1. Aetna considers annual cervical cancer screening with conventional or liquid-based Papanicolaou (Pap) smears a medically necessary preventive service. Aetna considers Pap smear screening not medically necessary for women who have undergone complete hysterectomy for benign disease (e.g., no evidence of cervical neoplasia or cancer) or have absent cervix.

   Note: Medically necessary cervical cancer screening is covered under plans that cover routine physical exams, routine gynecological exams and/or routine Pap smears. Please check benefit plan descriptions for details.

2. Diagnostic Pap smears are considered medically necessary when any of the following conditions is met:

   1. Pap smear is accompanied by a diagnosis of a malignancy of the female genital tract (i.e., cervix, ovary, vagina, or uterus); or

   2. There is a description of symptoms or a disease requiring diagnosis by a Pap smear, for example:

      1. Vaginal tumor
      2. Chronic cervicitis

      3. Abnormal vaginal bleeding or discharge; or

   3. Following gynecological surgery for cancer; or
   4. Member has been exposed to diethylstilbesterol (DES); or

   5. Member has any of the following risk factors for cervical cancer:

      1. Immunosuppression
      2. History of cervical, vaginal or vulvar cancer
      3. HIV infection
      4. History of genital HPV infection
      5. Previously abnormal Pap smear
      6. Previous sexually transmitted disease

      7. Multiple sexual partners.

   Diagnostic Pap smears are considered experimental and investigational for all other indications.

3. Aetna considers automated liquid-based thin-layer slide preparation methods (ThinPrep® PapTest^TM, SurePrep^TM Liquid Based Pap Test, AutoCyte PREP System^TM ) medically necessary as an alternative to conventional Pap smears when the criteria for conventional Pap smears are met.

4. Aetna considers automated cervical cancer slide interpretation systems (e.g., FocalPoint Slide Profiler (formerly AutoPap), PAPNET) a medically necessary adjunct to cervical cancer screening.

5. Aetna considers testing for high-risk strains of human papilloma virus (HPV) DNA medically necessary for any of the following indications:

   1. Assessment of women with atypical squamous cells of undetermined significance (ASCUS), using the Hybrid Capture II technique. This is consistent with the National Cancer Institute's interim guidelines for managing abnormal cervical cytology as well as the position of the American Society for Colposcopy and Cervical Pathology (ASCCP) for the management of ASCUS.
   2. Follow up of women with ASCUS who have a previously positive HPV DNA test and negative colopscopy results within the past two years.
   3. Follow up of women with low-grade squamous intraepithelial lesions (LSIL) who have had negative colposcopy results within the past two years.
   4. Follow up of women with atypical squamous cells: cannot exclude high-grade SIL (ASC-H) who have negative colposcopy results within the past two years.
   5. Use in combination with Pap smears for screening women aged 30 years and older. If this combination is used for screening, it is not considered medically necessary to rescreen women who receive negative results on both tests more frequently than every 3 years. This policy is consistent with guidelines from the American College of Obstretricians and Gynecologists (2003).
   6. Assessment of women with atypical glandular cells not otherwise specified (ACG NOS).
   7. Follow up of women with ACG NOS who have had negative colposcopy results within the past two years.

   Note: The medically necessary indications for HPV DNA testing are not affected by pregnancy status.

6. Aetna considers HPV testing experimental and investigational for the following indications:

   1. Use as a primary screening test for cervical cancer in women younger than 30 years of age. According to evidence-based guidelines from the U.S. Preventive Services Task Force (2003), the medical literature does not support HPV testing as a screening test for cervical cancer for younger individuals whose cervical cytology is normal or is unknown.
   2. For selecting candidates for cervical cancer vaccine.The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices does not recommend HPV testing to select persons for cervical cancer vaccine. 
   3. For testing members with definitively positive cervical cytology, other than follow up of women with ASC-H, LSIL or AGC NOS and negative colposcopy.
   4. Testing for low-risk HPV strains.
   5. Testing of men.
   6. Use for indications other than detection of cervical cancer, such as testing for infection following exposure to HPV.

   7. Use for all indications other than those listed in section V above.

7. Aetna considers cervicography or speculoscopy (Pap-Sure) experimental and investigational for the screening or diagnosis of cervical cancer because of a lack of adequate clinical studies related to their use for these indications.

