Obstetrics & Gynecology:
Common Abnormal Results of Pap and Human Papillomavirus Cotesting: What Physicians Are Recommending for Management
Berkowitz, Zahava MSPH, MSc; Saraiya, Mona MD, MPH; Benard, Vicki PhD; Yabroff, K. Robin PhD, MBA
From the Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia; and the Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland.
Funding for this study was provided by the National Cancer Institute (contract N02-PC-51308), Centers for Disease Control and Prevention (interagency agreement Y3-PC-6017-01), and the Agency for Healthcare Research and Quality (interagency agreement Y3-PC-5019-01 and Y3-PC-5019-02).
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the National Cancer Institute.
Corresponding author: Zahava Berkowitz, MSPH, MSc, Epidemiology and Applied Research Branch, Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, 4770 Buford Highway, Mailstop K-55, Atlanta, GA 30341; e-mail: email@example.com.
Financial Disclosure The authors did not report any potential conflicts of interest.
OBJECTIVE: To evaluate the association between physician and practice characteristics and adherence to management guidelines to better understand the factors associated with different screening recommendations by primary care physicians.
METHODS: We used a cross-sectional nationally representative survey of 950 primary care physicians familiar with human papillomavirus (HPV) testing to assess adherence to management guidelines by analyzing responses to two clinical vignettes of a 35-year-old woman who had Pap and HPV tests results: 1) discordant (normal Pap and positive HPV) or 2) mildly abnormal (atypical squamous cells of undetermined significance Pap and negative HPV). Analyses included multivariable logistic regression.
RESULTS: For the discordant test results, 54.3% (95% confidence interval [CI] 51–57.6%) of physicians recommended both Pap and HPV testing in 6–12 months, adhering to management guidelines. For the mildly abnormal results, only 12.2% (95% CI 10–14.7%) had a guideline-adherent recommendation of Pap testing in 12 months with no HPV test. In multivariable analyses, no significant difference among physicians' specialties was observed for the discordant results. For the mildly abnormal results, physician specialty was associated with guideline adherence in which obstetrician–gynecologists had the highest percent of adherence (19.8%) compared with family and general practitioners (9.3%) and internists (11%) (P<.001).
CONCLUSION: Even for the most common abnormal results, many physicians reported recommendations that did not adhere to current management guidelines. Evidence-based interventions are needed to improve adherence to management guidelines for the newer HPV DNA test.
LEVEL OF EVIDENCE: III
Approximately 30 million women receive a Pap test every year, of which at least 1.4 million are abnormal.1 The Pap test is not perfect, however, and both false-negative and false-positive screening results are common.2 Introduction of oncogenic human papillomavirus (HPV) DNA testing to help stratify the risk of developing high-grade cervical intraepithelial neoplasia (CIN) and invasive cervical cancer has the potential to improve cancer detection at the same time as minimizing unnecessary follow-up testing.3 The most common and accepted use of HPV testing is to triage women with equivocal Pap results (atypical squamous cells of undetermined significance) who are HPV-positive to colposcopy. The American Society of Colposcopy and Cervical Pathology has published guidelines to help primary care physicians manage abnormal cytology and HPV test results4–6 that incorporate risk of cervical disease.7 In this study, we chose common abnormal results associated with different risks of developing high-grade CIN in the next 2 years, atypical squamous cells of undetermined significance Pap and negative HPV (low risk of CIN 3), and normal Pap and positive HPV (higher risk of CIN 3) to assess current management practices of primary care physicians. We used a national survey of primary care physicians and their self-reported practices and recommendations to assess their adherence to American Society of Colposcopy and Cervical Pathology management guidelines. We evaluated the association between physician and practice characteristics and adherence to management guidelines with the goal of better understanding the factors associated with different management screening recommendations by primary care physicians.
