Laboratory Section - Cervicography

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

Cervicography consists of the use of a specialized camera to take standardized images of the cervix after application of acetic acid. The device is described as easy to use and does not require experience in colposcopy. The photographs, referred to as "cervigrams," are static photographic images of the cervix similar to those seen during low-level magnification colposcopy. The images are sent to a central laboratory (National Testing Laboratories, the world-wide exclusive licensee of the product) for interpretation by colposcopists who have received specialized training in interpretation of cervigrams. Cervigrams are interpreted as negative, atypical, positive, or defective.

Cervicography has been investigated in three general settings:

• As an alternative to Pap smear screening as a primary screening technique for cervical cancer. This application has been investigated primarily in "resource poor" areas that do not have cytology expertise to interpret Pap smears.
• As an adjunct to routine Pap smear screening to improve the sensitivity of Pap smear screening for cervical cancer. It is estimated that negative cytology reports are issued on 20% or more of all invasive cervical cancers.
• As a triage technique for colposcopy in patients found to have low-grade lesions on Pap smear specimens. The management of low-grade lesions, i.e., atypical squamous cells of uncertain significance (ASCUS), has been the subject of investigation. For example, colposcopy is an option for further work-up of ASCUS lesions, yet at colposcopy only 20% of these patients actually have a high-grade lesion. Furthermore, many low-grade lesions that may prompt colposcopy will spontaneously regress. If cervicography can be used to identify which ASCUS cytology results are most likely to harbor higher grade lesions and thus need colposcopy and biopsy, unnecessary colposcopies in patients with innocuous cytologic abnormalities would decrease. Other triaging strategies include repeat Pap smears or evaluation for human papilloma virus (HPV) infection.

Policy/Criteria

Cervicography is considered investigational.

Position Summary

Cervicography has been the subject of several randomized studies that have investigated its use in various settings, e.g., as a primary screening technique, as an adjunct to Pap smear screening as a primary screening technique, and as a triaging strategy for patients found to have low-grade lesions on Pap smear.

Cervicography as an Alternative to Pap Smear as a Primary Screening Technique

Schneider and colleagues reported on a study comparing cervicography with conventional Pap smear, a conventional Pap smear interpreted with the aid of PapNet (neural network semiautomatic screening device), and a Pap smear prepared from a ThinPrep solution and interpreted conventionally. (2) The study included 8,460 women from Costa Rica, considered a high-risk population for cervical cancer. Patients were referred for colposcopy and potential biopsy if there was an abnormal cytologic result by any one of the three methods above. The sensitivities and specificities of the cytologic testing and cervicography for the most clinically important high-grade lesions compared to a referent diagnosis* are summarized in the following table:

As noted in the above table, the sensitivity of cervicography sharply drops among older, predominantly postmenopausal women. This observation is explained by the cephalad movement of the transformation zone in postmenopausal women. The transformation zone is the site of origin of most cervical cancers, and as it moves cephalad into the cervical canal, it is no longer well visualized with cervicography. The authors concluded that cytologic testing performed better than cervicography for the detection of high-grade intraepithelial lesions, while cervicography was only marginally better in the detection of invasive cervical cancer.

In a study by Cronje and colleagues, 1,286 women were each screened with cytologic examination, cervicography, direct acetic acid test, and speculoscopy. (3) Results were compared to histologic examination to identify a suitable method for screening in a developing country. The authors concluded that none of the methods were individually sufficient for screening. Cervicography results were 48.9% for sensitivity and 87.5% for specificity and were noted to be inadequate for the study purpose due to the low specificity.

One study of interrater reliability using cervigrams was published. (15) This trial used convenience samples of cervigrams obtained for other studies. 72 experienced (4 expert) colposcopists from 5 countries reviewed a sample of 50 cervigrams, representing a spectrum from normal to cancerous, for the presence of lesions and the site of suggested biopsy. Their results were compared to those of the consensus (not histology). Agreement was 70% (65%–75%), which the authors concluded was sufficient for all centers to participate in a trial assessing the best management strategy for biopsy proven CIN1. This study was not intended to assess the screening capacity of cervicography, but does illustrate challenges for the technology.

Cervicography as an Adjunct to Primary Pap Smear Screening

The combined use of Pap smear screening, cervicography and human papilloma virus (HPV) testing has been investigated as a technique to reduce the false negative rate of Pap smear screening alone.

Autier and colleagues performed a randomized study comparing cytology and cervicography. (4) A total of 5,550 women considered at low risk of cervical neoplasia were randomized to one of the screening strategies and rescreened one year later with combined cytology and cervicography. Women positive for either of the two initial screening tests were referred for colposcopy-biopsy. The principal study endpoint was the rate of histopathologically confirmed cervical intraepithelial neoplasia (CIN) lesions. In the cytology only group, 13 of the 2,772 (0.47%) Pap smears were read as abnormal. In contrast, in the combined group, 12 Pap smears were read as abnormal in addition to 101 cervigrams that were read as abnormal. No woman was positive for both Pap smear and cervigram. A total of 13 patients in the cytology alone group were referred to colposcopy, compared to 113 in the combined group. CIN 2-3 (cervical intraepithelial neoplasia grade 2-3) was identified in 4 of the patients in the cytology alone group compared to 6 in the combined group. Therefore, the majority of the patients with abnormal cervigrams were either found to have no lesion or CIN 1 on subsequent colposcopy. CIN 1 lesions are generally thought to be transient in nature and require no specific treatment, but may be followed with repeat Pap smears. While the addition of cervicography to cytology improved the detection of CIN 1 lesions, it did so at a cost of decreased specificity. In addition, detection of CIN 2 and 3 lesions represents the most clinically significant target of screening.

