Lisa Flowers M.D. FACOG Professor, Department of Gynecology and Obstetrics Director of Colposcopy and Anoscopy Services Associate Chief of Gyn Services Emory University School of Medicine Atlanta, GA Cervical Cancer Screening Is It Ever Safe to Stop in Postmenopausal Women? What’s the Risk of Atypical Glandular Cells? NAMS 2015 Annual Meeting External Industry Relationships * Company Name Role Equity, stock, or options in biomedical industry companies or publishers None Board of Directors or officer None Royalties from Emory or from external entity None Industry funds to Emory for my research None Other None Lisa Flowers MD Personal/Professional Financial Relationships with Industry 2 Learning Objectives Explore the data on cervical cancer screening in postmenopausal women and whether it decreases the incidence of cervical cancer. Investigate the risks and benefits of screening in the postmenopausal women. Evaluate the optimal age for a women’s last cervical cancer screening test. Analyze the importance of Atypical Glandular Cells and risk of cervical cancer in the postmenopausal women 3 Current Cervical Cancer Screening Recommendations Cervical Cytology screening every three years ages 21-65 Co-testing with cytology and HPV testing every five years ages 30 to 65 Primary HPV testing every 3 years: 25-65 years of age End date of age 65 if 3 negative Pap tests or 2 negative co-tests in the preceding 10 years and no history of CIN 2+ disease in the last 20 yrs
Transcript
Lisa Flowers M.D. FACOG Professor, Department of Gynecology and Obstetrics Director of Colposcopy and Anoscopy Services Associate Chief of Gyn Services Emory University School of Medicine Atlanta, GA
Cervical Cancer Screening Is It Ever Safe to Stop in Postmenopausal
Women?
What’s the Risk of Atypical Glandular Cells?
NAMS 2015 Annual Meeting
External Industry Relationships * Company Name Role
Equity, stock, or options in biomedical industry companies or publishers
None
Board of Directors or officer None
Royalties from Emory or from external entity
None
Industry funds to Emory for my research
None
Other None
Lisa Flowers MD Personal/Professional Financial Relationships with Industry
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Learning Objectives
Explore the data on cervical cancer screening in postmenopausal women and whether it decreases the incidence of cervical cancer. Investigate the risks and benefits of screening in the postmenopausal women. Evaluate the optimal age for a women’s last cervical cancer screening test. Analyze the importance of Atypical Glandular Cells and risk of cervical cancer in the postmenopausal women
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Current Cervical Cancer Screening Recommendations
Cervical Cytology screening every three years ages 21-65 Co-testing with cytology and HPV testing every five
years ages 30 to 65 Primary HPV testing every 3 years: 25-65 years of
age End date of age 65 if 3 negative Pap tests or 2
negative co-tests in the preceding 10 years and no history of CIN 2+ disease in the last 20 yrs
High-risk human papillomavirus (HPV) among women aged 57–85, 2005-2006.
The overall population-based weighted estimate of high-risk HPV prevalence by hc2 was 6.0% (95% confidence interval [CI] = 4.5 to 7.9). A nationally-representative probability sample of community-dwelling adults aged 57–85 was generated from US households screenedin 2004 for the Health and Retirement Study (HRS) . Source: Prevalence of High-Risk Human Papillomavirus Among Older Women ; Stacy Tessler Lindau, MD, MAPP,1 Melinda L. Drum, PhD,2 Elyzabeth Gaumer, MA,3 Hanna Surawska, BA,4 and Jeanne A. Jordon, PhD5; Obstet Gynecol. 2008 Nov; 112(5): 979–989. doi: 10.1097/AOG.0b013e31818b0df2
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57–64 65-74 75-85
Hr-HPV Prevalence (%) among women 57-85
(%)
Age group and number N=33 N=376 N=302
Natural History of High-Risk HPV Infection and Potential Progression to Cervical Cancer
Why the Peak in Cervical Cancer Rates in Women 60-69 year of age?
Under or never screened populations comprise up to 40% of cervical cancer cases. However 60% of the cases are in a screened population. – Compliance with screening decreases with
age – Protection from screening is time-limited – Efficacy of screening in the older women
may be lower
Why the Peak in Cervical Cancer Rates in Women 60-69 year of age?
