Ann Laros, MD University of Iowa Sept 17, 2013 Less is more (Pap smears) More is more (Vaccinate all) Source: NCI, 2005 Source: NCI, 2005 3 Cervical cancer was #1 cancer killer of US women until 40 years ago Pap widely implemented through 1970s Currently in US 12,000 diagnosed annually 4,000 die annually ▪ Similar to US motorcycle fatalities Most cancers are found in women who ▪ NEVER had a Pap (50%) ▪ OR had a Pap more than 5 years prior (10%) More than 100+ HPV virus types 40+ types infect the genitals of men and women 14 HR HPV types (oncogenic) HPV 16/18 most common HPV vaccines protect against these ▪ HPV2 HPV 16/18 ▪ HPV4 HPV 6/11 and 16/18 Nano-valent vaccine in Phase 3 trials Genital HPV is spread by genital to genital contact. HPV can be spread by same sex encounters. Condoms decrease the spread by about 75%, but do not prevent it. No real test for HPV Most infections resolve in 1-2 years 60-70% sexually active college students have HPV 20% risk with each partner 70-80% life time risk HPV causes genital warts 1% young men/women get genital warts each year 10% life time risk HPV causes abnormal Paps 10% of young women will have an abnormal pap each year 40% life time risk Why? Why so much change? Did we really need to change? Are they safe? Are we going to miss cancers? How do we do this and the Affordable Care Act too? Dr. Melik: You mean there was no deep fat? No steak or cream pies or hot fudge? Dr. Aragon: Those were thought to be unhealthy—precisely the opposite of what we now know to be true. —From the 1973 Woody Allen comedy “Sleeper.” Develop evidence based cervical cancer prevention guidelines to best serve women, independent of cost 4,000 articles, 1.4 million women over 8 years Stakeholders ACHA, ACOG, AAFP, ACS Nurse Practitioners in Women’s Health Planned Parenthood, + 21 more Recommendations were presented, discussed prior to vote 66% agreement before acceptance First do no harm NO Paps before age 21 Paps every 3 years age 21-29 Paps every 3-5 years 30-65 Normal Pap, every 3 years Normal Pap and negative HPV, every 5 years No change based on HPV vaccine status No Paps after 65 or hysterectomy, if no CIN2+ Seriously ▪ Cervical cancer less than 21 is 1/1,000,000 Cervical cancer rates are low in young women <21 year olds 21-25 year olds 1.4/1,000,000 1.4/100,000 When the risk of cancer is low, the risks of a testing maybe higher. Age of first pap <20 EU country Austria, Slovakia(18) 20 Germany, Greece(4.6), 21 23 25 30 Slovenia(16) US(8.5) Denmark(12.9), Sweden(8.7) Belgium, Czech Republic, France, Ireland, Italy(8.2), Poland, Romania(29), UK Finland (4.4), 31 http://eu-cancer.iarc.fr Lithuania(25.6), Netherlands, Spain Bulgaria(25.8) This is NOT new The USPSTF recommends screening for cervical cancer in women ages 21 to 65 years with cytology (Pap smear) every 3 years . Grade: A Recommendation We are not alone Pap interval Every year EU Country Austria, Czech Rep, Germany, Greece (4.6), Slovakia (18) Every 2 years Every 3 years Bulgaria (25.8) Belgium, France, Italy (8.2), Lithuania (25.6), Poland, Sweden Every 3-5 years US (8.5), Denmark (12.9), Ireland (12.9), Spain (7.6), Sweden, UK Finland (4.4), Netherlands, Every 5 years http://eu-cancer.iarc.fr Romania (29) The key is getting it done ▪ 50% of cervical cancers in the US occur in women who have never had a Pap ▪ Finland starts at 30, Paps every 5 years—4.4 ▪ Slovakia starts at 18, Paps annually—18 ▪ US starts at 21, every year—8.5 ▪ Has your mother had a Pap smear? Two acceptable options for screening in this population PREFERRED Pap and HPV Co-testing every 5 ACCEPTABLE Pap every 3 No HPV testing Reflex testing Co-testing No HPV testing Under 25 Reflex testing If Pap is ASCUS, then test for HPV ▪ If ASCUS, +HPV—colposcopy ▪ If ASCUS, -HPV—same as normal, follow-up in 3 years Co-testing If Pap is NORMAL, then test for HPV ▪ Some systems get HPV on all co-tested Paps, not usually useful for LSIL and above Pap after 30 