American Journal of Obstetrics & Gynecology
Volume 197, Issue 4 , Pages 356.e1-356.e6, October 2007

Risk assessment to guide the prevention of cervical cancer

  • Philip E. Castle, PhD, MPH

      Affiliations

    • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD
    • Corresponding Author InformationReprints: Philip E. Castle, PhD, MPH, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Room 5004, MSC 7234, Bethesda, MD 20892-7234
    • ,
  • Mario Sideri, MD

      Affiliations

    • Preventive Gynecology Unit, European Institute of Oncology, Milan, Italy.
    • ,
  • Jose Jeronimo, MD

      Affiliations

    • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD
    • ,
  • Diane Solomon, MD

      Affiliations

    • Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD
    • ,
  • Mark Schiffman, MD, MPH

      Affiliations

    • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD

Received 19 March 2007; received in revised form 31 May 2007; accepted 29 July 2007.

Article Outline

Advances in screening and diagnosis make it increasingly possible to prevent cervical cancer. However, if misused or poorly understood, these new tools will only increase costs and potentially harm patients without benefit. As a framework for standardized care that maximizes patient safety and well-being, we propose that a risk model be adopted to guide clinical management now and in the future. The model would use thresholds of increasing risk for cervical precancer and treatable cancer to guide clinical decision making for screening intensity, diagnostic evaluation, or treatment. Experts would decide on these risk thresholds and stratum based on the patient risk to benefit, independent of current (eg, cytology, carcinogenic HPV testing, and colposcopy) and future methods of measuring risk. A risk management model for cervical cancer prevention, based on appropriate clinical actions that correspond to risk stratum, can result in better allocation of resources to and increased safety for women at the greatest risk and increased well-being for women at the lowest risk.

Key words: biopsy, carcinogenic human papillomavirus, cervical cancer, cervical cytology, cervical precancer, colposcopy, human papillomavirus vaccination, loop electrosurgical excision procedure, Papanicolaou smears, risk

 

With the introduction of multiple new, promising screening and diagnostic tests, we are more capable of preventing cervical cancer and more precisely characterizing a woman’s risk for cervical cancer. However, we must devise new rational management strategies to avoid confusion among clinicians facing unfamiliar combinations of test results and provide optimal consistent care for women. For example, consider the following management scenarios. Patient A has low-grade squamous intraepithelial lesion (LSIL) cytology followed by a colposcopically directed biopsy showing cervical intraepithelial neoplasia (CIN) grade 1. Patient B has atypical squamous cells of undetermined significance (ASC-US) cytology, a positive triage carcinogenic human papillomavirus (HPV) test that sends her to colposcopy, at which time no abnormality is identified. How should each of these women be managed? Some clinicians might consider treatment for the “histologically confirmed CIN” of patient A but watchful waiting for patient B. In fact, both women are at the same risk of detection of CIN3/cancer (10-15%) within the subsequent 2 years. Clinicians must understand the implications of various test combinations in terms of a woman’s risk for CIN3/cancer, and given the same risk, it is logical and important to consider the same management strategy.

As another illustration that affects millions in the United States yearly, when should women who have ASC-US cytology but are carcinogenic HPV deoxyribonucleic acid (DNA) negative on triage be reexamined? As recently recognized by the American Society for Colposcopy and Cervical Pathology (ASCCP) Consensus Conference experts,1 their risk of subsequent CIN3/cancer is less than 2% over the following 2 years,2 no more than the risk among women with negative Papanicolaou tests (whose carcinogenic HPV status is unknown). Testing carcinogenic HPV negative identifies the half of ASC-US that represents benign look-alikes. Thus, routine screening interval is appropriate.

The general point is this: as new technologies are introduced, confusion will result unless there is an underlying logic to what we do with increasing knowledge about our patients. We propose that as an organizing principle it is reasonable to use risk for detecting CIN3/(treatable) cancer until the next scheduled screening visit as the metric to determine how often and how intensively to follow-up or treat patients, such that comparable risk leads to comparable interventions.

