- Email: [email protected]
Cervical Cancer Screening and Follow-Up Procedures in Women Age <21 Years Following New Screening Guidelines
ARTICLE IN PRESS Journal of Adolescent Health ■■ (2017) ■■–■■
www.jahonline.org Original article
Cervical Cancer Screening and Follow-Up Procedures in Women Age <21 Years Following New Screening Guidelines Alexandra M. Foxx, M.D. a, Yuwei Zhu, M.D., M.S. b, Edward Mitchel, M.S. c, Sayeh Nikpay, Ph.D., M.P.H. c, Dineo Khabele, M.D. d, and Marie R. Griffin, M.D., M.P.H. e,* a
Vanderbilt University School of Medicine, Nashville, Tennessee Department of Biostatistics Department of Health Policy d Department of Obstetrics and Gynecology e Departments of Health Policy and Medicine, Nashville, Tennessee b c
Article history: Received March 13, 2017; Accepted August 30, 2017 Keywords: Cervical cancer; Cervical dysplasia; Screening guidelines
A B S T R A C T
Purpose: The 2009 American College of Obstetricians and Gynecologists guidelines recommended no cervical cancer screening before age 21 years. We examined changes in screening, diagnostic, and treatment procedures for cervical dysplasia after guideline introduction, and cost implications. Methods: We studied Davidson County women aged 18–20 years, enrolled in Tennessee Medicaid, 2006–2014. We identified those with at least one Papanicolaou (Pap) test, human papillomavirus detection test, colposcopy, or excisional dysplasia treatment annually via Current Procedural Terminology coding. We used rate ratios with 95% confidence intervals to compare annual changes in procedure and treatment rates from 2014 to 2006. We counted total outcomes to estimate annual costs based on 2014 average procedural costs. Results: From 2006 to 2014, about 3,800 Davidson County women aged 18–20 years were enrolled in Medicaid annually. From 2006 to 2014, there were declines in Pap tests from 55.6 to 15.2 per 100 women (rate ratio .27, 95% confidence interval .25–.3); human papillomavirus tests from 13.8 to 5.9 per 100 (.42, .36–.5); colposcopy from 9.4 to 1.1 per 100 (.12, .08–.17); and dysplasia treatment from 1.1 to 0 per 100. The estimated cost of screening and procedures fell from $53 to $8 per enrolled woman, not accounting for changes in visits or complications associated with these procedures. Conclusions: The 2009 screening guidelines were associated with major declines in screening, diagnostic, and treatment procedures for cervical dysplasia. Minimum estimated procedure and treatment costs saved were $45 per enrolled woman age 18–20 years. © 2017 Society for Adolescent Health and Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
IMPLICATIONS AND CONTRIBUTION
Cervical cancer screening declined in young women aged 18–20 years since introduction of 2009 screening guidelines. From 2006 to 2014, Pap smears and colposcopies declined 73% and 88%, respectively, in young women enrolled in Tennessee’s Medicaid program. Results estimated a minimum cost savings of $45 per enrollee.
Conflicts of Interest: The authors have no conflicts of interest to disclose. Sources of study: Tennessee Bureau of TennCare of the Department of Finance and Administration provided the data. Disclosures: HPV IMPACT study was approved as public health surveillance and not research by CDC, Vanderbilt, and TN Department of Health IRBs, 45 CFR 164.512. * Address correspondence to: Marie R. Griffin, M.D., M.P.H., 1500 21st Ave S. Suite 2600, Nashville, TN 37215. E-mail address: Marie.griffi[email protected] (M.R. Griffin). 1054-139X/© 2017 Society for Adolescent Health and Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/). https://doi.org/10.1016/j.jadohealth.2017.08.027
ARTICLE IN PRESS 2
A.M. Foxx et al. / Journal of Adolescent Health ■■ (2017) ■■–■■
Invasive cervical cancer is very rare in women less than 21 years of age [1]; however, minor grade cytology abnormalities are common [2]. Cervical cancer typically results from infection with human papillomaviruses (HPVs). In the United States, genital detection of HPV infections increases through age 24 years and then gradually declines [3]. About 90% of these infections clear in the first two years after acquisition, with regression of accompanying dysplasia [4,5]. Cervical cancer screening modalities include Papanicolaou (Pap) tests to detect abnormal cells and HPV DNA testing to identify oncogenic HPVs [6]. When pre-cancerous lesions are detected, further evaluation may be warranted with colposcopy with or without biopsy. More invasive lesion excision procedures include cryotherapy, loop electrosurgical excision procedure (LEEP), laser ablation, and cold knife conization. Cervical cancer screening and subsequent treatments have significant immediate risks, including anxiety, stigmatization, pain, bleeding, and small bowel injury [6–10]. Systematic reviews of observational studies have found associations between some treatment procedures and perinatal mortality, preterm birth, low birth weight, premature rupture of membranes, and caesarean delivery [7,8]. Many women who undergo these procedures have other risk factors that independently put them at higher risk of adverse pregnancy outcomes. However, procedure-associated risks appear to be related to the amount and/or depth of tissue removed [9–11]. In addition, miscarriage has been associated with pregnancy timing within 12 months of LEEP procedures, but not later [12]. Given the potential for harms from screening and low risk of invasive cancer in very young women, in 2009, the American College of Obstetricians and Gynecologists recommended the initiation of cervical cancer screening at 21 years of age. In addition, they recommended reduced frequency of screenings in other age groups [13]. In 2012, the US Preventive Services Task Force released guidelines in agreement with those of the American College of Obstetricians and Gynecologists [14]. The first HPV vaccine was licensed in the United States in 2006 and recommended by the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices in 2007 for routine vaccination of girls age 11–12 years and catchup vaccination of females 13–26 years. We monitor the incidence of cervical dysplasia in Davidson County (Nashville) women aged 18–39 years as a participating site in CDC’s population-based surveillance, HPV-IMPACT [15], designed to evaluate the effectiveness of the HPV vaccination program on reducing cervical dysplasia incidence. Monitoring changes in screening is an important part of this evaluation. Given that screening is no longer recommended for women aged 18–20 years, we aimed to determine how screening has changed in this group of young women. Population-based data on screening were available for our County for women enrolled in Tennessee’s Medicaid Program (TennCare), which we used to estimate changes following the new screening guidelines. Materials and Methods We performed a retrospective study investigating cervical cancer screening in women 18–20 years of age, who were residents of Davidson County (Nashville), Tennessee, and enrolled in the Tennessee Medicaid program (TennCare). We determined the incidence of Pap smears, HPV DNA testing, colposcopy, and invasive cervical procedures from 2006 to 2014 to deter-
Table 1 Current Procedural Terminology (CPT) coding for specific study procedures Procedure
CPT codes
Pap testing
88141–88143, 88147, 88148, 88150, 8815288155, 88164–88167, 88174, 88175, G0123, G0124, G0141, G0143-G0145, G0147, G0148, P3000, P3001, Q0091 87621, 87623–87625 57420–57452, 57454–57456, 57460, 57461
HPV testing Colposcopy Invasive procedures LEEP/LETZ Cold knife Cryotherapy Ablation or cautery
