Anticipating the impact of the new screening guidelines on cytology and molecular laboratories
Version of Record online: 27 DEC 2012
Copyright © 2012 American Cancer Society
Volume 121, Issue 5, pages 225–227, May 2013
How to Cite
Booth, C. N. (2013), Anticipating the impact of the new screening guidelines on cytology and molecular laboratories. Cancer Cytopathology, 121: 225–227. doi: 10.1002/cncy.21248
- Issue online: 13 MAY 2013
- Version of Record online: 27 DEC 2012
- Manuscript Revised: 25 SEP 2012
- Manuscript Accepted: 25 SEP 2012
- Manuscript Received: 5 SEP 2012
The recently published American Cancer Society, American Society of Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer, by Saslow et al, will undoubtedly impact cytopathology and molecular laboratories in a variety of ways. These 2012 updates follow the last review and update of the cervical cancer screening guidelines by the American Cancer Society published 10 years prior. We are at a time of transition. Although the 6 working groups and authors took time to evaluate the quantity and quality of available evidence to stand behind these new guidelines, future guidelines will depend on additional high-quality studies to move the screening guidelines forward. This commentary will address the short- and medium-term effects of these screening guidelines on cytology and molecular laboratories in regard to number of specimens, quality issues, information technology, and reporting issues. Finally, several areas of consideration for future research that were discussed at the conclusion of the screening recommendations will be addressed.
The 2012 cervical cancer screening guidelines provide age-specific recommendations for both Papanicolaou (Pap) test cytologic screening and for screening with molecular tests for high-risk human papillomavirus (HPV). In addition, the guidelines address postscreening follow-up (eg, screening intervals for screen negatives and follow-up of screen positives), age of screening cessation, and areas for future consideration. It must be noted that in developing these guidelines, the working groups used detection of cervical intraepithelial neoplasia (CIN) grade 3 (CIN3), the immediate precursor to invasive cervical squamous cell carcinoma, to determine a screening test's sensitivity. Although management guidelines use CIN grade 2 (CIN2) as the entrance point for definitive treatment, the working groups did not use CIN2 to determine a screening test's sensitivity. This is because CIN2 is an equivocal diagnosis that includes both precancerous lesions (CIN3) as well as CIN grade 1 (CIN1), which will regress on its own.
There are several reasons why specimen volume for both cytology and molecular laboratories will likely decrease with guideline implementation in the short and medium term. One reason is due to changes in recommended screening intervals as well as cervical screening cessation at age 65 years following adequate prior negative screening. The guidelines recommend that screening should commence at age 21 years and not prior to that time. Although age to begin screening was not investigated as a part of this process, it was previously recommended within the context of the Practice Improvement in Cervical Screening and Management Symposium on Management of Cervical Abnormalities in Adolescents and Young Women. The recommended screening intervals for women aged 21 to 29 years have been lengthened to once every 3 years for patients with negative Pap test results. Prior recommendations for this age group were a yearly conventional Pap test or a liquid-based Pap test once every 2 years. Of note, the working groups considered studies using either conventional Pap tests or liquid-based Pap tests together, given the published evidence of similar sensitivity and specificity for the detection of CIN2 or worse (CIN2+) diagnoses with either cytologic method.[8, 9] Although reflex testing for high-risk HPV for atypical squamous cells of undetermined significance (ASC-US) Pap test results is recommended in this age group, co-testing for HPV is not recommended before age 30, due to the high prevalence of HPV in this population. Between the ages of 30 and 65 years, it is recommended (preferred) that women be screened with a Pap test and HPV test (“cotesting”) every 5 years or with cytology alone every 3 years. Lengthening the cotest screening interval from 3 to 5 years in the 30- to 65-year age group will result in a volume decrease not only for cytology laboratories that result Pap tests, but also for molecular laboratories that perform screening HPV cotests.
Another change that will contribute to a lower volume for gynecologic cytology laboratories is a recommended change for the management of women who have ASC-US cytology results and negative high-risk HPV tests. The 2012 screening guidelines recommend that these women return to screening per their age-specific guidelines (every 3 years for women aged 21 to 29 years and every 5 years for women aged 30 to 65 years). This is in contrast to the 2006 American Society of Colposcopy and Cervical Pathology consensus guidelines that recommend repeat cytologic testing for this cohort of patients at 12 months. This change will also contribute to an overall decreased volume for gynecologic cytology laboratories.