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Background 

Traditionally, the Papanicolaou smear or other cytologic method has been used as the primary test for cervical cancer screening programs. A positive cytologic result led to colposcopic evaluation and directed biopsy of apparent lesions. In turn, a biopsy diagnosed as CIN2 or worse (CIN2 or greater), or sometimes CIN1, led to treatment. Repetition of the cytology/colposcopy-based program has led to substantial decreases in cervical cancer rates in countries that have sufficient resources to sustain a high-quality, organized program.3

Each step in this process—cytology,4 colposcopy,5 and histology6—has limitations in terms of sensitivity and specificity for our target for treatment: CIN3/cancer (we will refer to CIN3 as the best surrogate of invasive cancer risk). To compensate for such test limitations, we have relied on repeated screening on an annual or biennial basis. In addition, we have used CIN2 as a threshold for treatment to provide an additional margin of safety, even though many CIN2 lesions are destined to regress.7 The addition of more accurate methods of screening and diagnosis could increase both the sensitivity and efficiency of the process by decreasing the number of repetitions needed to achieve programmatic efficacy. However, the addition of new tests will raise questions about the appropriate management of a positive result.

The ASCCP guidelines1 highlight an expanded role for the detection of carcinogenic HPV DNA in the clinical management of women with cervical abnormalities. Specifically, these guidelines recommend the use of HPV assays for the following: (1) reflex testing or “triage” for equivocal cytology (ie, ASC-US); (2) postcolposcopic follow-up of women with abnormal cytology found not to have CIN2 or greater; and (3) posttreatment follow-up to assess the risk of recurrence. In addition, carcinogenic HPV testing as an adjunct to cytology in primary cervical cancer screening of women 30 years old and older is now accepted,8 and there may be a future clinical role for HPV genotyping to identify HPV16 and HPV18, the 2 riskiest types of HPV.9 The introduction of carcinogenic HPV testing into clinical practice is based on the necessary role of persistent carcinogenic HPV infections in the development of cervical precancer and cancer.10 The clinical rationale is the already proven increased sensitivity of carcinogenic HPV4 testing for detection of cervical precancer and cancer and its greater reliability than cytology.6, 11 Carcinogenic HPV testing has been introduced to increase the efficiency of cervical cancer screening by better risk stratification than cytology alone.

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Risk Stratification 

The concept of risk stratification (distinguishing the few women at risk from the many who are not at risk) is the principle underlying any screening test. With regard to carcinogenic HPV DNA testing, finding carcinogenic types in cervical specimens does not provide a diagnosis of CIN3 or cancer; rather, it identifies a group of women among whom CIN3/cancer is more likely. Complementary tests may provide even more powerful risk stratification. For example, cytologically normal women who test negative for carcinogenic HPV have a very low risk of cervical precancer for the next 5-10 years12, 13 and are at virtually no risk of developing frank cancer. Conversely, women who have high-grade squamous intraepithelial lesion (HSIL) cytology, a positive test for carcinogenic HPV, and a colposcopic impression of high-grade cervical neoplasia have an 80% likelihood of having CIN3 or worse within 2 years14; even if these women are biopsied and not immediately found to have CIN2 or greater, they are still at greater than 60% risk of CIN3 or greater within the next 2 years.15

Algorithms based on specific interventions or tests, including cytologic interpretations, biopsy findings, or HPV testing may become outdated as technology evolves. HPV testing could be supplanted in the future by even more sophisticated molecular tests that measure the interaction of virus and human host. Also, HPV vaccination will affect all parts of cervical cancer prevention, although not eliminating the need for some kind of screening. Thus, it is rational to make clinical decisions based on the knowledge of the risk of precancer (ie, CIN3), which can be estimated for various test results and combinations of test results in prospective studies and clinical trials. Clinical algorithms, with agreed-upon a priori thresholds, would then apply for any new clinically validated16 test or diagnostic assay with well-documented risk associated with a positive or negative result.

Careful emphasis on risk, rather than procedure, would clarify many points of confusion. For example, the emphasis on histologic grading, which is unreliable,6 would decline in favor of more predictive endpoints. Most CIN1 diagnoses follow ASC-US or LSIL cytology. More rarely, CIN1 diagnoses follow HSIL cytology and may represent a higher risk for CIN3 or greater. However, the risk associated with all CIN1, without regard for the preceding cytologic results, will be less than for LSIL cytology. Many practitioners do not realize that a biopsy-derived diagnosis of CIN1 carries a lower risk than LSIL cytology or even carcinogenic HPV-positive ASC-US cytology (nota bene, LSIL, and HPV-positive ASC-US carry the same risk of CIN3 or greater17) because CIN1 implies that colposcopic biopsy has ruled out the most evident precancerous lesions.17 Whereas cytologic LSIL is a reliable sign of HPV infection,17 a histologic diagnosis of CIN1 is especially nonreproducible6 and lacks the predictive utility to decide management options.17 In addition, CIN2 should be seen as an equivocal finding predicting an elevated “risk” of cancer arising somewhere in the cervical transformation zone, not necessarily within that lesion.