57461, 57522 57520 57511 57513, 57510
mine the impact of the new cervical screening guidelines. Current procedural terminology codes (Table 1) were used to identify and enumerate the frequency of cervical cancer screening and treatment procedures as reflected in TennCare insurance data. The Tennessee Department of Finance and Administration Bureau of TennCare provided the data. This analysis was performed as part of the HPV-IMPACT study [15], a population-based surveillance of HPV-related disease, and thus considered public health surveillance and not human research by the CDC, Vanderbilt, and TN Department of Health institutional review boards. Davidson County, TN, is one of five HPV IMPACT sites that estimates population cervical cancer screening rates and incidence of cervical dysplasia. The denominator for rate calculations was the number of Davidson County women aged 18–20 years and enrolled in TennCare on July 1 of each year. This method gives an estimate of total person-years of women aged 18–20 years in the population. We counted the number of women with at least one Pap, HPV test, colposcopy, or invasive cervical treatment for dysplasia annually. We also counted total procedures, allowing at most one of each type of procedure per day for each woman enrolled. Screening and treatment procedures (numerators) and estimates of denominators were derived for all women, as well as for nonHispanic white, non-Hispanic black, and Hispanic women as classified in TennCare data. Women with another designation or unknown race or ethnicity were classified as “other.” There were no requirements for continuous enrollment in TennCare for women eligible for this study. We used rate ratios (RRs) to estimate the annual change in procedures performed through 2014 using 2006 as the reference year, and calculated 95% confidence intervals (CIs) using the delta method. We estimated total and average annual costs for all procedures in 2006 and 2014 using actual payments received by providers in the TennCare program. We also calculated overall median costs for each procedure. This approach is consistent with others using Medicaid-managed care data to estimate costs [16] [17]. We excluded all procedures with payments less than or equal to zero from the calculation. Costs were rounded up to whole values and expressed in 2014 dollars using the medical component of the 2006–2014 Consumer Price Index [18]. Results There were about 3,800 Davidson County women aged 18– 20 years enrolled in TennCare annually over the study period ranging from 3,565 women in 2007 to 4,150 women in 2011. The racial or ethnic distribution remained relatively stable, with overall
ARTICLE IN PRESS
Number of Women age 18-20 years
A.M. Foxx et al. / Journal of Adolescent Health ■■ (2017) ■■–■■
3
4500 4000 3500 3000 2500 2000 1500 1000 500 0 2006
2007
2008
2009
2010
2011
2012
2013
2014
Year Black, non-Hipanic
White non-Hispanic
Hispanic
Other
Figure 1. Annual enrollment in TennCare by race or ethnicity for Davidson County women aged 18–20 years, 2006–2014.
57% non-Hispanic black, 28.5% non-Hispanic white, 4.8% Hispanic, and 9.8% other or unknown. In 2014 compared with 2006, there were more women classified as Hispanic and Other and fewer as non-Hispanic black and white, as shown in Figure 1. The number of women aged 18–20 years in Davidson County who had a Pap smear fell from 2,057 in 2006 to 546 in 2014. Pap screening rates declined from 55.6 per 100 women in 2006 to 15.2 per 100 women in 2014 (RR .27, 95% CI .25–.3) (Figure 2A). Pap screening per 100 women declined >70% from 2006 to 2014 in black (from 52.3% to 15.2%), white (from 63.7% to 18.7%), and Hispanic (from 58.0% to 9.6%) women. The number of women undergoing other cervical cancer screening and diagnostic procedures also declined: HPV testing from 346 to 40; colposcopy from 512 to 211; and invasive procedures from 41 to 0. The annual rates of all screening and procedures declined: HPV testing from 13.8 to 5.9 per 100 (RR .42, 95% CI .36–.5), colposcopy from 9.4 to 1.1 per 100 (RR .12, 95% CI .08–.17), and dysplasia treatment from 1.1 per 100 women in 2006 to no events in 2014 (Figure 2B). Average annual costs (standard deviation) in 2014 dollars over the study period were $37.47 (27.93) for Pap tests, $68.14 (48.45) for HPV tests, $131.26 (271.80) for colposcopy, and $753.85 (860.00) for invasive procedures (Table 2). Median annual costs tended to be lower than average costs, because the latter may be influenced by high cost outliers. Median costs overall were $34.84 for Pap tests, $61.63 for HPV tests, $104.62 for colpos-
copy, and $302.15 for invasive procedures. Costs for the entire encounters in which these tests were performed were much higher: $346.80 (329.73) for Pap tests, $289.04 (324.53) for HPV tests, $249.18 (399.62) for colposcopy, and $1,705.15 (1,228.52) for invasive procedures. From 2006 to 2014 estimated annual costs for procedures alone in our cohort dropped from $195,646 to $30,285, an 85% decrease. The contribution of each procedure category to these costs is shown in Figure 3. Accounting for the changes in number of women enrolled per year, the cost fell from an estimated $53 to $8 per woman enrolled or an estimated $45 saved per enrolled woman. Discussion We found declines in all cervical cancer screening and treatment procedures in women aged 18–20 years between 2006 and 2014. Previous studies [19–21] have documented the decrease in Pap tests in young women since the introduction of the 2009 guidelines; however, these studies did not evaluate treatment procedures nor assess cost implications. Young women in our cohort experienced a 73% decline in annual cervical cancer screening with Pap tests from 2006 to 2014. Declines of >70% were observed for black, white, and Hispanic women. Pap test rates appeared stable from 2006 to 2009, and declined steadily thereafter, strongly suggesting that this change was in response to the 2009 guidelines. The guidelines also
Table 2 Estimated average cost and standard deviation (SD) in 2014 US dollars for cervical cancer screening and treatment procedures 2006–2014, Davidson County women aged 18–20 years enrolled in TennCare Pap test Year 2006 2007 2008 2009 2010 2011 2012 2013 2014 Average
Average 34.30 46.37 36.36 37.35 41.07 34.01 38.87 29.44 27.60 37.47
HPV test SD 34.74 27.99 22.65 26.12 32.11 23.27 26.61 20.90 14.99 27.92
Average 83.36 78.00 66.85 64.86 75.69 63.43 75.38 36.64 42.58 68.14
Colposcopy SD 58.74 42.91 35.81 38.36 60.96 43.97 56.06 30.88 28.32 48.45
Average 69.74 153.71 165.03 159.78 181.47 110.00 106.20 125.93 91.45 131.26
Invasive procedure SD 144.86 173.02 462.47 306.24 360.67 63.36 52.81 290.07 32.28 271.80
Average 722.15 653.5 908.92 701.71 1,109.81 504.32 120.57 2,108.70 0 753.85
SD 659.89 538.09 1,149.94 874.53 1,301.74 751.54 NA 2,691.33 NA 860.00
ARTICLE IN PRESS A.M. Foxx et al. / Journal of Adolescent Health ■■ (2017) ■■–■■
a
Annual Pap Tests per 100 Women
4
60 50 40 30 20 10 0 2006
2007
2008
2009
2010
2011
2012
2013
2014
Year
Annual Procedures per 100 Women
18 16 14 12 10 8 6 4 2 0 2006
2007
2008
2009
2010
2011
2012
2013
2014
Year
b
HPV test
Colposcopy
Invasive Procedure
Figure 2. (A) The number of women who received at least one Pap test per 100 Davidson County women aged 18–20 years enrolled in TennCare, by year 2006– 2014. (B) The number of women who received at least one HPV test, colposcopy, and invasive cervical procedure per 100 Davidson County women aged 18–20 years enrolled in TennCare, by year 2006–2014.
