING BEFORE AGE 25) Screening should occur every 3 years until age 30 Screening may be changed to every 5 years at 30 Should have HPV co-testing if choosing this option 49

50 Case # 1 (Continued) Three years later (age 21), she has her first pap smear as directed and it is normal. At age 23, she has a pap smear with ASCUS What would you suggest in regards to follow up? 50

51 As she is 21-24, she would get a repeat pap in 1 year ASCUS/LGSIL - repeat pap in 1 year If she was between ASCUS - reflex HPV testing Positive - colposcopy Negative - repeat pap in 3 years From age 21-29: HGSIL, ASC-H or AGUS - colposcopy THIS IS VERY CONFUSING, LUCKILY THERE S AN APP FOR THAT! 51

52 Case: 45 year old female, average risk Patient at age 45, decides to have testing every 5 years with HPV testing At age 50, she has a pap smear with ASCUS, HPV NEGATIVE What would you suggest now? 52

53 ASCCP APP ($9.99) 53

54 She should have repeat co-testing in 3 years If she had been HPV positive colposcopy Everything else Proceed to colposcopy: LGSIL/HGSIL ASC-H AGUS 54

55 Case # 1 Your patient is now 65 and wants to discuss stopping pap smears She has not had an abnormal pap smear since her one at 45 How would you counsel her? 55

56 CASE #2 36 y/o, G0P0 (wishes to preserve fertility) Nov. 2013: Pap CYTOLOGY: LSIL HIGH RISK HPV PANEL: (co-testing, >age 30) PAST PAPS: NEGATIVE TOBACCO: NO PMH: No co-morbidities CONTRACEPTION: LOW DOSE COC SEE NEXT SLIDE 56

57 NOVEMBER, 2013; pap: LSIL + High Risk Panel can prompt genotyping WHAT IS NEXT STEP? 57

58 NEXT STEP COLPOSCOPY TWO REASONS: LSIL : OVER AGE 30, ALWAYS PROCEED TO COLPOSCOPY + HPV 18 COLPOSCOPY RESULTS: 58

59 MANAGEMENT ACI: (ADENOCARCINOMA IN SITU) If DONE WITH CHILDBEARING HYSTERECTOMY If PRESERVE CHILDBEARING CERVICAL EXCISIONAL PROCEDURE LEEP: WITH DEEP ENDO CX SPECIMEN REVERSE COWBOY HAT AIS TENDS TO INVOLVE ENDOCX, AND SKIPS/MULTIFOCAL ECC, (OVER AGE 35: EMB) 59

60 FOLLOW UP COLPOSCOPY, ECC: APRIL 2014 LEEP OR CONE: MAY 2014 PLAN: FOLLOW UP TESTING: 6 MONTHS 60

61 NOVEMBER 2014 PLAN: FOLLOW UP TESTING IN 1 YEAR 61

62 NOVEMBER 2015 (1 year later) HPV RESULTS ON NEXT SLIDE 62

63 HPV: NOV

64 MANAGEMENT PLAN HOW WOULD YOU COUNSEL PATIENT? STILL WISHES TO PRESERVE FERTILITY FURTHER EVALUATION NECESSARY AT THIS TIME? DISCUSS CLEARING THE VIRUS (NEG HPV TESTING) IS REASSURING AND LOWERS RISK OF RECURRENCE OR PERSISTENCE OF AIS 64

65 ADENOCARCINOMA CYTOLOGY ALONE MUCH LESS EFFECTIVE FOR DETECTION (THAN FOR SQUAMOUS CELL CA) CO TESTING : BETTER DETECTION AGUS: ALWAYS DO COLPOSCOPY IN THIS PATIENT, EVEN IF NEGATIVE, SHOULD CONTINUE SCREENING FOR AT LEAST 20 YEARS 65

66 SUMMARY of current guidelines See next slides 66

67 2016 GUIDELINES 67

68 MGT OF SCREENING RESULTS 68

69 > AGE 30, CYTOLOGY NEG, HI RISK HPV POSITIVE 69

70 Cervical cancer screening should begin at age 21 years. With the exception of women who are infected with HIV, women younger than 21 years should not be screened regardless of the age of sexual initiation or the presence of other behaviorrelated risk factors. Women aged years should be tested with cervical cytology alone, and screening should be performed every 3 years. Cotesting should not be performed in women younger than 30 years. Annual screening should not be performed 70

71 For women aged years, cotesting with cytology and HPV testing every 5 years is preferred; screening with cytology alone every 3 years is acceptable. Annual screening should not be performed. Liquid-based and conventional methods of cervical cytology collection are acceptable for screening. Liquid-based and conventional methods of cervical cytology collection are acceptable for screening. 71

72 Screening by any modality should be discontinued after age 65 years in women with evidence of adequate negative prior screening test results and no history of CIN 2 or higher. Adequate negative prior screening test results are defined as three consecutive negative cytology results or two consecutive negative cotest results within the previous 10 years, with the most recent test performed within the past 5 years. In women who have had a hysterectomy with removal of the cervix (total hysterectomy) and have never had CIN 2 or higher, routine cytology screening and HPV testing should be discontinued and not restarted for any reason. 72

73 Women with any of the following risk factors may require more frequent cervical cancer screening than recommended in the routine screening guidelines, which were intended for average-risk women: Women who are infected with HIV Women who are immunocompromised (such as those who have received solid organ transplants) Women who were exposed to diethylstilbestrol in utero Women previously treated for CIN 2, CIN 3, or cancer 73

74 Thank you 74

Making Sense of Cervical Cancer Screening

Making Sense of Cervical Cancer Screening New Guidelines published November 2012 Tammie Koehler DO, FACOG The incidence of cervical cancer in the US has decreased more than 50% in the past 30 years because