We treat (excise with loop electrosurgical excision procedure [LEEP]) the entire transformation zone, not focal lesions, because biopsies showing CIN2 or even CIN3 indicate that the field of epithelium is at risk of cancer. CIN2 is also poorly reproducible6 and often nothing more than a sign of acute HPV infection upon review.18 So treatment, especially for CIN2, might be more accurately viewed as a cancer risk–reducing intervention.

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Risk Thresholds 

Professional clinical societies and cancer prevention experts together will make the decisions as to the proper clinical responses to which risk levels, considering benefits as well as total cost, which includes financial and negative health consequences. It is worth discussing to what extent protocols versus individual clinician judgment should dictate which tests are used, when, and how they should be interpreted. In general, we believe, because screening is inherently a population-wide intervention among predominantly well women, the costs and benefits of a screening test or program should be described on a population basis. For example, the number of cases of disease or death averted and the total cost, most importantly including iatrogenic consequences of unnecessary medical interventions should be summed over all women receiving the test. Evaluation of women with abnormal screening results, decisions on treatment, and proper posttreatment follow-up require increasing degrees of individualization and clinical judgment as risk becomes more clearly defined.

Basically, there are currently 4 options for management: (1) routine screening interval; (2) more intensive follow-up with shorter interval to rescreening; (3) colposcopy and biopsy; and (4) treatment. To promote discussion, we can provide some possible thresholds for risk of CIN3/cancer, as shown in the Table and illustrated in Figure 1, which are based on the examples from currently used management strategies. Given that there is no such thing as zero risk, the first principle is to acknowledge that there is an acceptable low level of risk that does not trigger more intensive follow-up.

TABLE. A table of cervical precancer risk based on current screening and management tools with proposed clinical follow-up
Stage of screening or clinical managementCytology resultsCarcinogenic HPV test results (HPV positive or HPV negative)ReferencesProposed clinical follow-upAbsolute risk of precancer (CIN3)⁎
ScreeningNegativeHPVnegative12, 13Routine2% or less
Screening/triageASC-USHPVnegative2
After colposcopy† HPVnegative15
ScreeningNegativeHPVpositive12, 1312months2% to less than 10%
ScreeningLSILHPVnegative27
ScreeningASC-US 27
After colposcopy†NegativeHPVpositive15
LEEP 28
Screening/triageASCUSHPVpositive29Colposcopy10% or greater
ScreeningLSIL 17
After colposcopy† HPVpositive15
Post-LEEPASC-US or greater (or)HPVpositive28
ScreeningHSIL 14Colposcopy/treatment?40% or greater
After colposcopy†HSIL 15Treatment?40% or greater
CIN2 biopsy 18Treatment
Colposcopy (high grade)HSILHPV+14Treatment?60% or greater

⁎Risk until the next screening.

†Cytology and HPV results are those from the first follow-up visit 6 months after colposcopy.

  • View full-size image.
  • FIGURE 1. 

    Risk of cervical precancer and results of screening and clinical management for cervical cancer prevention

  • A graphical representation of the risk of cervical precancer at different stages and results of screening and clinical management for cervical cancer prevention. The risks for each stage and result are approximate risks for CIN3 within a screening interval. The axis to the right of the figure represents increasing risk, from nearly 0% (blue) to 100% (red), of cervical precancer on a log scale. Each stage of screening and clinical management is represented by a different pattern, with the arrows at the bottom indicating the sequence of the stages. Number sign indicates that less than half of the cases of CIN2 on biopsy are subsequently diagnosed as CIN3 on excisional tissue (precancer). Dagger indicates time within a screening interval. Asterisk indicates test results at the next follow-up visit (6 months or longer).

  • Castle. Risk assessment for prevention of cervical cancer. AJOG 2007.