8. Aetna considers video colpography experimental and investigational for cervical cancer screening or diagnosis because of a lack of adequate evidence of its effectiveness for these indications.

9. Aetna considers the Resolve^TM laboratory testing kit (Gynecor^TM, Glen Allen, VA) experimental and investigational for cervical cancer screening or diagnosis because of insufficient evidence of its effectiveness for these indications.

See also CPB 650 - Polymerase Chain Reaction Testing: Selected Indications.

Pap smears consist of cells removed from the cervix, which are specially prepared for microscopic examination. The cells are removed by brushing or scraping the cervix during a pelvic examination and then placing the cells on one or more glass slides. Each slide typically contains hundreds of thousands of cells. All Pap smears should be sent to an accredited laboratory to be stained, examined under a microscope, and interpreted. The test is used as the principal screening test to detect cervical cancer in asymptomatic women. It can detect precancerous changes or cancer of the cervix or vagina. A Pap test will only rarely detect cancer of the ovaries or endometrial cancer. It can also find some infections of the cervix and vagina.

The American Cancer Society, National Cancer Institute, American College of Obstetricians and Gynecologists, American Medical Association, and the American Academy of Family Physicians recommend that all women who are or have been sexually active, or who have reached age 18, should have annual Pap smears. The recommendation allows less frequent Pap testing after 3 or more annual smears have been normal, at the discretion of the physician. For women who have had repeated negative tests, the marginal gain from screening more often than every 3 years decreases sharply. However, because of the difficulty in identifying patients at increased risk for cervical cancer, most physicians will recommend a Pap test be performed at least once a year.

After age 65, there is no clear consensus on the need for Pap smears in women who have had previous adequate screening. The American Academy of Family Physicians recommends that at age 65, screening may be discontinued if there is documented evidence of previously negative smears; however, these recommendations are currently under review. The American College of Physicians (ACP) recommends Pap smears every 3 years for women aged 20-65, and every 2 years for women at high risk. The ACP also recommends screening women aged 66-75 every 3 years if not screened in the 10 years before age 66.

Pap testing need not be performed for women who had a hysterectomy for benign disease; however, women who had a hysterectomy performed in which the cervix was left intact probably still require screening. However, a recent study by Sirovich and Welch (2004) indicated that many US women who have undergone hysterectomy are undergoing Pap smear screening despite the U.S. Preventive Services Task Force's recommendation that Pap smear screening is unnecessary for women who have undergone a complete hysterectomy for benign disease.

Repeat Pap smears may be indicated 3-4 months following local treatment of vaginal infection/inflammation, and 2-3 months following a Pap test suggestive of mild dyskaryosis or if the initial Pap smear results were unsatisfactory due to inadequate sampling.

A standardized method of reporting cytology findings was developed by the National Cancer Institute called the "Bethesda System".  In the Bethesda System, atypical squamous cells fall into two categories: atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells: cannot exclude HSIL (ASC-H). Cervical cancer precursors fall into two categories: low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Low-grade squamous intraepithelial lesions include CIN 1 (mild dysplasia) and the changes of HPV, termed koilocytotic atypia. High-grade squamous intraepithelial lesions include CIN 2 and CIN 3 (moderate dysplasia, severe dysplasia, and carcinoma in situ ). Other classification systems in use include the Dysplasia/CIN System and the Papanicolaou System.

Currently there are no formal guidelines for anal Pap smear screening. The most recent recommendations from the Centers for Disease Control and Prevention (Workowski & Berman, 2006) state: "Routine testing for anal cytologic abnormalities or anal HPV infection is not recommended until more data are available on the reliability of screening methods, the safety of and response to treatment, and programmatic considerations."

Automated Liquid-Based Thin-Layer Slide Preparation (ThinPrep, SurePath, AutoCyte PREP)

To decrease the number of false-negative Pap smears, new technologies for preparing the Pap smear have been approved by the U.S. Food and Drug Administration (FDA).