Sawaya et al. Review of 455 women from 1988-1995 diagnosed with ICC in the KPNC plan under the same insurance for ≥ 30 of the 36 months prior to diagnosis. – No Pap test 6-36 months prior to dx
53% – Normal Pap tests
28% – 1 abnormal Pap test with adequate follow-up
9% – 1 abnormal Pap test with inadequate f/u.
4%
Screening and Future Risk of ICC What Needs to be Considered?
Are well-screened women with a history of negative tests and no history of high grade dysplasia at a sufficiently low risk of cervical cancer that screening can stop at age 65?
If so, how low is their risk and does it change as they age?
Are women who regularly engage in screening at 50-64 years of age at a reduced risk of ICC at age 65-83?
Screening History Prior to a Diagnosis of ICC in Women 65 or Older?
Risk of Cervical Cancer at age 65-83 y by screening history at age 50-64 y
Screening History At Age 50-64 Cases
N=1341 Controls N=2646
OR No Screening as ref.
n Percent n Percent OR 95% CI Adequate negative 288 21.5 1,395 52.7 0.16 0.13-0.19 Suboptimal but negative 300 22.4 724 27.4 0.34 0.28-0.42 Abnormal 221 16.5 98 3.7 1.83 1.37-2.43 No Screening 532 39.7 429 16.2 1 ref
Women who were not screened at age 50-64 were 6 times more likely to develop CC between the ages of 65-83 y compared to screened women. – 20 yr. risk: 8 cancers/10,000 women (screened) vs 49 cancers/10,000
(unscreened) with OR=0.16, 95% CI 0.13-0.19. The magnitude of protection decreases over time since last screen.
Castanon et al. examined screening history of women in the UK from age 50-64 yrs of age and risk of CC at age 65-83.
Screening History Prior to a Diagnosis of ICC in Women 65 or Older?
Dinkelspiel H, Fetterman B, Poitras N, et al. Screening history preceding a diagnosis of cervical cancer in women age 65 and older. Gynecol Oncol 2012;126:203–6.
• KPNC population of 65 yrs and older diagnosed with CC between
2003-2008 • Exit screening: 3 negative consecutive Pap tests or a single co-test • 56 women were diagnosed with CC during a period of 1,323,100
women-years of membership in women age 65 and older • 75% (42/56) did not meet the stopping criteria • 25% (14/56) had 3 consecutive negative Pap tests between 55-65
yrs of age • 3 of these women had one or more negative co-tests • 3/46,401 women with 1 or more negative co-tests at age 65 and
older were diagnosed with CC during 132,639 women-years of follow-up
Is There Data Demonstrating that Screening Older Women Decreases the
Incidence of ICC ?
Study Screening Interval % Incidence Reduction
Kamineni et al USA
Screening ages 55-79 77
Sasieni et al UK
Screening at age 62-64 80
Andrae et al Sweden
Screening age 60 and older 64
Lonnberg et al Finland
Screening age 60 and older 51
Is There Data Demonstrating that Screening Older Women Significantly
Impacts Mortality from ICC ?
Lonnberg S, Nieminen P, Luostarinen T, Attila A. Mortality audit of the Finnish cervical cancer screening program. Int J Cancer 2013;132(9):2134–40. 506 CC deaths and 3,306 controls age-matched between 2000-2009 54% of deaths were in cancers diagnosed more than 5 years after last screening CC risk reduction was seen in the 55-69 age group (OR 0.29; CI -0.16-0.54)
Vicus D, SutradharR, LuY, Elit L,KupetsR, Paszat L. The association between cervical cancer screening and mortality from cervical cancer: a population based case–control study. Gynecol Oncol 2014;133:167–77. 1052 women with CC age matched with 10,494 between the ages of 20-69 between 1998-2008 Women 65-69 risk of dying from cervical cancer was reduced (OR 0.53 CI 0.35-0.79) (p< 0.05) if screening occurred within the prior 3 yrs.
How Long Will a Negative Screening Test Protect a Women from Cervical Cancer?