In regard to laboratory quality, the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) in section 493.1274 state that, “The laboratory must establish and follow written policies and procedures for a program designed to detect errors in the performance of cytologic examinations and the reporting of results. The program must include the following: For each patient with a current HSIL, adenocarcinoma, or other malignant neoplasm, laboratory review of all normal or negative gynecologic specimens received within the previous 5 years, if available in the laboratory (either on-site or in storage). If significant discrepancies are found that will affect current patient care, the laboratory must notify the patient's physician and issue an amended report.” The lengthening of screening intervals to 5 years for co-tested patients aged 30 to 65 years will result in a lack of available prior negative Pap tests in patients with a new Pap test result of a high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma, or other malignant neoplasm for quality assurance review. This is because CLIA '88 requires laboratories to retain cytologic preparations for at least 5 years from the date of examination, after which time they can be discarded. The patients in the 21- to 29-year age group and those in the 30- to 65-year age group who receive only cytologic testing as recommended every 3 years will have prior negative Pap tests available for review within the new system.
Although laboratory information systems (LISs) and reporting issues are not specifically addressed in the 2012 screening guidelines, it is imperative that cytology and molecular LISs are able to interface with one another. Laboratories report the results of cytologic and HPV testing in a variety of ways. Clinicians may be sending their patients' Pap tests and HPV tests to different laboratory facilities, or cytology and molecular laboratories within the same institution may have separate reporting systems. Both laboratories and clinicians need to be able to readily correlate cytologic results with high-risk HPV testing results to determine appropriate patient follow-up, management, and screening intervals for women of all ages. This applies not only to patients 30 years and older who receive screening co-tests, but also to patients of all ages who have ASC-US cytology results with HPV tests that may be either negative or positive. The ability to quickly and easily review and respond to the results of both tests will result in more efficient and appropriate patient care. The outlook for result correlation is optimistic as medical systems within the United States continue to implement electronic medical record systems for their patients. However, laboratories must advocate for LISs to readily interface with one another and to report the results of the 2 tests together whenever possible.
The guidelines recommend that the most important area for future research needs to focus on identifying means to study the population of women who have never been previously screened. These women, as well as those who have had inadequate prior cervical cancer screening (the underscreened), are women who are at significant risk to develop cervical precancer and carcinoma. Women who have never been screened or who have been inadequately screened constitute approximately one-half of diagnosed cervical carcinomas worldwide. Both cervical cancer incidence and mortality would be reduced if concerted efforts were made to improve cytologic and HPV screening access to women who have not been adequately screened. HPV testing of self-collected vaginal samples has shown at least comparable sensitivity to cytologic screening. This self-collection method may allow for greater access to screening and help to reduce cervical cancer incidence and mortality in this population.
A summary of the anticipated changes for gynecologic cytology and molecular laboratories from the 2012 screening guidelines include decreased volume, reduced opportunities for quality review of prior negative Pap tests, and a need for increased coordination between LISs for reporting of results.
The 2012 screening guidelines, following systematic evidence review by 6 working groups, stress increased screening intervals for all ages, in order to reduce the harms related to unnecessary treatment (colposcopy) of equivocal cytologic interpretations and/or transient HPV infections. The guidelines reinforce that screening should not begin until age 21 years and should cease at age 65 years in patients with negative cervical carcinoma histories. Acceptance of the 2012 guidelines and successful implementation of these lengthened screening intervals will require education of medical professionals and patients alike.
No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURE
The author made no disclosures.
- 1American Cancer Society; American Society for Colposcopy and Cervical Pathology; American Society for Clinical Pathology. 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;137:516-542., , , et al;
- 10Medicare, Medicaid and CLIA programs; regulations implementing the Clinical Laboratory Improvement Amendments of 1988 (CLIA)-HCFA. Final rule with comment period. Fed Regist. 1992;57:7002-7186.