The ThinPrep® PapTest^TM  (Cytyc Corp., Marlborough, MA), and SurePath (TriPath Imaging Inc., Burlington, NC) are automated liquid-based thin layer slide preparation techniques. With the ThinPrep System, a conventional Pap smear is not performed. Using a spatula and a brush or a cervical broom, the cervical area is sampled and the devices are rinsed in a fixative solution. The slide is then automatically made in the laboratory, which decreases the possibility of air-drying artifacts. It is then stained and read by a technician or a cytopathologist. SurePath (formerly known as AutoCyte PREP) is another liquid-based thin-layer sample preparation system that uses centrifugation to separate cells from obscuring material, and automatically prepares and stains cytology slides.

An assessment of liquid-based cervical cytology systems by the Institute for Clinical Systems Improvement (2003) concluded that liquid-based cytology is an acceptable alternative to conventional Pap testing for cervical cancer screening. The ICSI technoloogy assessment made the following findings:

• For the detection of pre-invasive cervical lesions, liquid-based cytology is comparable to conventional Pap; there is no evidence of a change in the rate of cancer detection when liquid-based samples are analyzed.
• For minor grade lesions, there is evidence of a higher detection rate with liquid-based cytology. As a result, liquid-based cytology acts to normalize the rate of detection of atypical squamous cells of undetermined significance (ASCUS) so that pathologists can reach the 3%-5% ASCUS rate expected (Bethesda criteria). More accurate detection of ASCUS helps to better identify patients who need further testing. Interobserver validity is higher with LBC.
• Of 11 studies cited in the ICSI technology assessment that presented test results as either satisfactory, satisfactory but limited by, or unsatisfactory, 8 found a higher rate of satisfactory samples with liquid-based cytology. Between 75.6% and 97.7% of liquid-based cytology preparations were satisfactory compared with 60.5% to 97.5% with conventional Pap preparations.
• The ICSI report cited the results of a metaanalysis of 15 studies that reported a sensitivity of 80% for liquid-based cytology and 72% for conventional Pap testing predominantly for the detection of low grade squamous intraepithelial lesions or more severe (LSIL+) by histology and/or independent pathology review of slides with a Pap test result of LSIL+. Specificity did not differ between conventional and liquid-based cytology preparations.

A technology assessment by the Canadian Coordinating Office for Health Technology Assessment found that "[e]vidence (based primarily on results from split-sample trials) suggests that compared with Pap smears, the use of [liquid-based cytology] reduces the proportion of unsatisfactory specimens and generates fewer false negatives for ordinary populations, but not for high-risk populations" (Noorani, et al., 2003).

In its updated guidelines on cervical cancer screening, the American Cancer Society has stated that liquid-based thin-layer Pap smears are an acceptable alternative to conventional Pap smears (Saslow, et al., 2002). "As an alternative to conventional cervical cytology smears, cervical screening may be performed every two years using liquid-based cytology; at or after age 30, women who have had three consecutive, technically satisfactory normal/negative cytology results may be screened every two to three years (unless they have a history of in utero DES exposure, are HIV+, or are immunocompromised)."

An assessment by the Danish Centre for Evaluation and Health Technology Assessment (DACEHTA, 2005) concluded that "no scientific basis has been found to suggest any difference in clinical or health economic effect between liquid based cytology (LBC) and conventional Pap smear (CPS)." The report noted that "[i] the objective is to improve the clinical or health economic effectiveness, the report demonstrates that an increased coverage rate and an expansion of the age interval included in screening programmes for cancer of the uterine cervix from 59 to 69 years of age would be the more efficient strategy."

Automated System (FocalPoint, PAPNET)

Automated slide analysis devices (e.g., PapNet (Neuromedical Systems Inc.), FocalPoint (formerly AutoPap) (TriPath Technologies, Inc., AutoCyte SCREEN (AutoCyte, Inc.)) are designed to partially automate screening of Pap smears. The primary focus of current research is on use of image analysis as a primary screening device, where Pap smear slides are translated into digitalized images for automated image analysis. Slides that are identified by automated image analysis as possibly abnormal are passed on for manual interpretation. Slides that are identified by automated image analysis as very unlikely to contain abnormal cells may not be examined manually, or a random sample may be spot checked manually. Automated slide analysis devices may also be used to rescreen slides that are reported as negative or inadequate.