Study Age Group (year)
Time (yrs) Since Last Negative
Test
OR (95% CI)
Kamineni et al USA
55-79 3 to <5 0.15 (0.04-0.58)
Sasieni et al UK
55-69 5.5 to 6.6 0.33 (0.14-0.79)
Vicus et al Canada
65-69 3-5 0.37 (0.15-0.92)
Castanon et al UK
65-83 ≤5 0.25 (0.21-0.30)
In general a negative cytology test provides 5 years of protection in women over 60 yrs of age from cervical cancer.
The Balance of Harms, Benefits and Costs of Screening the Older Women
Anxiety from false positive tests Difficulty tolerating the colposcopy Distress about have HPV and an abnormal Pap test Perception of increased risk of cervical cancer in the future. Screening even to age 90 years prevents only – 1.6 cancer cases per 1000 women. – 0.5 cancer deaths per 1000 women.
The Balance of Harms, Benefits and Costs of Screening the Older Women
Extends life expectancy by only 1 year per 1000 women, while resulting in – 58 extra false-positive results – 127 extra colposcopies – 13 extra diagnoses of CIN2/3 requiring
treatment. Compared to breast and colorectal cancer, risk of cervical cancer is significantly less at and after the recommended age of screening
Previous HR HPV Testing and Pap Testing Results in Women with CC Zhao et al. retrieved 70 cases of CC from multiple institutions with hrHPV testing and Pap test results 5 yrs prior to the cancer diagnosis.
KPNC study also reported 31% (27/87) of patients with CC had a negative baseline hrHPV test result within 5 years preceding the diagnosis of cervical cancer. Zhao et al. Arch Pathol Lab Med Vol 139, February 2015Katki et al. Lancet Oncol 2011; 12(7): 663-672
So What About Atypical Glandular Cells ?
Significance of Atypical Glandular Cells
Schnatz et.al Obstet Gynecol 2006;107:701-8 Meta analysis of 3,890 AGC Paps +/- ASC-US with f/u Follow-up diagnosis
Cancer may be squamous or adeno. Endometrial cancer not related to HPV status and more common in older women.
Most Likely Disease with AGC is Squamous in Origin
Atypical Glandular Cells
KPNC cohort of 965,360 women, 2003-2010 30-64 yrs of age undergoing co-testing Estimated 5-yr risk of cervical cancer and CIN3+ All HPV negative high grade Pap results had cancer risks high enough to warrant colposcopy.
Pap Results
HPV positivity
5 year Risk of CIN 3+
P value 5 year Risk of CC
P value
HPV+ HPV - HPV+ HPV -
AGC 2,074
25% 33% 0.93% P<0.0001 9.0% 0.37% P<0.0001
ASC-H 1,647
71% 25% 3.5% P<0.0001
2.5% 2.1% P=0.8
HSIL 2,019
94% 49% 30% P=0.006 6.6% 6.8% P=0.7
Atypical Glandular Cells
AGC was most likely to lead to histologic diagnosis of adenocarcinoma – AGC: 1.5%; (31/2074) – ASC-H: 0.2% – HSIL: 0.6% AIS risk was similar between all groups – AGC: 1.8% – ASC-H: 1.1% – HSIL: 1.5%
Atypical Glandular Cells
HPV positivity declined with age –30-34: 44%–60-64: 17%AGC though uncommon is linked with substantial risk of cervical adenoCA or AIS when hrHPV is positive.
In women of 50y and older, a hrHPV-negative result was linked with a 18% chance of extra-cervical malignancy.
A neg HPV with AGC is not Necessarily Reassuring
Verdoodt F, Schnatz PF, et al. High-Risk HPV Testing in the Management of Atypical Glandular Cells: A Systematic Review and Meta-Analysis. Int J Cancer. 2015 Jan 12. doi: 10.1002/ijc.29424
Summary
Cervical cancer screening in older women does decrease incidence and mortality. The optimum age of stopping screening is heavily dependent on screening patterns and results prior to screening cessation. Sexual history or activity does not alter the screening guidelines The cessation of screening at age 65 is not based on data from randomized trials However risks from harms versus benefits suggest that cessation at 65 yrs of age is safe. AGC/HPV positive carries the highest cervical cancer risk of any co-test result except for SCC pap result.
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