We used a cross-sectional nationally representative sample of primary care physicians, including family practice, general practice, obstetrics–gynecology, and internal medicine to assess cervical cancer screening recommendations and management of established and emerging technologies. The American Medical Association's Physician Masterfile, containing demographic characteristics of U.S. physicians, was used as the sampling frame. To obtain a representative sample of physicians' specialties, and potentially reducing sample variation, physicians were selected using a stratified random sample with the four specialties as the sampling strata. Physicians' selection was proportional to their specialty's representation in the U.S. physician population. The survey was conducted between September 2006 and May 2007 and was approved by the Institutional Review Board of WESTAT (http://www.westat.com) who conducted the survey and by the U.S. Office of Management and Budget. Further information about the sampling and survey design has been described elsewhere.8,9
A total of 1,212 physicians completed the survey with an overall response rate of 67.5%. We restricted our sample to 950 Pap test providers who recommended HPV testing for either screening or management. Our primary outcomes were responses to two clinical vignettes describing a 35-year-old woman: 1) who had a negative (ie, normal) Pap test and positive HPV test (discordant) or 2) who had Pap test result of atypical squamous cells of undetermined significance and a negative HPV test (mildly abnormal). Physicians provided separate recommendations for when the next Pap and the next HPV test should occur. Women with mildly abnormal test results have a 2% or lower risk of developing CIN 3 in the next 2 years. According to American Society of Colposcopy and Cervical Pathology guidelines, the optimal management of these women would be a repeat Pap test in 12 months with no additional HPV test, and this was our measure of guideline-adherent recommendation for the vignette of the mildly abnormal results. Women with discordant test results have a higher absolute risk of 2–10% of developing CIN 3 in the next 2 years. For this reason, the American Society of Colposcopy and Cervical Pathology recommended that the next follow-up occur in 6–12 months with both Pap and HPV tests in their 2003 guidelines. These guidelines were updated in 2006 to recommend that the next follow-up occur in 12 months with both Pap and HPV test. Because the revised American Society of Colposcopy and Cervical Pathology guidelines were not published until 2007, we chose to broadly define guideline-adherent recommendations for the discordant vignette as both Pap and HPV tests in 6–12 months.4–6
To identify potential factors associated with guideline-adherent recommendations, we examined physician demographics, practice characteristics, and screening beliefs and practices. Physician demographics included sex, race and ethnicity, year of graduation from medical school, board certification, and medical school affiliation. Practice characteristics included location (urban or rural), number of physicians in the practice, type of practice (single or multispecialty), whether the practice is using electronic medical records, and percentage of uninsured patients. We combined family practice and general practice physicians as was previously done in analyses of these data.8
Screening belief was measured with a question about agreement on whether HPV cotesting with Pap is more accurate than Pap testing alone in predicting cervical cancer. Screening practices were measured with Pap test volume (ie, number of Pap tests ordered or performed per month for average-risk women), the type of Pap test used (liquid or conventional cytology), HPV testing use (screening, management, or both), and whether their patients asked about HPV testing in the past 12 months. Physicians were also asked questions related to follow-up of abnormal results in their practice: 1) how atypical squamous cells of undetermined significance Pap and positive HPV results are managed (in office or referred); 2) whether they have a system to ensure that women are informed of their abnormal results; and 3) whether they have a system to track follow-up of abnormal results. Additionally, primary care physicians were asked if they would conduct HPV testing for abnormal Pap test results including atypical squamous cells of undetermined significance; atypical squamous cells, cannot rule out high grade; low-grade squamous intraepithelial lesion; high-grade SIL; and atypical glandular cells.