$250,000
$200,000
$150,000
$100,000
$50,000
$0 2006
2007 Pap test
2008 HPV test
2009
2010
Colposcopy
2011
2012
2013
2014
Invasive Procedure
Figure 3. Total costs for Pap tests, HPV test, colposcopy, and invasive procedures, Davidson County women aged 18–20 years enrolled in TennCare, by year 2006–2014.
ARTICLE IN PRESS A.M. Foxx et al. / Journal of Adolescent Health ■■ (2017) ■■–■■
recommended no HPV testing for women under 21 years of age. In our cohort, HPV testing was much less common than Pap tests (13.8 vs. 55.6 per 100, respectively) in 2006. However, even this already low incidence of HPV testing declined 57% over the study period. In this population of young women enrolled in TennCare, screening trends were similar for non-Hispanic white, nonHispanic black, and Hispanic women. It is unknown whether continued screening is confined to specific provider or patient populations. Given the continued decline in screening through 2014, practitioners who continue to screen will likely soon be rare. The decline in colposcopies and invasive cervical procedures appeared to begin before 2009. We expected that a decline in screening would result in parallel declines in colposcopies and invasive cervical procedures. Indeed, colposcopy decreased 88% from 9.4 to 1.1 per 100 women from 2006 to 2014, and no invasive cervical procedures were performed in this population in 2014. Although the 2009 guidelines may have resulted in an accelerated decline in colposcopies and invasive surgical procedures, the declines appeared to begin as early as 2006. In 2006, a consensus process composed of 146 experts representing 29 organizations and professional societies developed the American Society for Colposcopy and Cervical Pathology guidelines for the management of women with abnormal cervical cytology [22]. Fauci et al. found that the 2006 guidelines were associated with a decline in referrals of women with cytologic abnormalities categorized as atypical squamous cells of unknown significance to colposcopy [23]. Wieland et al. implemented algorithm-based protocols for triage to colposcopy to assure adherence to these guidelines, and prospectively tracked outcomes. During this intervention from 2006 to 2008, Pap tests changed little, but the number of colposcopy visits and biopsies declined. Notably, guideline-recommended care resulted in fewer cervical intraepithelial neoplasia 1 diagnoses but little change in cervical intraepithelial neoplasia 2 and 3 diagnoses [24]. Finally, Kinney et al. reported an 87% decline in LEEPs in women aged 15–20 years from 2007 to 2011, more modest declines in women 21–29 years, and no change in women 30– 39 years in New Mexico [25]. Changes in guidelines both for screening and for referral to colposcopy as well as HPV vaccine introduction may all have played a role in the large decline in colposcopies and invasive procedures in this age group. HPV vaccines were introduced in 2006 and approved by the US Food and Drug Administration for women 9–26 years old. By preventing acquisition of oncogenic HPVs 16 and 18, vaccination should decrease the incidence of cervical dysplasia, and the need for invasive procedures [26]. The uptake of HPV vaccine should not affect screening, but could affect colposcopy and invasive procedure rates. Vaccine is ideally given before onset of sexual activity, because it is ineffective for those already infected. Nationally, between 2003– 2006 and 2009–2012, representing time periods pre and post HPV vaccine introduction, the prevalence of HPV genotypes represented in the quadrivalent vaccine declined 63% in women 14–19 years, 34% in those 20–24 years, and not at all in women 25–34 years. The declines in HPV prevalence in young women were observed only in those with a history of vaccination, and were confined to HPV vaccine types, providing strong evidence of HPV vaccine impact among women younger than 25 years [27]. Thus, vaccination could have had a role in some of the trends observed in our population. However, vaccine uptake in Tennessee has been low, limiting the potential impact
5
on these trends. Vaccination of Tennessean girls, age 13–17 years with at least one dose of HPV vaccine was 47.8% in 2014, compared with the national uptake of 60.0% for all US girls age 13–17 years [28]. We estimated potential financial implications given the costs of the procedures we enumerated. We estimated, for women aged 18–20 years living in Davidson County enrolled in TennCare, an annual savings of $165,361 in procedural costs in 2014 compared with costs that would have accrued if rates of these procedures were the same as in 2006. Perhaps more compelling, when we account for the change in enrollment over this time period, we still observed the cost fell from an estimated $53 per woman to $8 per woman enrolled or an estimated $45 saved per enrolled woman. This estimate does not account for costs associated with the visit itself, the additional procedures performed at the visit, transportation costs, or other indirect costs. TennCare is a managed care program, thus savings from limiting procedures would accrue to individual managed care organizations rather than the State of Tennessee Medicaid Program. Our estimates of savings are conservative. It is likely that many but not all physician encounters would occur even if Pap and HPV tests were not performed. However, it is likely that there would be some decrease in these visits. However, costs of encounters for colposcopy and invasive procedures were two to three times that of the procedures themselves, and it is likely that many of these costs would also be saved. Potential savings would be higher in settings with higher rates of screening at baseline. Our study has several limitations. We relied on diagnostic and procedure coding to enumerate study screening and treatment outcomes. It is possible that diagnoses or procedures were missed or misclassified. Additionally, generalizability is limited, as all participants were enrolled in TennCare in a single county. This may restrict the relevance of this study to low-income persons in a small geographic area. Of note, private insurance was a strong predictor of cervical cancer screening in prior studies [20], suggesting the impact of the 2009 guidelines in a private insurance cohort could be more dramatic. Additionally, we had no information on knowledge of guidelines by providers. Finally, Medicaid has historically reimbursed providers below cost. Therefore, payments to providers may represent less than the full cost of providing care [29]. However, the difference between costs and payments has been narrowing over time [30]. In conclusion, the decline in cervical cancer screening and associated diagnostic and treatment procedures observed in this study is consistent with a strong impact of both the 2006 (management of cervical dysplasia) and the 2009 (screening) guideline recommendations. HPV vaccination may also have had a role in the decline in diagnostic and treatment procedures. Decreasing the frequency of unnecessary and harmful cervical cancer screening represents an area for cost savings and harm reduction. Although recommendations to delay screening in this age group will benefit most women, this delay may also result in progression of dysplasia in some women. There is evidence that the decline in screening for cervical cancer has resulted in declines in appropriate screening for other sexually transmitted diseases such as chlamydia [31]. These screening activities should be uncoupled. Ultimately, assuring uptake of HPV vaccine is the preferred way to prevent cervical cancer. It will be important to continue to monitor trends in both precancer and cancer in women aged 21 years and older during the HPV vaccine era.