Costa and colleagues reported on the results of 992 patients undergoing routine Pap smears who underwent simultaneous cervicography and HPV testing. (5) All patients also underwent colposcopy as the reference tool. The combination of Pap testing with cervicography resulted in an increase in sensitivity but with a decrease in specificity. The positive predictive value of combined Pap and cervicography (43%) was similar to that of Pap smear alone (45%).

Cervicography as a Triaging Strategy in Women with ASCUS or LSIL on Pap Smears

The ASCUS/LSIL Triage Study (ALTS) was a multicenter, randomized trial that compared three different management strategies for 3,488 women with either ASCUS or LSIL (low-grade squamous intraepithelial lesion) on an initial Pap smear. (6) The strategies included:

1. Immediate colposcopy (considered the reference standard)
2. Triage to colposcopy based on the results of HPV testing
3. Triage based on cytology results alone

The main study endpoint was detection of CIN 3, since there is a general consensus that this lesion is at high risk of progressing to invasive cancer and requires definitive treatment. All patients also underwent cervicography as a "fail safe" mechanism in the noncolposcopy groups to prevent a missed cancer diagnosis. The cervicography results were then interpreted separately as a triaging technique for mildly abnormal cervical cytology results by comparing the results of cervicography with the histologic results of those patients who underwent colposcopy. (7) Cervigrams were categorized as defective, negative, atypical, and positive. Positive cervigrams were further subdivided into additional categories: positive, LSIL, HSIL (high-grade intraepithelial lesion), or cancer. If one considered an atypical cervigram as an indication for referral to colposcopy, the sensitivity of cervicography to detect CIN 3 lesion (high-grade lesion requiring treatment) was 79.3% and would have required the referral of 41.8% of women for colposcopic examination. When increasing the threshold for colposcopic referral to cervigrams interpreted as positive for LSIL, the sensitivity of detected CIN 3 dipped to 65.8%, requiring referral of 26.5% of women for colposcopic exam. In the ALTS trial, cytology and HPV testing were explored as triaging options. The following comparative results were reported:

The authors concluded by stating that cost utility analyses will determine whether and when cervicography, compared with other clinical options, is useful in the management of mildly abnormal cervical cytology results.

In another study, Ferris and colleagues compared cervicography to on-site colposcopy and telecolposcopy in 264 women. (8) The authors found no statistically significant difference in rates of agreement or sensitivity and specificity for each of the screening methods when CIN 1 cases were considered. However, when evaluating CIN 2 and 3 cases, on-site colposcopy out-performed cervicography in rate of agreement and sensitivity as seen in the table below:

The authors concluded that telecolposcopy detected more cervical neoplasia than cervicography.

In a 2004 study, Howard and colleagues compared the diagnostic yield of cervicography and HPV testing among 304 women with ASCUS lesions detected on Pap smears.  (9) The adjunctive tests were compared to the gold standard of colposcopy. The authors concluded that while both adjunctive tests increased the sensitivity of cytology, there was insufficient power to determine whether observed sensitivities were statistically significantly higher than the expected, given that the adjunctive tests could improve the sensitivity by chance alone.

More recent studies continue to evaluate the potential impact of combining cervicography with other tests as a risk-stratification or triage technique. For example, Wang and colleagues reported that combining results of liquid-based cytology, HPV testing, and cervicography could help to determine the risk of subsequent development of cervical precancers. (10) Before this could be used in practice, replication/validation of these findings would be needed.

One study of interrater reliability using cervigrams was published. (16) This trial used convenience samples of cervigrams obtained for other studies. This specific study used 919 cervigrams from the ASCUS-LSIL Triage Study (all subjects referred to the study had either ASCUS or LSIL). Each cervigram was evaluated by 2 expert colposcopists for lesion severity and the number of lesions. The evaluators had complete agreement in 56.8% of cases, disagreement between high- and low-grade lesions in 37.8%, and absolute disagreement in 5.3%. HPV status and age were predictive of agreement. The authors concluded that caution is needed when using static images, even of high quality, for teaching and testing of colposcopists. This study was not intended to assess the screening capacity of cervicography, but does illustrate challenges for the technology.

Guidelines

In 2001, the American Society for Colposcopy and Cervical Pathology (ASCCP) published guidelines for the management of women with cervical abnormalities, in part based on the results of the ALTS study. (11, 12) These guidelines do not recommend cervicography as a triaging strategy.