Normal Pap Repeat in 3 years OR HPV testing ▪ HPV negative ▪ ▪ ▪ ▪ Repeat in 5 years HPV positive Repeat in 1 year OR HPV 16/18 testing HPV 16/18 negative Repeat in 1 year HPV 16/18 positive Colposcopy No sooner than age 30. Pap based Pap Normal Normal OR HPV Negative Positive Neg 16/18 Pos 16/18 Action Rescreen in 5 years Repeat in 1 year w/ co-testing Repeat in 1 year w/ co-testing Colposcopy Normal LSIL or greater ASCUS ASCUS No Co-testing No HPV is done Negative Positive Repeat in 3 years ASCCP guidelines, no change Rescreen in 5 years ASCCP guidelines, no change NEGATIVE PAP LIQ CYTO HPV HIGH RISK RESULT POSITIVE (A) HPV 16 GENOTYPE POSITIVE (A) HPV 18 GENOTYPE NEGATIVE No screening following adequate negative prior screening Even if they have a new partner!! “Adequate negative prior screening” not defined IF history of CIN2+, routine Pap for 20 years ▪ Every 3 years Paps screen for cervical cancer, NOT vaginal cancer. Vaginal cancer is NOT common (840 deaths/year) Exceptions: Cervix remains (supracervical hysterectomy) ▪ Follow guidelines until age 65 CIN2+ including cervical cancer No changes in frequency. As of 2010, 20.5% women age 19-26 reported > 1 HPV vaccine This low vaccine uptake is a barrier to making population based changes. Iowa was among the worst Look for vaccine related changes no sooner than 10 years. Iowa Lags Behind Rest of US in HPV Vaccination Iowa’s vaccination rate for genital human papillomavirus (HPV) is below the national average, which itself has a low rate of compliance, according to Philip Colletier, president for the Polk County Medical Society. A recent CDC report showed that only 33 percent of children had completed the three-shot sequence since the United States approved it in 2006 for girls and in 2009 for boys. Colletier said that Iowa’s completion rate was only 21 percent and education was the key to increasing this rate. Des Moines Register (08.23.2013) Get the HPV vaccine, soon Men can get the HPV vaccine All men up to age 21 Some men through to age 26 Vaccinate your sons and daughters Protect your daughters Protect your sons Vaccinate MSM Based on “similar treatment for similar risk” In addition to large population research studies, data from Kaiser in California with 1.4 million women over 8 years. Women of different ages have different risks. <21 21-24 25-29 30+ Risk for CIN3+ in 5 yrs Recommendation 5% 2-5% .01-2% .01% Colposcopy F/up 6-12 months Pap in 3 years Pap/HPV in 5 years No paps under 21 If LSIL or ASCUS, ignore those done If +HPV, ignore it No endocervicals cells, no worries Age matters 21-24 No HPV reflex testing 21-24 No colp for LSIL No more 6 month follow-up More HPV testing (over 30 and in follow-up of abnormals) 1. Unsatisfactory Pap—Repeat in 2-4 months 2. No endocervical cells—Normal, repeat in 3 yrs 3. ASCUS Pap—Repeat in one year (not 6 mns) 4. ASCUS, -HPV Pap—Normal, repeat in 3 years 5. AGUS—Colp. No HPV triage recommended Represents inadequate cell collection HPV testing requires adequate cell collection as well. Many HPV tests don’t have a fail safe for inadequate vs not present. Therefore can’t rely on NEGATIVE HPV in this setting. If unsatisfactory x2, immediate colposcopy With liquid based paps, occurs in 10-20%; higher in older women. Review of KPNC, these women a have no higher risk for CIN 3+ Including patients after treatment for CIN 2+ Remember: In 1950, 4 out of 5 doctors recommended Camels Repeat in one year If ASCUS or worse—colposcopy ▪ 2 ASCUS leads to colposcopy, but they may be 1 year apart, instead of 6 months If normal—repeat in 3 Women under 25 (21-24) with ASCUS PREFERRED: No reflex HPV testing; repeat in one year x2. ACCEPTABLE: Reflex HPV testing, OK* *Neither ASCUS HPV+ nor HPV- women go to colposcopy. “Normal” Repeat in 3 years (not 5) If 65, this should not be the last Pap ▪ Repeat in one year 1. No colp for women under 25 with < LSIL 2. Moderate dysplasia can be followed in “young women”. Followed