ARTICLE IN PRESS 6
A.M. Foxx et al. / Journal of Adolescent Health ■■ (2017) ■■–■■
Acknowledgments This project was funded through Emerging Infections Cooperative Agreement 5U01C10003. We are indebted to the Tennesee Bureau of TennCare of the Department of Finance and Administration, which provided the data.
[16]
[17]
[18]
References [1] Howlader NNA, Krapcho M, Garshell J, et al. SEER cancer statistics review. Bethesda, MD: National Cancer Institute; 2015. p. 1975–2012. [2] DeCew AE, Hadler JL, Daley AM, Niccolai L. The prevalence of HPV associated cervical intraepithelial neoplasia in women under age 21: Who will be missed under the new cervical cancer screening guidelines? J Pediatr Adolesc Gynecol 2013;26:346–9. [3] Hariri S, Unger ER, Sternberg M, et al. Prevalence of genital human papillomavirus among females in the United States, the National Health and Nutrition Examination Survey, 2003–2006. J Infect Dis 2011;204:566–73. [4] Ho GY, Bierman R, Beardsley L, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998;338:423–8. [5] Castle PE, Schiffman M, Wheeler CM, Solomon D. Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol 2009;113:18–25. [6] Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol 2012;137:516–42. [7] Arbyn M, Kyrgiou M, Simoens C, et al. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: Meta-analysis. BMJ 2008;337:a1284. [8] Kyrgiou M, Koliopoulos G, Martin-Hirsch P, et al. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: Systematic review and meta-analysis. Lancet 2006;367:489–98. [9] Kyrgiou M, Valasoulis G, Stasinou SM, et al. Proportion of cervical excision for cervical intraepithelial neoplasia as a predictor of pregnancy outcomes. Int J Gynaecol Obstet 2015;128:141–7. [10] Acharya G, Kjeldberg I, Hansen SM, et al. Pregnancy outcome after loop electrosurgical excision procedure for the management of cervical intraepithelial neoplasia. Arch Gynecol Obstet 2005;272:109–12. [11] Noehr B, Jensen A, Frederiksen K, et al. Depth of cervical cone removed by loop electrosurgical excision procedure and subsequent risk of spontaneous preterm delivery. Obstet Gynecol 2009;114:1232–8. [12] Ciavattini A, Clemente N, Delli Carpini G, et al. Loop electrosurgical excision procedure and risk of miscarriage. Fertil Steril 2015;103:1043–8. [13] Bulletins—Gynecology ACoP. ACOG Practice Bulletin no. 109: Cervical cytology screening. Obstet Gynecol 2009;114:1409–20. [14] Moyer VA, Force USPST. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012;156:880–91, W312. [15] Hariri S, Unger ER, Powell SE, et al. The HPV vaccine impact monitoring project (HPV-IMPACT): Assessing early evidence of vaccination impact on
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27] [28]
[29]
[30] [31]
HPV-associated cervical cancer precursor lesions. Cancer Causes Control 2012;23:281–8. Bharel M, Lin WC, Zhang J, et al. Health care utilization patterns of homeless individuals in Boston: Preparing for Medicaid expansion under the Affordable Care Act. Am J Public Health 2013;103(Suppl. 2):S311–7. Thomas MR, Waxmonsky JA, Gabow PA, et al. Prevalence of psychiatric disorders and costs of care among adult enrollees in a Medicaid HMO. Psychiatr Serv 2005;56:1394–401. Bureau of Labor Statistics. Consumer Price Index: Measuring Price Change for Medical Care in the CPI. United States Department of Labor. April 12, 2010. Available at: https://www.bls.gov/cpi/factsheets/medical-care.htm. Accessed November 10, 2017. Hirth JM, Tan A, Wilkinson GS, Berenson AB. Compliance with cervical cancer screening and human papillomavirus testing guidelines among insured young women. Am J Obstet Gynecol 2013;209:200, e201-207. Summers SL, Petzel A, Anderson J, Kenton K. Cervical cancer screening rates in a chart review of adolescent patients at an Academic Institution before and after the publication of the 2009 American College of Obstetricians and Gynecologists’ Recommendations. J Pediatr Adolesc Gynecol 2015;28:258– 62. Tsui J, Hofstetter AM, Soren K. Cervical cytology screening among lowincome, minority adolescents in New York City following the 2009 ACOG guidelines. Prev Med 2014;63:81–6. Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007;197:346–55. Fauci JM, Schneider KE, Whitworth JM, et al. Referral patterns and incidence of cervical intraepithelial neoplasia in adolescent and pregnant patients: The impact of the 2006 guidelines. J Low Genit Tract Dis 2011;15:124–7. Wieland DL, Reimers LL, Wu E, et al. Performance of implementing guideline-driven cervical cancer screening measures in an inner-city hospital system. J Low Genit Tract Dis 2011;15:296–302. Kinney W, Hunt WC, Dinkelspiel H, et al. Cervical excisional treatment of young women: A population-based study. Gynecol Oncol 2014;132:628– 35. Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: A randomised controlled trial. Lancet 2004;364:1757–65. Markowitz LE, Liu G, Hariri S, et al. Prevalence of HPV after introduction of the vaccination program in the United States. Pediatrics 2016;137:1–9. Reagan-Steiner S, Yankey D, Jeyarajah J, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13–17 years—United States, 2014. MMWR Morb Mortal Wkly Rep 2015;64:784– 92. Cunningham P, Rudowitz R, Young K, et al. Understanding Medicaid Hospital Payments and the Impact of Recent Policy Changes The Henry J. Kaiser Family Foundation. 2016. Available at: https://www.kff.org/report-section/ understanding-medicaid-hospital-payments-and-the-impact-of-recent -policy-changes-issue-brief/. Accessed November 10, 2017. Nelb R, Teisl J, Dobson A, et al. For disproportionate-share hospitals, taxes and fees curtail Medicaid payments. Health Aff (Millwood) 2016;35:2277–81. Ursu A, Sen A, Ruffin M. Impact of cervical cancer screening guidelines on screening for Chlamydia. Ann Fam Med 2015;13:361–3.