Although it is not known whether programs employing automated slide analysis are more effective than manual screening in detecting more cervical cancers, automated slide analysis devices have become standard of care. An Agency for Healthcare Research and Quality technology assessment of cervical cancer screening techniques (McCrory, et al., 1999) concluded that there is substantial uncertainty about the estimates of sensitivity and specificity of cervical cancer screening using automated slide analysis devices compared with conventional manual screening, which in turn results in substantial uncertainty about the estimates of the effectiveness and cost-effectiveness of these techniques. "Although it is clear that both thin-layer cytology and computerized rescreening technologies provide an improvement in effectiveness at higher cost, the imprecision in estimates of effectiveness makes drawing conclusions about the relative cost-effectiveness of thin-layer cytology and computerized rescreening technologies problematic."

A technology assessment for the Minnesota Health Technology Advisory Committee (1999) concluded: "Studies of these methods demonstrate that computer-assisted cervical cancer screening and rescreening modestly improves detection of false-negative smears as compared with conventional manual screening. The majority of false-negative smears detected are low-grade squamous intraepithelial lesions (LGSIL), reactive or reparative changes, or atypical squamous cells of undetermined significance (ASCUS) rather than the more serious premalignant or malignant lesions. Some studies have shown that computer-assisted Pap smear screening may marginally improve health outcome for some patients. The net health benefits of computer-assisted screening have not been proven. Studies examining the cost-effectiveness of the new technologies indicate that the cost-benefit of computer-assisted rescreening technologies is less favorable than any manual rescreening alternatives."

An assessment of the use of automated slide analysis devices in cervical cancer screening conducted by the Research Triangle Institute Evidence-Based Practice Center for the Agency for Healthcare Research and Quality (Hartmann, et al., 2002) concluded that "[o]verall, the quality of this literature is poor for the purposes of making decisions about choice of screening systems in US populations. No randomized trials or prospective cohort studies relate use of a screening modality over time to outcomes for individual women. The cost-effectiveness of use of new technologies has only been estimated, not measured directly."

More recently, the U.S. Preventive Services Task Force (USPSTF, 2003) reached the following conclusions regarding cervical cancer screening using automated slide analysis devices: "The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of new technologies to screen for cervical cancer. The USPSTF found poor evidence to determine whether new technologies, such as liquid-based cytology, computerized rescreening, and algorithm based screening, are more effective than conventional Pap smear screening in reducing incidence of or mortality from invasive cervical cancer. Evidence to determine both sensitivity and specificity of new screening technologies is limited. As a result, the USPSTF concludes that it cannot determine whether the potential benefits of new screening devices relative to conventional Pap tests are sufficient to justify a possible increase in potential harms or costs."

An assessment for the European Cervical Cancer Screening Network's Guidelines for Quality Assurance in Cervical Cancer Screening (Nieminen, 2003) summarized the current evidence for automated cervical cancer slide analysis devices: "There are several articles published concerning the performance of automation assisted screening. They show generally a better sensitivity with at least same specificity than conventional screening. Most of these articles have been retrospective (quality control) and/or relatively small numbers of smears have been studied. However, randomized, prospective public health trials in primary screening setting have been published very few. The show equal or slightly better performance compared to manual conventional screening …. When implementing the new methods, it is needed to carefully ascertain and evaluate the performance of the method in primary (public health) screening up to the final invasive end points with randomized prospective studies."

An assessment for the National Coordinating Centre for Health Technology Assessment (Willis, et al., 2005) concluded: "As in previous health technology assessments on this subject, the conclusion is that the available evidence on test performance, impact on process and cost-effectiveness is still insufficient to recommend implementation of automated image analysis systems. The priority for action remains further research."

Wain (1997) has commented that "[t]he performance of automated techniques in quality assurance should be assessed against other methods of quality assurance, such as random re-screening of a mandated proportion of smears, directed re-screening of 'high-risk' groups and 'rapid re-screening'."

In its updated guidelines on cervical cancer screening, the American Cancer Society expert review panel (Saslow, et al., 2002) only considered screening technologies with sufficient published clinical data, and excluded cervical cancer screening with automated slide analysis devices from its consideration.

HPV Testing

Human papillomavirus (HPV) has been associated with the development of cervical intraepithelial neoplasia (CIN) and invasive cancer of the cervix.  Recent prospective studies have shown that abnormal Pap smears that are positive for oncogenic HPV strains are much more likely to be associated with abnormal colposcopic findings than abnormal Pap smears that are HPV negative. There is no proven value for testing for additional "low-risk" strains of HPV that have not been associated with substantially elevated cancer risk.