with colp in 6 months for up to 2 years 50% resolve LSIL and HPV testing Recommend reserve only for postmenopausal Stigma of HPV Anxiety of disease, follow-up Cost and time for follow-up Pain and injury from follow-up Increased risks for preterm delivery Recommendations for women sexually active under 21 Folic acid daily Chlamydia testing yearly Flu vaccine annually (HPV vaccine complete) (Effective contraception) (Exercise and healthy diet) No Pap 1 in 8 babies delivers prematurely in the US Too much Pap testing led to too many biopsies and too many treatments and is one of the factors contributing to preterm birth Cervical cancer is not hereditary. Most HPV infections resolve in 1-2 years We are not looking for mildly abnormal cells, but severely abnormal cells On average it is 3-7 years from CIN3+ to cancer Cervical cancer is a disease of younger women, peak age 40. Breast, colon cancers increase Heart disease increases more Regular exercise and a healthy diet Is it safe to Do a physical without a routine UA? Give the pill without a cholesterol? Give the pill without a Pap? Place an IUD in a nullipara? Eat margarine? Do Paps every 3 years? How well are we doing? Quality assurance audits Paps under 21 Colps/referrals under 25 (ASCH, HSIL, AGUS only) HPV vaccinations men <21 Back to back Paps after 2013 Test time 19 y/o presents for yearly and birth control Sexually active since 15 19 sexual partners, HSV Mother with cervical cancer Last Pap 3 years ago A. It has been 3 years, do Pap B. No Pap, test for HPV C. No Pap, test for Chlamydia D. She is at high risk, do Pap E. Chastity belt and Mom talk Answer, C. No Paps before age 21, SERIOUSLY Chlamydia testing is recommended for all sexually active women under 26 yearly Sexually active women are likely to have HPV, don’t test women under 30 for HPV Cervical cancer is not heritable. It is caused by the HPV virus 33 year old G2P2 for annual exam No abnormal Paps Pap today is normal When is her next Pap due? A. Next year B. 3 years C. 5 years Answer, B Paps every 3 years If co-testing with HPV had been ordered and HPV was negative, then 5 years Take home lesson, Unless your provider is George Clooney or McDreamy , ask for HPV co-testing with your Pap 20 year old Pap: ASCUS, +HPV Options A. Refer for colposcopy B. Repeat Pap in 6 mnths C. Repeat Pap in 12 mnths D. Repeat HPV in 12 mnths Answer, C. Repeat the Pap in 12 months. Send the referring provider, up to date and informative follow-up letter. Set up a QI/QA survey in your own department. STRONG recommendation for no Pap until age 21. IF Pap obtained before 21, ignore unless CIN2+ 50 year old P5 Last Pap 201o. No abnormal Paps Hysterectomy for fibroids When is her next Pap due? A. Today, it has been 3 years B. Every 5 years if HPV was negative C. Never more. Thank Gosh for evidence based medicine Answer, C. Never more Primary care providers ARE great Modeled impact of target screening age on incidence of cervical cancer* Target Age (years) 20–64 25–64 30–64 35–64 Reduction in CA Incidence (%) No. of Tests 84 9 84 8 81 7 77 6 Modeled using a 5-yr screening interval ,assuming a 70% sensitivity of the 1st screening test. Data from IARC: Working Group on Evaluation of Cervical Cancer Screening Programs: Screening for squamous cervical cancer. BMJ 293:659, 1986. 40 year old P2 Supracervical hysterectomy Pap with HPV co-testing ▪ Pap= NORMAL ▪ HPV=POSITIVE What do we do now? A. Repeat Pap in one year B. Repeat Pap in 3 years, it is normal C. Refer for colposcopy D. Refund her money, she didn’t need a Pap, she had a hysterectomy Answer, A. Repeat in one year. Normal Pap Repeat in 3 years OR HPV testing ▪ HPV negative ▪ HPV positive Repeat in 1 year OR We are looking for precancerous cells, not HPV If HPV 16/18 positive, then COLPOSCOPY Supracervical hysterectomy, leaves the cervix 25 year old Pap: ASCUS, HPV negative Options: A. Refer for colposcopy B. Repeat Pap in 6 months C. Repeat Pap in one year D. Repeat Pap in 3 years Answer: D, Repeat Pap in 3 years Question: Does the risk of precancerous change in women with ASCUS, HPV- warrant greater surveillance than normal Pap, HPV-?No Negative HPV is great. Studies show no different in risk compared to negative co-test (neg Pap and neg HPV). 