The 2006 update of the consensus guidelines for the management of cervical abnormalities by the American Society for Colposcopy and Cervical Pathology do not mention cervicography or cervigrams.(17)

The U.S. Preventive Services Task Force (USPSTF) specifically does not recommend cervicography as part of a cervical cancer screening program. (13) The Task Force states that the sensitivity of cervicography is similar to Pap smears, but that both the specificity and positive predictive value are considerably lower than Pap smears. The positive predictive value is only about 1%-26% and up to 10%-15% of cervigrams are unsatisfactory in quality. The Task Force concludes, "There is insufficient evidence to recommend for or against routine screening with cervicography." This recommendation was issued in 1996.

According to the 2003 update to the USPSTF guideline, no current screening guidelines specifically recommend using newer Pap test technologies in favor of conventional Pap tests. (14)

Summary

In summary, cervicography alone has an inferior sensitivity compared to cytology, and therefore is not recommended in settings where adequate cytology services are available. More recent studies continue to evaluate the potential role of cervicography in settings where adequate cytology services are not available.  As an adjunct to Pap smear screening, cervicography may increase the sensitivity for detecting cervical abnormalities but will decrease the specificity, potentially resulting in increased referrals for colposcopy. As a triaging strategy for patients with mildly abnormal cytology results, cervicography is a promising technique that appears to be similar in terms of positive and negative predictive values compared to other options, including repeat cytology or HPV testing. However, if the original Pap smear was collected in a liquid medium, subsequent HPV testing in patients whose cytology was mildly abnormal could be done on the same sample. Therefore, these patients do not need to return for a repeat office visit. Both repeat Pap smear and cervicography would require an additional office visit. At the present time, there are no clinical guidelines from the American College of Obstetricians and Gynecologists, U.S. Preventive Services Task Force or related organizations that recommend the use of cervicography in any of the above clinical situations.

A multispectral digital colposcope, a modified colposcope with a video camera adapter and automated digital image analysis, is in development, and a report of the performance of this technology in a pilot study of 29 patients was identified. (18) Sensitivity was reported at 79% and specificity was 88%. Much larger study populations will be necessary to evaluate the test characteristics of this emerging technology.

References

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 2.04.04
2. Schneider DL, Herrero R, Bratti C et al. Cervicography screening for cervical cancer among 8460 women in a high-risk population. Am J Obstet Gynecol 1999;180(2 pt 1):290-8
3. Cronje HS, Parham GP, Cooreman BF, et al. A comparison of four screening methods for cervical neoplasia in a developing country. Am J Obstet Gynecol 2003;188(2):395-400
4. Autier P, Coibion M, De Sutter P et al. Cytology alone versus cytology and cervicography for cervical cancer screening: a randomized study. Obstet Gynecol 1999;93(3):353-8
5. Costa S, Sideri M, Syrjanen K et al. Combined Pap smear, cervicography and HPV DNA testing in the detection of cervical intraepithelial neoplasia and cancer. Acta Cytol 2000;44(3):310-8
6. 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(4):293-9
7. Ferris DG, Schiffman M, Litaker MS. Cervicography for triage of women with mildly abnormal cervical cytology results. Am J Obstet Gynecol 2001;185(4):939-43
8. Ferris DG, Litaker MS, Macfee MS et al. Remote diagnosis of cervical neoplasia: 2 types of telecolposcopy compared with cervicography. J Fam Pract 2003;52(4):298-304
9. Howard M, Sellors JW, Lytwyn A et al. Combining human papillomavirus testing or cervicography with cytology to detect cervical neoplasia. Arch Pathol Lab Med 2004; 28:1257-62
10. Wang SS, Walker JL, Schiffman M et al. Evaluating the risk of cervical precancer with a combination of cytologic, virologic, and visual methods. Cancer Epidemiol Biomarkers Prev 2005; 14(11 Pt 1):2665-8
11. Wright TC, Cox JT, Massad LS et al. 2001 Consensus Guidelines for the management of women with cervical cytologic abnormalities. JAMA 2002;287(16):2120-9
12. Wright TC, Cox JT, Massad LS et al. 2001 Consensus Guidelines for the management of women with cervical intraepithelial neoplasia. Am J Obstet Gynecol 2003;189(1):295-304
13. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services. Baltimore: Williams and Wilkins, 1996; pp. 105-117
14. www.ahrq.gov/clinic/3rduspstf/cervcan/cervcanrr.htm  (Verified 07/30/08)
15. Elit L, Julian JA, Sellors JW et al. Colposcopists' agreement on cervical biopsy site. Clin Exp Obstet Gynecol 2007; 34(2):88-90
16. Jeronimo J, Massad LS, Schiffman M. Visual appearance of the uterine cervix: correlation with human papillomavirus detection and type. Am J Obstet Gynecol 2007; 197(1):47.e1-8
17. Wright TC, 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(4):346-55
18. Young Park S, Follen M, Milbourne A et al. Automated image analysis of digital colposcopy for the detection of cervical neoplasia. J Biomed Opt 2008; 13(1):014029

Cross References

None

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