www.jahonline.org Original article
Cervical Cancer Screening and Follow-Up Procedures in Women Age <21 Years Following New Screening Guidelines Alexandra M. Foxx, M.D. a, Yuwei Zhu, M.D., M.S. b, Edward Mitchel, M.S. c, Sayeh Nikpay, Ph.D., M.P.H. c, Dineo Khabele, M.D. d, and Marie R. Griffin, M.D., M.P.H. e,* a
Vanderbilt University School of Medicine, Nashville, Tennessee Department of Biostatistics Department of Health Policy d Department of Obstetrics and Gynecology e Departments of Health Policy and Medicine, Nashville, Tennessee b c
Article history: Received March 13, 2017; Accepted August 30, 2017 Keywords: Cervical cancer; Cervical dysplasia; Screening guidelines
A B S T R A C T
Purpose: The 2009 American College of Obstetricians and Gynecologists guidelines recommended no cervical cancer screening before age 21 years. We examined changes in screening, diagnostic, and treatment procedures for cervical dysplasia after guideline introduction, and cost implications. Methods: We studied Davidson County women aged 18–20 years, enrolled in Tennessee Medicaid, 2006–2014. We identified those with at least one Papanicolaou (Pap) test, human papillomavirus detection test, colposcopy, or excisional dysplasia treatment annually via Current Procedural Terminology coding. We used rate ratios with 95% confidence intervals to compare annual changes in procedure and treatment rates from 2014 to 2006. We counted total outcomes to estimate annual costs based on 2014 average procedural costs. Results: From 2006 to 2014, about 3,800 Davidson County women aged 18–20 years were enrolled in Medicaid annually. From 2006 to 2014, there were declines in Pap tests from 55.6 to 15.2 per 100 women (rate ratio .27, 95% confidence interval .25–.3); human papillomavirus tests from 13.8 to 5.9 per 100 (.42, .36–.5); colposcopy from 9.4 to 1.1 per 100 (.12, .08–.17); and dysplasia treatment from 1.1 to 0 per 100. The estimated cost of screening and procedures fell from $53 to $8 per enrolled woman, not accounting for changes in visits or complications associated with these procedures. Conclusions: The 2009 screening guidelines were associated with major declines in screening, diagnostic, and treatment procedures for cervical dysplasia. Minimum estimated procedure and treatment costs saved were $45 per enrolled woman age 18–20 years. © 2017 Society for Adolescent Health and Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
IMPLICATIONS AND CONTRIBUTION
Cervical cancer screening declined in young women aged 18–20 years since introduction of 2009 screening guidelines. From 2006 to 2014, Pap smears and colposcopies declined 73% and 88%, respectively, in young women enrolled in Tennessee’s Medicaid program. Results estimated a minimum cost savings of $45 per enrollee.
Conflicts of Interest: The authors have no conflicts of interest to disclose. Sources of study: Tennessee Bureau of TennCare of the Department of Finance and Administration provided the data. Disclosures: HPV IMPACT study was approved as public health surveillance and not research by CDC, Vanderbilt, and TN Department of Health IRBs, 45 CFR 164.512. * Address correspondence to: Marie R. Griffin, M.D., M.P.H., 1500 21st Ave S. Suite 2600, Nashville, TN 37215. E-mail address: Marie.griffi[email protected] (M.R. Griffin). 1054-139X/© 2017 Society for Adolescent Health and Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/). https://doi.org/10.1016/j.jadohealth.2017.08.027
ARTICLE IN PRESS 2
A.M. Foxx et al. / Journal of Adolescent Health ■■ (2017) ■■–■■
Invasive cervical cancer is very rare in women less than 21 years of age [1]; however, minor grade cytology abnormalities are common [2]. Cervical cancer typically results from infection with human papillomaviruses (HPVs). In the United States, genital detection of HPV infections increases through age 24 years and then gradually declines [3]. About 90% of these infections clear in the first two years after acquisition, with regression of accompanying dysplasia [4,5]. Cervical cancer screening modalities include Papanicolaou (Pap) tests to detect abnormal cells and HPV DNA testing to identify oncogenic HPVs [6]. When pre-cancerous lesions are detected, further evaluation may be warranted with colposcopy with or without biopsy. More invasive lesion excision procedures include cryotherapy, loop electrosurgical excision procedure (LEEP), laser ablation, and cold knife conization. Cervical cancer screening and subsequent treatments have significant immediate risks, including anxiety, stigmatization, pain, bleeding, and small bowel injury [6–10]. Systematic reviews of observational studies have found associations between some treatment procedures and perinatal mortality, preterm birth, low birth weight, premature rupture of membranes, and caesarean delivery [7,8]. Many women who undergo these procedures have other risk factors that independently put them at higher risk of adverse pregnancy outcomes. However, procedure-associated risks appear to be related to the amount and/or depth of tissue removed [9–11]. In addition, miscarriage has been associated with pregnancy timing within 12 months of LEEP procedures, but not later [12]. Given the potential for harms from screening and low risk of invasive cancer in very young women, in 2009, the American College of Obstetricians and Gynecologists recommended the initiation of cervical cancer screening at 21 years of age. In addition, they recommended reduced frequency of screenings in other age groups [13]. In 2012, the US Preventive Services Task Force released guidelines in agreement with those of the American College of Obstetricians and Gynecologists [14]. The first HPV vaccine was licensed in the United States in 2006 and recommended by the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices in 2007 for routine vaccination of girls age 11–12 years and catchup vaccination of females 13–26 years. We monitor the incidence of cervical dysplasia in Davidson County (Nashville) women aged 18–39 years as a participating site in CDC’s population-based surveillance, HPV-IMPACT [15], designed to evaluate the effectiveness of the HPV vaccination program on reducing cervical dysplasia incidence. Monitoring changes in screening is an important part of this evaluation. Given that screening is no longer recommended for women aged 18–20 years, we aimed to determine how screening has changed in this group of young women. Population-based data on screening were available for our County for women enrolled in Tennessee’s Medicaid Program (TennCare), which we used to estimate changes following the new screening guidelines. Materials and Methods We performed a retrospective study investigating cervical cancer screening in women 18–20 years of age, who were residents of Davidson County (Nashville), Tennessee, and enrolled in the Tennessee Medicaid program (TennCare). We determined the incidence of Pap smears, HPV DNA testing, colposcopy, and invasive cervical procedures from 2006 to 2014 to deter-
Table 1 Current Procedural Terminology (CPT) coding for specific study procedures Procedure
CPT codes
Pap testing
88141–88143, 88147, 88148, 88150, 8815288155, 88164–88167, 88174, 88175, G0123, G0124, G0141, G0143-G0145, G0147, G0148, P3000, P3001, Q0091 87621, 87623–87625 57420–57452, 57454–57456, 57460, 57461
HPV testing Colposcopy Invasive procedures LEEP/LETZ Cold knife Cryotherapy Ablation or cautery
57461, 57522 57520 57511 57513, 57510