We compared physicians' characteristics, beliefs, and practices related to HPV and Pap testing by physician specialty and assessed differences with chi square statistics. We used the adjusted Wald F test to evaluate the association of physician and practice characteristics, management, and beliefs with each of the outcomes in both univariable and multivariable logistic regression analyses and presented the results in the multivariable analyses as adjusted percentages (called predicted margins).10 These adjusted percentages are derived from the logistic regression analysis. They are easy to interpret when comparing categories within the variables. Also, the values of the predicted margins are independent of the reference groups that are used in the logistic regression model. The multivariable models were initially fitted using variables that have previously been shown to be associated with screening guideline adherence.8,9 Additionally, we included novel variables describing system-related mechanisms and management of abnormal results, which we hypothesized to be associated with guideline adherence. We used the backward selection regression method, driven by a P value approach, to develop our final model while assessing changes in the covariates that remained in the model. We retained in our final models those variables significantly or borderline significantly associated with the outcome at P<.1, except for the variable physician specialty, which was included in all our models. Differences between categories within each adjusted variable were tested by general linear contrasts of the predicted margins. To prevent loss of information resulting from missing data on the timing of the next Pap and HPV tests, we assumed an unknown response if a physician reported information for one of the tests only (n=5 Pap and 118 HPV for the first vignette, and n=6 Pap and 127 HPV for the second vignette). The questionnaire did not include a possible response category for “I don't know” to the timing of the next Pap or HPV test. We excluded physicians with missing data for timing for both next Pap and next HPV tests (n=35 for the discordant results and n=34 for the mildly abnormal results). A sample weight, which accounted for nonresponse by sample strata, was assigned to each survey respondent. The branching algorithm CHAID (Chi Square Automatic Interaction Detection), with the variables age, sex, year of medical school graduation, specialty, and region available from the American Medical Association Masterfile for both respondents and nonrespondents, was used to adjust for survey nonresponse. The sampling weights were used in the calculations of population estimates and their 95% confidence intervals (CIs). The statistical analyses were conducted using SUDAAN 9.1 to account for the stratified sampling survey design and for nonresponse.
Our sample of physicians recommending Pap and HPV testing included 408 family practice and general practice health care providers, 318 obstetrician–gynecologists, and 224 internists. The majority of physicians were male, non-Hispanic white, board-certified, and not affiliated with a medical school (Table 1). Most physician and practice characteristics varied significantly by specialty. Obstetrician–gynecologists had higher participation in continuing medical education for cervical cancer screening in the past 3 years (85.4%) than family practice and general practice health care providers (66.2%) and internists (57.5%). Obstetrician–gynecologists and family practice and general practice health care providers were more likely than internists to practice in a single specialty setting. Internists and obstetrician–gynecologists were more likely to report that a smaller percentage of their patients were uninsured than family practice and general practice health care providers.
More than 80% of all physicians reported that HPV DNA testing with Pap is more accurate than Pap alone (Table 2). The majority of primary care physicians reported that they recommend using HPV tests to follow-up after an abnormal Pap test. Cervical cancer screening practices varied significantly by physician specialty. Obstetrician–gynecologists had the highest Pap test volume and were more likely to recommend HPV testing for both routine screening and as a follow-up for an abnormal test than family practice and general practice health care providers or internists. Obstetrician–gynecologists were more likely to order HPV testing for atypical squamous cells of undetermined significance (97.5%) than family practice and general practice health care providers (91.1%) and internists (84%). However, family practice and general practice health care providers and internists were much more likely to order HPV testing for other Pap test abnormalities, including atypical squamous cells, cannot rule out high grade, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion. Obstetrician–gynecologists were much more likely to manage women with atypical squamous cells of undetermined significance Pap and positive HPV results in their office (97.5%) than family practice and general practice health care providers (40.6%) or internists (15.4%). Additionally, obstetrician–gynecologists were more likely than family practice and general practice health care providers and internists to report patients asking about HPV testing in the past 12 months and to have a system to track patients who do not complete follow-up of abnormal results.
For the vignette describing a 35-year-old woman with discordant test results, 93.5% of physicians recommended having the next Pap test in 6–11 months or in 12 months (9.8% and 83.7%, respectively) according to guidelines. However, 26.3% of these physicians would not recommend the HPV test with the Pap (data not shown). Only 54.3% (95% CI 51–57.6%) of all physicians recommended the HPV test at the same time as the Pap, adherent with guidelines. Family practice and general practice health care providers had the highest percentage of guideline-adherent recommendations (57.7%) and obstetrician–gynecologists the lowest (49.3%) (Table 3; unadjusted covariate).