Women with a less than 2% risk of precancer within the subsequent 2-3 years (eg, women who test carcinogenic HPV negative in routine screening) might be at an acceptable low risk to remain in regular interval screening. Regular screening may include 1- to 2-year screening with cytology alone or every 3 years with cytology and carcinogenic HPV cotesting for women 30 years old and older. Women with a 2% to less than 10% risk (eg, women with negative cytology who test carcinogenic HPV-positive in screening or women with ASC-US cytology unqualified by carcinogenic HPV testing) might warrant rescreening in a year. Women with a 10% or greater risk (eg, women with LSIL cytology or carcinogenic HPV-positive ASC-US) may warrant immediate colposcopic evaluation including multiple biopsies to maximize the sensitivity of colposcopy in high-risk women.19

More controversial, women identified with a risk of precancer above a certain threshold may warrant treatment, even if an initial colposcopic evaluation and directed biopsy does not identify a precancerous lesion on that day. Treatment of risk may be justified at some thresholds because we now better appreciate the limitations in the sensitivity of colposcopy for finding precancerous lesions.5 There are legitimate concerns regarding a strategy of treatment based on risk that would lead to overtreatment of some women. In principle, we should recognize that the current treatment threshold of CIN2 already results in significant overtreatment of many women whose lesions would regress spontaneously; we accept this overtreatment to provide a margin of safety against misclassification of diagnosis and risk.

Importantly, some women may be more likely to be lost to follow-up and, given high risk, may benefit from treatment before the confirmation of disease.20 For example, women with HSIL cytology are still at a 40% or greater risk of having a precancerous lesion, even if the initial colposcopy is negative.15 Thus, in those populations in which loss to follow-up for colposcopy and treatment is a real concern, immediate treatment of women with HSIL cytology may be warranted to provide safety.20 Older women at high risk of precancer, for whom the potential adverse effects of treatment on fertility21 are not a consideration, may benefit from treatment without colposcopic confirmation because precancerous lesions tend to be higher in the endocervical canal and therefore more easily missed by colposcopy.

As described above, in the extreme, a combination of testing positive for carcinogenic HPV or HSIL cytology and having a colposcopic impression of high grade carries an approximately 80% risk of CIN3 or greater. The question becomes whether colposcopically directed biopsy, a flawed diagnostic procedure, provides any added information. With informed decision making between patient and clinician that takes into account patient well-being, it may be more cost effective and less invasive to immediately treat women with very high-risk profiles than to require 2 or more clinical visits including an intensive follow-up with multiple biopsies to find the precancerous lesion and then treat.

Accepted thresholds for deciding who needs closer surveillance, colposcopy, and treatment will aid in clinical decisions regarding any new validated test or diagnostic procedure. A new assay that yields a positive result with defined clinical risk will trigger action consistent with that risk. Thus, detection of new biomarker X by a laboratory- and clinically validated assay Y,16 which carries a 15% risk of CIN3/cancer in 2 years should be managed identically as LSIL cytology for which colposcopic evaluation is currently recommended.

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The Importance of Context in Clinical Decisions 

Context is another element that figures into the risk predicted by a particular set of clinical test results. A risk associated with a positive test, like a carcinogenic HPV DNA test or CIN2 biopsy, is situational. An illustrative example is as follows: young women who have recently become sexually active have a high prevalence of carcinogenic HPV but an extremely low prevalence of precancerous lesions. In fact, the positive predictive value of a carcinogenic HPV test is so low in these women that its use in screening is not recommended. By comparison, HPV prevalence drops and the prevalence of precancerous lesions rises in women who are 10-15 years after sexual debut, and its use is now recommended as a cotest with cytology in women 30 years old and older in the United States (median age of sexual debut is approximately 17 years22).

Another example is the risk of precancer following an ASC-US cytology in screening (2% to less than 10%) vs post-LEEP (10% or greater), which should trigger different clinical responses for each. Thus, the circumstances for the test result must be considered (eg, prior colposcopy, prior treatment, or HPV vaccination) to accurately project the risk and the appropriate clinical response. Figure 2 illustrates the principles of risk stratification and contextual use of a test.

  • View full-size image.
  • FIGURE 2. 