mine the impact of the new cervical screening guidelines. Current procedural terminology codes (Table 1) were used to identify and enumerate the frequency of cervical cancer screening and treatment procedures as reflected in TennCare insurance data. The Tennessee Department of Finance and Administration Bureau of TennCare provided the data. This analysis was performed as part of the HPV-IMPACT study [15], a population-based surveillance of HPV-related disease, and thus considered public health surveillance and not human research by the CDC, Vanderbilt, and TN Department of Health institutional review boards. Davidson County, TN, is one of five HPV IMPACT sites that estimates population cervical cancer screening rates and incidence of cervical dysplasia. The denominator for rate calculations was the number of Davidson County women aged 18–20 years and enrolled in TennCare on July 1 of each year. This method gives an estimate of total person-years of women aged 18–20 years in the population. We counted the number of women with at least one Pap, HPV test, colposcopy, or invasive cervical treatment for dysplasia annually. We also counted total procedures, allowing at most one of each type of procedure per day for each woman enrolled. Screening and treatment procedures (numerators) and estimates of denominators were derived for all women, as well as for nonHispanic white, non-Hispanic black, and Hispanic women as classified in TennCare data. Women with another designation or unknown race or ethnicity were classified as “other.” There were no requirements for continuous enrollment in TennCare for women eligible for this study. We used rate ratios (RRs) to estimate the annual change in procedures performed through 2014 using 2006 as the reference year, and calculated 95% confidence intervals (CIs) using the delta method. We estimated total and average annual costs for all procedures in 2006 and 2014 using actual payments received by providers in the TennCare program. We also calculated overall median costs for each procedure. This approach is consistent with others using Medicaid-managed care data to estimate costs [16] [17]. We excluded all procedures with payments less than or equal to zero from the calculation. Costs were rounded up to whole values and expressed in 2014 dollars using the medical component of the 2006–2014 Consumer Price Index [18]. Results There were about 3,800 Davidson County women aged 18– 20 years enrolled in TennCare annually over the study period ranging from 3,565 women in 2007 to 4,150 women in 2011. The racial or ethnic distribution remained relatively stable, with overall
ARTICLE IN PRESS
Number of Women age 18-20 years
A.M. Foxx et al. / Journal of Adolescent Health ■■ (2017) ■■–■■
3
4500 4000 3500 3000 2500 2000 1500 1000 500 0 2006
2007
2008
2009
2010
2011
2012
2013
2014
Year Black, non-Hipanic
White non-Hispanic
Hispanic
Other
Figure 1. Annual enrollment in TennCare by race or ethnicity for Davidson County women aged 18–20 years, 2006–2014.
57% non-Hispanic black, 28.5% non-Hispanic white, 4.8% Hispanic, and 9.8% other or unknown. In 2014 compared with 2006, there were more women classified as Hispanic and Other and fewer as non-Hispanic black and white, as shown in Figure 1. The number of women aged 18–20 years in Davidson County who had a Pap smear fell from 2,057 in 2006 to 546 in 2014. Pap screening rates declined from 55.6 per 100 women in 2006 to 15.2 per 100 women in 2014 (RR .27, 95% CI .25–.3) (Figure 2A). Pap screening per 100 women declined >70% from 2006 to 2014 in black (from 52.3% to 15.2%), white (from 63.7% to 18.7%), and Hispanic (from 58.0% to 9.6%) women. The number of women undergoing other cervical cancer screening and diagnostic procedures also declined: HPV testing from 346 to 40; colposcopy from 512 to 211; and invasive procedures from 41 to 0. The annual rates of all screening and procedures declined: HPV testing from 13.8 to 5.9 per 100 (RR .42, 95% CI .36–.5), colposcopy from 9.4 to 1.1 per 100 (RR .12, 95% CI .08–.17), and dysplasia treatment from 1.1 per 100 women in 2006 to no events in 2014 (Figure 2B). Average annual costs (standard deviation) in 2014 dollars over the study period were $37.47 (27.93) for Pap tests, $68.14 (48.45) for HPV tests, $131.26 (271.80) for colposcopy, and $753.85 (860.00) for invasive procedures (Table 2). Median annual costs tended to be lower than average costs, because the latter may be influenced by high cost outliers. Median costs overall were $34.84 for Pap tests, $61.63 for HPV tests, $104.62 for colpos-
copy, and $302.15 for invasive procedures. Costs for the entire encounters in which these tests were performed were much higher: $346.80 (329.73) for Pap tests, $289.04 (324.53) for HPV tests, $249.18 (399.62) for colposcopy, and $1,705.15 (1,228.52) for invasive procedures. From 2006 to 2014 estimated annual costs for procedures alone in our cohort dropped from $195,646 to $30,285, an 85% decrease. The contribution of each procedure category to these costs is shown in Figure 3. Accounting for the changes in number of women enrolled per year, the cost fell from an estimated $53 to $8 per woman enrolled or an estimated $45 saved per enrolled woman. Discussion We found declines in all cervical cancer screening and treatment procedures in women aged 18–20 years between 2006 and 2014. Previous studies [19–21] have documented the decrease in Pap tests in young women since the introduction of the 2009 guidelines; however, these studies did not evaluate treatment procedures nor assess cost implications. Young women in our cohort experienced a 73% decline in annual cervical cancer screening with Pap tests from 2006 to 2014. Declines of >70% were observed for black, white, and Hispanic women. Pap test rates appeared stable from 2006 to 2009, and declined steadily thereafter, strongly suggesting that this change was in response to the 2009 guidelines. The guidelines also
Table 2 Estimated average cost and standard deviation (SD) in 2014 US dollars for cervical cancer screening and treatment procedures 2006–2014, Davidson County women aged 18–20 years enrolled in TennCare Pap test Year 2006 2007 2008 2009 2010 2011 2012 2013 2014 Average
Average 34.30 46.37 36.36 37.35 41.07 34.01 38.87 29.44 27.60 37.47
HPV test SD 34.74 27.99 22.65 26.12 32.11 23.27 26.61 20.90 14.99 27.92
Average 83.36 78.00 66.85 64.86 75.69 63.43 75.38 36.64 42.58 68.14
Colposcopy SD 58.74 42.91 35.81 38.36 60.96 43.97 56.06 30.88 28.32 48.45
Average 69.74 153.71 165.03 159.78 181.47 110.00 106.20 125.93 91.45 131.26
Invasive procedure SD 144.86 173.02 462.47 306.24 360.67 63.36 52.81 290.07 32.28 271.80
Average 722.15 653.5 908.92 701.71 1,109.81 504.32 120.57 2,108.70 0 753.85
SD 659.89 538.09 1,149.94 874.53 1,301.74 751.54 NA 2,691.33 NA 860.00
ARTICLE IN PRESS A.M. Foxx et al. / Journal of Adolescent Health ■■ (2017) ■■–■■
a
Annual Pap Tests per 100 Women
4
60 50 40 30 20 10 0 2006
2007
2008
2009
2010
2011
2012
2013
2014
Year
Annual Procedures per 100 Women
18 16 14 12 10 8 6 4 2 0 2006
2007
2008
2009
2010
2011
2012
2013
2014
Year
b
HPV test
Colposcopy
Invasive Procedure
Figure 2. (A) The number of women who received at least one Pap test per 100 Davidson County women aged 18–20 years enrolled in TennCare, by year 2006– 2014. (B) The number of women who received at least one HPV test, colposcopy, and invasive cervical procedure per 100 Davidson County women aged 18–20 years enrolled in TennCare, by year 2006–2014.