For a 35-year-old woman with mildly abnormal results, 69.7% of all physicians recommended having the next Pap in 12 months, adherent with guidelines. However, 69.4% of these physicians also recommended the HPV test at the same time as the Pap (data not shown). Only 12.2% (95% CI 10–14.7%) of all physicians recommended no HPV test with the next Pap, adherent with guidelines. Obstetrician–gynecologists had the highest percentage (20.3%) and family practice and general practice health care providers the lowest (8.8%) of guideline-adherent recommendations (Table 4; unadjusted covariate).
In multivariable analysis, the findings varied substantially depending on the abnormal result described in the vignette as presented in Tables 3 and 4. Table 3 describes the adjusted percentage of physicians who adhered to guidelines for the discordant screening results. More than half of primary care physicians had guideline-adherent recommendations for the next Pap and HPV tests. Adherence was significantly higher for physicians who were affiliated with a medical school, who had recently participated in continuing medical education for cervical cancer screening, who had a mechanism to inform patients of abnormal results, and who refer their patients with HPV-positive results and a recent Pap showing atypical squamous cells of undetermined significance to another practitioner.
Few primary care physicians had guideline-adherent recommendations for the vignette describing the mildly abnormal test results (Table 4). Adherence was significantly higher among obstetrician–gynecologists than family practice and general practice health care providers and internists (P<.01 respectively), female physicians, and board-certified physicians. Adherence was also higher among physicians in larger practices and lower among physicians who thought that HPV testing with the atypical squamous cells of undetermined significance is more accurate than atypical squamous cells of undetermined significance alone in predicting cervical cancer (P<.01).
In our study that evaluated adherence to American Society of Colposcopy and Cervical Pathology guidelines for management of abnormal screening results, we found that primary care physicians are not basing management recommendations on CIN 3 risk. Overall, physicians reported recommending more testing than endorsed by American Society of Colposcopy and Cervical Pathology guidelines.4–6 This is of concern because overuse of follow-up testing is expensive for the health care system and may not improve patient outcomes.11
For women with discordant results, the 2006 American Society of Colposcopy and Cervical Pathology guidelines extended the screening interval to 12 months, noting the high rate of HPV clearance.4,5 One of the main concerns raised about HPV cotesting is lower specificity, which could identify many women with discordant results who may be treated more aggressively than necessary.11 Studies in the United States and Europe report a range of 4–9% prevalence of women who have discordant results and require additional follow-up.12,13 In this analysis, physicians generally adhered to guidelines for managing women with discordant results for the Pap test, but not for the HPV test. Given these findings, evaluation of provider response to 2008 American Society of Colposcopy and Cervical Pathology guidance that includes type-specific option tests to further stratify risk among this discordant group14 will be important. We found that primary care physicians who agree that HPV DNA testing with Pap is more accurate than Pap alone are more likely to have guideline-adherent recommendations for the discordant results.
Guidelines endorse follow-up for mildly abnormal results with a Pap test at 12 months and no HPV test. However, we found that most primary care physicians would recommend managing women with these mildly abnormal results more aggressively. In contrast to the discordant results, providers who thought that HPV testing was more accurate with the Pap than the Pap alone were less adherent to these guidelines. Perhaps, the tendency to overprescribe the HPV test is related to “all or none” use of the HPV test. Additionally, the ease of conducting HPV testing on the same cervical sample used for liquid-based cytology may facilitate this practice. These findings may also reflect influence of financial factors such as reimbursement for services15 and patients' reluctance to accept what they might think is suboptimal management (equated with fewer tests); overall, 56% of physicians reported that their patients had asked about HPV testing in the previous 12 months.
This potential for test overuse also is reflected in the large percentage of physicians who reported ordering HPV testing with the Pap for higher-grade Pap test results (ie, low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion) for which the HPV test is not recommended. A similar finding was also reported in a study conducted in 2004.16 This potential overuse of HPV testing after higher-grade Pap test results indicates that efforts to improve management practices should address the spectrum of abnormal results.