    Cumulative incidence of precancer

  • The figure shows the cumulative incidence of precancer (CIN3) and cancer (CIN3 or greater) by HPV status9, 12 and illustrates two aforementioned outlined principles: risk stratification and contextual use of a test. A positive test for carcinogenic HPV in women 30 years old and older even with negative cytology can identify those women at risk of precancer and cancer. More importantly, those who tested negative are at an extremely low risk over many years12 and should not be screened again for several years; the current screening recommendation is that women who are cytology and carcinogenic HPV negative should not be rescreened before 3 years.8 If the positive carcinogenic HPV test is then triaged using HPV16 and HPV18 detection, there is further risk stratification, with HPV16-positive or HPV18-positive women being at an extremely high risk of developing precancer or cancer.9 In fact, this risk was greater than the risk observed for women with LSIL, for whom colposcopy is recommended. Thus, when a validated HPV genotyping assay becomes available, colposcopy for HPV16-positive or HPV18-positive, cytology-negative women may be warranted. However, the appropriate management for HPV16-negative/HPV18-negative, carcinogenic HPV-positive, cytology-negative women becomes less clear because the absolute risk is low, yet these women still remain at risk for the 30% of the cancer not caused by HPV16 and HPV18. This clinical conundrum will become more common to screening of women 10-15 years after they have received vaccination against HPV16 and HPV18 infections.30 Thus, the risk of cervical precancer and cancer among women who test positive for carcinogenic HPV will differ between those who have and have not been previously vaccinated. (n.b., the X-axis does not represent continuous time and the time points represent midpoints within a follow-up time period. Follow-up time was crudely divided into an initial period of 0-9 months (Papanicolaou smears that were rapidly repeated, presumably prompted by a previous cytologic abnormality or suspicious symptoms), followed by yearly intervals for a total time of 122 months. These intervals roughly paralleled the intervals at which women returned for annual smears9).

  • Castle. Risk assessment for prevention of cervical cancer. AJOG 2007.

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Final Comments 

We emphasize that it is critical when accepting a risk-based model for cervical cancer prevention to acknowledge that a minimally acceptable risk of precancer should be defined to avoid the overscreening and overtreatment of women in an attempt to achieve the unachievable: perfect sensitivity prevention. In addition to the almost certain negative consequences of an overly aggressive cervical cancer prevention program, including the impact on fertility,21 the number of cancers spared in the United States, where the standardized incidence rates are less than 5.0 per 100,000,23 would be incremental and the costs to achieve it would sky-rocket above the billions already spent annually on cervical cancer screening.24 In some ways, such an attempt would be analogous to screening for vaginal cancer, which is caused by carcinogenic HPV but is extremely rare.23 Unfortunately, inappropriate screening of hysterectomized women who are only at risk for vaginal cancer still occurs.25

In summary, we have unprecedented capability to identify women at the greatest and lowest risk of cervical precancer and cancer using current and soon-to-be-available prevention tools. Our capacity to accomplish this is much more robust than the extensively cited and used model for breast cancer risk by Gail et al26 because we can now or will soon be able to ascribe risks of cervical precancer ranging from less than 1% to over 90% risk.

Given the moderate sensitivity of colposcopy/colposcopically directed biopsy to identify women with precancer5 and the availability of more objective tools to measure the risk, we suggest that a change of paradigm is in order: identify and manage based on aggregate risk for CIN3/precancer. Importantly, as we shift from a model with false certainty based on a colposcopic impression and diagnosis to a model of relative and absolute risk with acknowledged uncertainties, we will protect clinicians from medicolegal consequences for a highly successful but imperfect intervention. A risk management model for cervical cancer prevention, based on clinical actions corresponding to risk stratum, can result in better allocation of resources to and increased safety for women at the greatest risk and increased well-being for women at the lowest risk.