$250,000
$200,000
$150,000
$100,000
$50,000
$0 2006
2007 Pap test
2008 HPV test
2009
2010
Colposcopy
2011
2012
2013
2014
Invasive Procedure
Figure 3. Total costs for Pap tests, HPV test, colposcopy, and invasive procedures, Davidson County women aged 18–20 years enrolled in TennCare, by year 2006–2014.
ARTICLE IN PRESS A.M. Foxx et al. / Journal of Adolescent Health ■■ (2017) ■■–■■
recommended no HPV testing for women under 21 years of age. In our cohort, HPV testing was much less common than Pap tests (13.8 vs. 55.6 per 100, respectively) in 2006. However, even this already low incidence of HPV testing declined 57% over the study period. In this population of young women enrolled in TennCare, screening trends were similar for non-Hispanic white, nonHispanic black, and Hispanic women. It is unknown whether continued screening is confined to specific provider or patient populations. Given the continued decline in screening through 2014, practitioners who continue to screen will likely soon be rare. The decline in colposcopies and invasive cervical procedures appeared to begin before 2009. We expected that a decline in screening would result in parallel declines in colposcopies and invasive cervical procedures. Indeed, colposcopy decreased 88% from 9.4 to 1.1 per 100 women from 2006 to 2014, and no invasive cervical procedures were performed in this population in 2014. Although the 2009 guidelines may have resulted in an accelerated decline in colposcopies and invasive surgical procedures, the declines appeared to begin as early as 2006. In 2006, a consensus process composed of 146 experts representing 29 organizations and professional societies developed the American Society for Colposcopy and Cervical Pathology guidelines for the management of women with abnormal cervical cytology [22]. Fauci et al. found that the 2006 guidelines were associated with a decline in referrals of women with cytologic abnormalities categorized as atypical squamous cells of unknown significance to colposcopy [23]. Wieland et al. implemented algorithm-based protocols for triage to colposcopy to assure adherence to these guidelines, and prospectively tracked outcomes. During this intervention from 2006 to 2008, Pap tests changed little, but the number of colposcopy visits and biopsies declined. Notably, guideline-recommended care resulted in fewer cervical intraepithelial neoplasia 1 diagnoses but little change in cervical intraepithelial neoplasia 2 and 3 diagnoses [24]. Finally, Kinney et al. reported an 87% decline in LEEPs in women aged 15–20 years from 2007 to 2011, more modest declines in women 21–29 years, and no change in women 30– 39 years in New Mexico [25]. Changes in guidelines both for screening and for referral to colposcopy as well as HPV vaccine introduction may all have played a role in the large decline in colposcopies and invasive procedures in this age group. HPV vaccines were introduced in 2006 and approved by the US Food and Drug Administration for women 9–26 years old. By preventing acquisition of oncogenic HPVs 16 and 18, vaccination should decrease the incidence of cervical dysplasia, and the need for invasive procedures [26]. The uptake of HPV vaccine should not affect screening, but could affect colposcopy and invasive procedure rates. Vaccine is ideally given before onset of sexual activity, because it is ineffective for those already infected. Nationally, between 2003– 2006 and 2009–2012, representing time periods pre and post HPV vaccine introduction, the prevalence of HPV genotypes represented in the quadrivalent vaccine declined 63% in women 14–19 years, 34% in those 20–24 years, and not at all in women 25–34 years. The declines in HPV prevalence in young women were observed only in those with a history of vaccination, and were confined to HPV vaccine types, providing strong evidence of HPV vaccine impact among women younger than 25 years [27]. Thus, vaccination could have had a role in some of the trends observed in our population. However, vaccine uptake in Tennessee has been low, limiting the potential impact
5
on these trends. Vaccination of Tennessean girls, age 13–17 years with at least one dose of HPV vaccine was 47.8% in 2014, compared with the national uptake of 60.0% for all US girls age 13–17 years [28]. We estimated potential financial implications given the costs of the procedures we enumerated. We estimated, for women aged 18–20 years living in Davidson County enrolled in TennCare, an annual savings of $165,361 in procedural costs in 2014 compared with costs that would have accrued if rates of these procedures were the same as in 2006. Perhaps more compelling, when we account for the change in enrollment over this time period, we still observed the cost fell from an estimated $53 per woman to $8 per woman enrolled or an estimated $45 saved per enrolled woman. This estimate does not account for costs associated with the visit itself, the additional procedures performed at the visit, transportation costs, or other indirect costs. TennCare is a managed care program, thus savings from limiting procedures would accrue to individual managed care organizations rather than the State of Tennessee Medicaid Program. Our estimates of savings are conservative. It is likely that many but not all physician encounters would occur even if Pap and HPV tests were not performed. However, it is likely that there would be some decrease in these visits. However, costs of encounters for colposcopy and invasive procedures were two to three times that of the procedures themselves, and it is likely that many of these costs would also be saved. Potential savings would be higher in settings with higher rates of screening at baseline. Our study has several limitations. We relied on diagnostic and procedure coding to enumerate study screening and treatment outcomes. It is possible that diagnoses or procedures were missed or misclassified. Additionally, generalizability is limited, as all participants were enrolled in TennCare in a single county. This may restrict the relevance of this study to low-income persons in a small geographic area. Of note, private insurance was a strong predictor of cervical cancer screening in prior studies [20], suggesting the impact of the 2009 guidelines in a private insurance cohort could be more dramatic. Additionally, we had no information on knowledge of guidelines by providers. Finally, Medicaid has historically reimbursed providers below cost. Therefore, payments to providers may represent less than the full cost of providing care [29]. However, the difference between costs and payments has been narrowing over time [30]. In conclusion, the decline in cervical cancer screening and associated diagnostic and treatment procedures observed in this study is consistent with a strong impact of both the 2006 (management of cervical dysplasia) and the 2009 (screening) guideline recommendations. HPV vaccination may also have had a role in the decline in diagnostic and treatment procedures. Decreasing the frequency of unnecessary and harmful cervical cancer screening represents an area for cost savings and harm reduction. Although recommendations to delay screening in this age group will benefit most women, this delay may also result in progression of dysplasia in some women. There is evidence that the decline in screening for cervical cancer has resulted in declines in appropriate screening for other sexually transmitted diseases such as chlamydia [31]. These screening activities should be uncoupled. Ultimately, assuring uptake of HPV vaccine is the preferred way to prevent cervical cancer. It will be important to continue to monitor trends in both precancer and cancer in women aged 21 years and older during the HPV vaccine era.