No large difference was found between physician specialties in guideline adherence. This is surprising because obstetrician–gynecologists are expected to have more knowledge about HPV testing guidelines for both screening and management. However, atypical squamous cells of undetermined significance Pap tests currently require less frequent follow-up if they are HPV-negative than if no HPV testing was performed. This may represent a paradigm shift for all specialty types because annual testing was previously reserved for routine screening. Newer guidelines do not recommend that any HPV testing should occur more frequently than annually.4
How can adherence to guidelines be improved? Primary care physicians have many competing demands and may not be able to keep up with ongoing changes in guidelines.17 These guidelines, which have been published every 2 to 3 years, have grown in complexity and consist of more than 10 algorithms alone for management of abnormal cytology.18 A question that deserves further research is whether less frequent guideline changes might be more successfully adopted. Consideration should be given to simplifying guidelines, improving consistency, and ensuring use of evidence-based methodology. Equally important is considering reimbursement strategies that support guideline-adherent practices.
We found that primary care physicians with recent continuing medical education participation and those with a mechanism in their practice to inform patients of abnormal results were more likely to report guideline-adherent recommendations. Development of educational materials and accompanying system changes, including more widespread use of electronic medical records, to help clinicians choose among multiple options may be needed. Other strategies include risk assessment algorithms7 along with web-based decision analysis programs19 and reminder systems.20 Implementation of system changes based on collaboration with laboratories on order forms may improve guideline adherence. Currently, many diagnostic laboratories' forms include orders for liquid-based Pap with HPV with no mention of Pap results, or for HPV for higher-grade Pap test abnormalities such as atypical squamous cells, cannot rule out high grade, low-grade squamous intraepithelial lesion, or high-grade squamous intraepithelial lesion. Development and evaluation of interventions that include educational components and corresponding test ordering system changes will be important for future research.
Although we used a large national population-based sample of primary care physicians with a high survey response rate, our study has several limitations. The survey relies on self-reports of screening practice and has not been validated with other data sources. However, a recent study suggests that physician self-report of practice, especially when using clinical vignettes, is reliable.21 Our patient vignettes may not reflect the diversity of women seen in practice, but they describe test results in which Pap and HPV tests are most commonly used and are endorsed by the American Society of Colposcopy and Cervical Pathology. There is also a possibility of selection bias toward those that use HPV testing in their practice and thus are most likely to be aware of the latest guidelines. However, our findings suggest that had we asked all health care providers (regardless of their familiarity with HPV testing) these questions, adherence to guidelines would be lower. Another concern is the potential for nonresponse bias. However, our sample weights incorporated an adjustment for nonresponse based on variables in the American Medical Association Physician Masterfile. Furthermore, the high response rate minimizes the potential impact for any unmeasured differences between respondents and nonrespondents.
In summary, our study adds to a growing body of research indicating that physician recommendations for cervical cancer screening and management of abnormal findings often do not adhere to current evidence-based guidelines. Our findings suggest that development and evaluation of interventions to improve adherence to management guidelines for the newer HPV DNA test, including educational efforts, reminder systems, and changes in test ordering systems will be important areas for additional research.
1. Saraiya M, McCaig LF, Ekwueme DU. Ambulatory care visits for Pap tests, abnormal Pap test results, and cervical cancer procedures in the United States. Am J Manag Care 2010;16:e137–44.
2. Siebers AG, Klinkhamer PJ, Grefte JM, Massuger LF, Vedder JE, Beijers-Broos A, et al. Comparison of liquid-based cytology with conventional cytology for detection of cervical cancer precursors: a randomized controlled trial. JAMA 2009;302:1757–64.
3. Saslow D, Runowicz CD, Solomon D, Moscicki AB, Smith RA, Eyre HJ, et al; American Cancer Society. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 2002;52:342–62.
4. Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D; 2006 ASCCP-Sponsored Consensus Conference. 2006 consensus guidelines for the management of women with abnormal cervical screening tests. J Low Genit Tract Dis 2007;11:201–22.
5. Wright TC Jr, Schiffman M, Solomon D, Cox JT, Garcia F, Goldie S, et al. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gynecol 2004;103:304–9.
6. Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ; ASCCP-Sponsored Consensus Conference. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA 2002;287:2120–9.
7. Castle PE, Sideri M, Jeronimo J, Solomon D, Schiffman M. Risk assessment to guide the prevention of cervical cancer. J Low Genit Tract Dis 2008;12:1–7.
8. Yabroff KR, Saraiya M, Meissner HI, Haggstrom DA, Wideroff L, Yuan G, et al. Specialty differences in primary care physician reports of papanicolaou test screening practices: a national survey, 2006 to 2007. Ann Intern Med 2009;151:602–11.
9. Saraiya M, Berkowitz Z, Yabroff KR, Wideroff L, Kobrin S, Benard V. Cervical cancer screening with both human papillomavirus and Papanicolaou testing vs Papanicolaou testing alone: what screening intervals are physicians recommending? Arch Intern Med 2010;170:977–85.
10. Graubard BI, Korn EL. Predictive margins with survey data. Biometrics 1999;55:652–9.
11. Sawaya GF. Adding human papillomavirus testing to cytology for primary cervical cancer screening: shooting first and asking questions later. Ann Intern Med 2008;148:557–9.
12. Castle PE, Fetterman B, Poitras N, Lorey T, Shaber R, Kinney W. Five-year experience of human papillomavirus DNA and Papanicolaou test cotesting. Obstet Gynecol 2009;113:595–600.
13. Datta SD, Koutsky LA, Ratelle S, Unger ER, Shlay J, McClain T, et al. Human papillomavirus infection and cervical cytology in women screened for cervical cancer in the United States, 2003–2005. Ann Intern Med 2008;148:493–500.
14. American Society for Colposcopy and Cervical Pathology. 2009 algorithm: use of HPV genotyping to manage HPV HR positive/cytology negative women 30 years and older. Available at: www.asccp.org/consensus.shtml
. Retrieved May 7, 2010.
15. Holland-Barkis P, Forjuoh SN, Couchman GR, Capen C, Rascoe TG, Reis MD. Primary care physicians' awareness and adherence to cervical cancer screening guidelines in Texas. Prev Med 2006;42:140–5.
16. Irwin K, Montano D, Kasprzyk D, Carlin L, Freeman C, Barnes R, et al. Cervical cancer screening, abnormal cytology management, and counseling practices in the United States. Obstet Gynecol 2006;108:397–409.
17. Yarnall KS, Pollak KI, Ostbye T, Krause KM, Michener JL. Primary care: is there enough time for prevention? Am J Public Health 2003;93:635–41.
19. Longhurst C, Turner S, Burgos AE. Development of a Web-based decision support tool to increase use of neonatal hyperbilirubinemia guidelines. Jt Comm J Qual Patient Saf 2009;35:256–62.
20. Baron RC, Melillo S, Rimer BK, Coates RJ, Kerner J, Habarta N, et al; Task Force on Community Preventive Services. Intervention to increase recommendation and delivery of screening for breast, cervical, and colorectal cancers by healthcare providers a systematic review of provider reminders. Am J Prev Med 2010;38:110–7.
21. Veloski J, Tai S, Evans AS, Nash DB. Clinical vignette-based surveys: a tool for assessing physician practice variation. Am J Med Qual 2005;20:151–7.
This article has been cited 2 time(s).
Jama Internal MedicineCervical Cancer Screening Intervals, 2006 to 2009: Moving Beyond Annual TestingJama Internal Medicine
Journal of the American Medical Informatics AssociationFormative evaluation of the accuracy of a clinical decision support system for cervical cancer screeningJournal of the American Medical Informatics Association
© 2010 The American College of Obstetricians and Gynecologists
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Looking for ABOG articles? Visit our ABOG MOC II collection. The selected Green Journal articles are free through the end of the calendar year.
ACOG MEMBER SUBSCRIPTION ACCESS
If you are an ACOG Fellow and have not logged in or registered to Obstetrics & Gynecology, please follow these step-by-step instructions to access journal content with your member subscription.
Data is temporarily unavailable. Please try again soon.
Readers Of this Article Also Read