21 year old First Pap: LSIL Based on 3/2013 guidelines A. B. C. D. E. Colposcopy HPV testing, colposcopy of HPV+ HPV 16/18 testing, colposcopy if either positive Repeat Pap in 6 months Repeat Pap in one year Answer: D, Repeat Pap in 1 year In a young healthy woman, likelihood of resolution in 1-3 years is high, 90% Likelihood of developing cancer in this time, low, low. 21 year old First Pap: HSIL PLAN: A. Colposcopy B. HPV testing, colposcopy if positive C. HPV 16/18 testing, colposcopy if positive D. Repeat Pap in 1 year Answer, A. Colposcopy High grade, is still high grade Avoid HPV testing under 30 32 year old LEEP for moderate dysplasia age 22 All normal Paps yearly since Pap: Normal Options: A. B. C. D. Colposcopy Repeat Pap in 1 year Repeat Pap in 3 years Repeat Pap and co-testing in 5 years Answer: C, repeat Pap in 3 years After treatment for CIN2+, there is an increased risk for cancer that lasts 20 years. Recommendation has been for regular/annual Pap smears for 20 years. Now, Pap every 3 years for 20 years, even if this puts her greater than 65. Initial clearance, co-test (Pap and HPV) at 12 and 24 months. If all negative, every 3 years for 18 more years. 27 year old Mild dysplasia on colposcopy PLAN: A. Repeat Pap in 6 months x2 B. Repeat Pap in 1 year C. HPV testing D. Cryo Answer, C (preferred); (or A, acceptable) HPV testing in one year If POSITIVE , repeat colposcopy If negative, return to routine screening OR Pap x2 6 months apart. Colposcopy for ASCUS or greater 21 year old Last Pap LSIL, 18 months ago No follow-up w/ recommended colposcopy Options A. Refer for colposcopy B. Pap with HPV testing C. Pap only today D. HPV testing only today Answer, C Colposcopy is no longer recommended for women under 25 unless HSIL/AGUS. ▪ After 1 year, 70% of mild dysplasia is resolved ▪ After 3 years, 90% of mild dysplasia is resolved Follow LSIL for 24 months in women <25. Generally avoid HPV testing in women <30, ▪ except with ASCUS or in follow-up of known MILD DYSPLASIA until age 30. 53 year old Pap normal, no endocervical cells Plan: A. Repeat in 2-4 months B. Repeat in 1 year C. Repeat in 3 years D. Repeat in 5 years Answer: C, repeat in 3 years If she had had HPV “co-testing”, 5 years. 2-4 months is for UNSATISFACTORY, meaning not enough cells, not no endocervical cells 34 year old P5 with LSIL Pap Colp adequate, Cx bx: Mild dysplasia EndoPap: LSIL Options A. LEEP or Cone biopsy B. Cryo or laser C. HPV testing at one year D. Pap x 2, 6 months apart Answer: C (preferred); D (acceptable) LSIL or CIN 1 in endocervix is NOT indication for LEEP/Cone and should be treated like mild dysplasia. Treatment is NOT recommended for Mild dysplasia 23 year old with history of an abnormal Pap She thinks she had colposcopy. She recognizes mild or moderate dysplasia, NOT severe. She does not remember cryo (freezing and thawing), laser (burning with smoke evacuator/vacuum), LEEP She recalls a normal Pap last year, 2011. Options (Records are not available) A. Pap only today B. Pap with HPV testing today C. HPV only testing D. Repeat pap in 3 years Answer: No true answer Based on her history recall and age, most likely abnormal Pap is LSIL or ASCUS, +HPV. IF colp was performed and no treatment was recommended, either unremarkable or mild dysplasia. IF mild dysplasia, 2 Paps or one HPV test is adequate follow-up. MY answer Ask your gynecologist or referring entity A. Pap only today 24 year old Humira for Rheumatoid Arthritis Pap last year normal Does she need a Pap this year? A. Yes B. No Answer: No data. No recommendations Probably yes, her medication weaken her immune system and her ability to clear the virus.