ARTICLE IN PRESS 6
A.M. Foxx et al. / Journal of Adolescent Health ■■ (2017) ■■–■■
Acknowledgments This project was funded through Emerging Infections Cooperative Agreement 5U01C10003. We are indebted to the Tennesee Bureau of TennCare of the Department of Finance and Administration, which provided the data.
[16]
[17]
[18]
References [1] Howlader NNA, Krapcho M, Garshell J, et al. SEER cancer statistics review. Bethesda, MD: National Cancer Institute; 2015. p. 1975–2012. [2] DeCew AE, Hadler JL, Daley AM, Niccolai L. The prevalence of HPV associated cervical intraepithelial neoplasia in women under age 21: Who will be missed under the new cervical cancer screening guidelines? J Pediatr Adolesc Gynecol 2013;26:346–9. [3] Hariri S, Unger ER, Sternberg M, et al. Prevalence of genital human papillomavirus among females in the United States, the National Health and Nutrition Examination Survey, 2003–2006. J Infect Dis 2011;204:566–73. [4] Ho GY, Bierman R, Beardsley L, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998;338:423–8. [5] Castle PE, Schiffman M, Wheeler CM, Solomon D. Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol 2009;113:18–25. [6] Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol 2012;137:516–42. [7] Arbyn M, Kyrgiou M, Simoens C, et al. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: Meta-analysis. BMJ 2008;337:a1284. [8] Kyrgiou M, Koliopoulos G, Martin-Hirsch P, et al. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: Systematic review and meta-analysis. Lancet 2006;367:489–98. [9] Kyrgiou M, Valasoulis G, Stasinou SM, et al. Proportion of cervical excision for cervical intraepithelial neoplasia as a predictor of pregnancy outcomes. Int J Gynaecol Obstet 2015;128:141–7. [10] Acharya G, Kjeldberg I, Hansen SM, et al. Pregnancy outcome after loop electrosurgical excision procedure for the management of cervical intraepithelial neoplasia. Arch Gynecol Obstet 2005;272:109–12. [11] Noehr B, Jensen A, Frederiksen K, et al. Depth of cervical cone removed by loop electrosurgical excision procedure and subsequent risk of spontaneous preterm delivery. Obstet Gynecol 2009;114:1232–8. [12] Ciavattini A, Clemente N, Delli Carpini G, et al. Loop electrosurgical excision procedure and risk of miscarriage. Fertil Steril 2015;103:1043–8. [13] Bulletins—Gynecology ACoP. ACOG Practice Bulletin no. 109: Cervical cytology screening. Obstet Gynecol 2009;114:1409–20. [14] Moyer VA, Force USPST. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012;156:880–91, W312. [15] Hariri S, Unger ER, Powell SE, et al. The HPV vaccine impact monitoring project (HPV-IMPACT): Assessing early evidence of vaccination impact on
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27] [28]
[29]
[30] [31]
HPV-associated cervical cancer precursor lesions. Cancer Causes Control 2012;23:281–8. Bharel M, Lin WC, Zhang J, et al. Health care utilization patterns of homeless individuals in Boston: Preparing for Medicaid expansion under the Affordable Care Act. Am J Public Health 2013;103(Suppl. 2):S311–7. Thomas MR, Waxmonsky JA, Gabow PA, et al. Prevalence of psychiatric disorders and costs of care among adult enrollees in a Medicaid HMO. Psychiatr Serv 2005;56:1394–401. Bureau of Labor Statistics. Consumer Price Index: Measuring Price Change for Medical Care in the CPI. United States Department of Labor. April 12, 2010. Available at: https://www.bls.gov/cpi/factsheets/medical-care.htm. Accessed November 10, 2017. Hirth JM, Tan A, Wilkinson GS, Berenson AB. Compliance with cervical cancer screening and human papillomavirus testing guidelines among insured young women. Am J Obstet Gynecol 2013;209:200, e201-207. Summers SL, Petzel A, Anderson J, Kenton K. Cervical cancer screening rates in a chart review of adolescent patients at an Academic Institution before and after the publication of the 2009 American College of Obstetricians and Gynecologists’ Recommendations. J Pediatr Adolesc Gynecol 2015;28:258– 62. Tsui J, Hofstetter AM, Soren K. Cervical cytology screening among lowincome, minority adolescents in New York City following the 2009 ACOG guidelines. Prev Med 2014;63:81–6. Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007;197:346–55. Fauci JM, Schneider KE, Whitworth JM, et al. Referral patterns and incidence of cervical intraepithelial neoplasia in adolescent and pregnant patients: The impact of the 2006 guidelines. J Low Genit Tract Dis 2011;15:124–7. Wieland DL, Reimers LL, Wu E, et al. Performance of implementing guideline-driven cervical cancer screening measures in an inner-city hospital system. J Low Genit Tract Dis 2011;15:296–302. Kinney W, Hunt WC, Dinkelspiel H, et al. Cervical excisional treatment of young women: A population-based study. Gynecol Oncol 2014;132:628– 35. Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: A randomised controlled trial. Lancet 2004;364:1757–65. Markowitz LE, Liu G, Hariri S, et al. Prevalence of HPV after introduction of the vaccination program in the United States. Pediatrics 2016;137:1–9. Reagan-Steiner S, Yankey D, Jeyarajah J, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13–17 years—United States, 2014. MMWR Morb Mortal Wkly Rep 2015;64:784– 92. Cunningham P, Rudowitz R, Young K, et al. Understanding Medicaid Hospital Payments and the Impact of Recent Policy Changes The Henry J. Kaiser Family Foundation. 2016. Available at: https://www.kff.org/report-section/ understanding-medicaid-hospital-payments-and-the-impact-of-recent -policy-changes-issue-brief/. Accessed November 10, 2017. Nelb R, Teisl J, Dobson A, et al. For disproportionate-share hospitals, taxes and fees curtail Medicaid payments. Health Aff (Millwood) 2016;35:2277–81. Ursu A, Sen A, Ruffin M. Impact of cervical cancer screening guidelines on screening for Chlamydia. Ann Fam Med 2015;13:361–3.