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References 

  1. Wright TC, 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 cancer screening tests. Am J Obstet Gynecol. 2007;197:346–355
  2. Safaeian M, Solomon D, Wacholder S, Schiffman M, Castle PE. Risk of pre-cancer and follow-up management strategies for women with HPV-negative ASCUS. Obstet Gynecol. 2007;109:1325–1331
  3. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108
  4. Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos G, Dillner J. Clinical applications of HPV testing: a summary of meta-analyses. Chapter 9 Vaccine. 2006;24(Suppl 3):S78–S89
  5. Jeronimo J, Schiffman M. Colposcopy at a crossroads. Am J Obstet Gynecol. 2006;195:349–353
  6. Stoler MH, Schiffman M. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA. 2001;285:1500–1505
  7. ASCUS-LSIL Triage Study (ALTS) Group. A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations. Am J Obstet Gynecol. 2003;188:1393–1400
  8. Wright TC, Schiffman M, Solomon D, et al. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gynecol. 2004;103:304–309
  9. Khan MJ, Castle PE, Lorincz AT, et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst. 2005;20:1072–107997
  10. Wright TC, Schiffman M. Adding a test for human papillomavirus DNA to cervical-cancer screening. N Engl J Med. 2003;348:489–490
  11. Castle PE, Wheeler CM, Solomon D, Schiffman M, Peyton CL. Interlaboratory reliability of Hybrid Capture 2. Am J Clin Pathol. 2004;122:238–245
  12. Sherman ME, Lorincz AT, Scott DR, et al. Baseline cytology, human papillomavirus testing, and risk for cervical neoplasia: a 10-year cohort analysis. J Natl Cancer Inst. 2003;95:46–52
  13. Kjaer S, Hogdall E, Frederiksen K, et al. The absolute risk of cervical abnormalities in high-risk human papillomavirus-positive, cytologically normal women over a 10-year period. Cancer Res. 2006;66:10630–10636
  14. Wang SS, Walker JL, Schiffman M, Solomon D. Evaluating the risk of cervical precancer with a combination of cytologic, virologic, and visual methods. Cancer Epidemiol Biomarkers Prev. 2005;14:2665–2668
  15. Walker JL, Wang SS, Schiffman M, Solomon D. Predicting absolute risk of CIN3 during post-colposcopic follow-up: results from the ASCUS-LSIL Triage Study (ALTS). Am J Obstet Gynecol. 2006;195:341–348
  16. Stoler MH, Castle PE, Solomon D, Schiffman M. The expanded use of HPV testing in gynecologic practice per ASCCP-guided management requires the use of well-validated assays. Am J Clin Pathol. 2007;127:1–3
  17. Cox JT, Schiffman M, Solomon D. Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy. Am J Obstet Gynecol. 2003;188:1406–1412
  18. Castle PE, Stoler MH, Solomon D, Schiffman M. The relationship of community biopsy-diagnosed cervical intraepithelial neoplasia grade 2 to the quality control pathology-reviewed diagnoses: an ALTS report. Am J Clin Pathol. 2007;127:805–815
  19. Gage JC, Hanson VW, Abbey K, et al. Number of cervical biopsies and sensitivity of colposcopy. Obstet Gynecol. 2006;108:264–272
  20. Brewster WR, Hubbell FA, Largent J, et al. Feasibility of management of high-grade cervical lesions in a single visit: a randomized controlled trial. JAMA. 2005;294:2182–2187
  21. Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet. 2006;367:489–498
  22. Mosher WD, Chandra A, Jones J. Sexual behavior and selected health measures: men and women 15-44 years of age, United States, 2002. Adv Data. 2005;1–55
  23. Parkin DM, Bray F. The burden of HPV-related cancers. Chapter 2 Vaccine. 2006;24(Suppl 3):S11–S25S11-25
  24. Kurman RJ, Henson DE, Herbst AL, Noller KL, Schiffman MH. Interim guidelines for management of abnormal cervical cytology (The 1992 National Cancer Institute Workshop). JAMA. 1994;271:1866–1869
  25. Solomon D, Breen N, McNeel T. Cervical cancer screening rates in the United States and the potential impact of implementation of screening guidelines. CA Cancer J Clin. 2007;57:105–111
  26. Gail MH, Brinton LA, Byar DP, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989;81:1879–1886
  27. Castle PE, Solomon D, Schiffman M, Wheeler CM. Human papillomavirus type 16 infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities. J Natl Cancer Inst. 2005;20:1066–107197
  28. Arbyn M, Paraskevaidis E, Martin-Hirsch P, Prendiville W, Dillner J. Clinical utility of HPV-DNA detection: triage of minor cervical lesions, follow-up of women treated for high-grade CIN: an update of pooled evidence. Gynecol Oncol. 2005;99:S7–S11
  29. Solomon D, Schiffman M, Tarone R. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst. 2001;93:293–299
  30. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356:1915–1927

 Cite this article as: Castle PE, Sideri M, Jeronimo J, et al. Risk assessment to guide the prevention of cervical cancer. Am J Obstet Gynecol 2007;197:356.e1-356.e6.This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. The financial activities of P.E.C., J.J., D.S., and M.S. are monitored by the National Cancer Institute Ethics Office.

PII: S0002-9378(07)00932-5

doi:10.1016/j.ajog.2007.07.049

American Journal of Obstetrics & Gynecology
Volume 197, Issue 4 , Pages 356.e1-356.e6, October 2007

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