HPV testing has been used as an adjunctive reflex test in women with ASCUS to identify those at highest risk for cervical cancer, who should go on to receive definitive colposcopy. HPV testing of patients with ASCUS can be used to identify patients at highest risk of underlying cervical dysplasia, and minimize the number of unnecessary colposcopic examinations in women who have no disease. Women with ASCUS who have a positive HPV and no lesions on colposcopy should be followed up with repeat Pap testing at 6 and 12 months or with HPV testing at 12 months.  Current guidelines do not recommend reflex testing of women with squamous intraepithelial lesions (HSIL, ASC-H, or LSIL).   However, guidelines from the American Society of Colposcopy and Cervical Cytology (Wright, et al., 2001) recommend that women with LSIL or ASC-H with no lesions on colposcopy should be followed up with repeat Pap testing at 6 and 12 months or with HPV testing at 12 months. Current guidelines do not indicate HPV testing for other persons with definitely abnormal cytology,  For an algorithm summarizing the American Society for Colposcopy and Cervical Cytology guidelines on followup of cervical cytological abnormalities (2002), see: http://www.asccp.org/pdfs/consensus/algorithms.pdf.

HPV testing has also been proposed as a primary screening test to be performed simultaneously with Pap smear screening. Digene Corp. received FDA approval for a test that combines the Pap smear with a genetic exam for 13 oncogenic strains of HPV. Aetna, however, does not cover HPV testing as a screening test for cervical cancer for women less than 30 years of age because the evidence is insufficient to determine whether HPV screening reduces the incidence of or mortality from invasive cervical cancer. Aetna's policy is consistent with updated recommendations of the U.S. Preventive Services Task Force (USPSTF) (2003). The USPSTF concluded that the evidence is insufficient to recommend for or against the routine use of human papillomavirus (HPV) testing as a primary screening test for cervical cancer. The USPSTF found "poor evidence to determine the benefits and potential harms of HPV screening as an adjunct or alternative to regular Pap smear screening."

The American College of Obstetricians and Gynecologists (2003) concluded, based on "limited and inconsistent scientific evidence" that the use of a combination of cervical cytology and HPV DNA screening is appropriate for women aged 30 years and older. According to ACOG (2003), if this combination is used, women who receive negative results on both tests should be rescreened no more frequently than every 3 years. ACOG's recommendation was based on the results of studies that demonstrated that women aged 30 years and older who had both negative cervical cytology test results and negative high-risk type HPV-DNA test results were at extremely low risk of developing CIN 2 or CIN 3 during the next 3-5 years (Sherman, 2003; Schiffman, 2000; Belinson, 2001; Petry, 2003). ACOG guidelines explain that any woman aged 30 years or older who receives negative test results on both cervical cytology screening and HPV DNA testing should be rescreened no more frequently than every 3 years. The ACOG guidelines state that the combined use of these modalities has been shown to increase sensitivity but also decrease specificity and increase cost. However, ACOG estimated that the increase in screening interval will offset the cost of this new screening regimen.

The ACOG guidelines (2003) state that the combination of cytology and HPV DNA screening should be restricted to women aged 30 years and older because transient HPV infections are common in women younger than 30 years, and a positive test result may lead to unnecessary additional evaluation and treatment.

Published studies of cervical cancer screening using a combination of cytology and HPV DNA tests have predominantly employed conventional Pap smears for assessment of cervical cytology. Although there are no studies directly comparing the screening performance of HPV-cytology combination testing using a conventional Pap versus liquid-based cervical cytology, available indirect evidence suggests that there is no clinically significant difference in the screening performance of HPV-cytology combination testing regardless of whether conventional or liquid-based cervical cytology is used (Lörincz and Richart, 2003).

The National Cancer Institute is currently sponsoring a multicenter 5-year clinical trial directed at determining the role of HPV testing in the management of cervical disease. Interim guidelines for the management of abnormal cytologic findings in the cervix were developed at a workshop sponsored by the NCI, which concluded that HPV testing can be used as an adjunctive test to help identify patients at low or high risk of developing CIN and cancer. The American Society of Colposcopy and Cervical Pathology has also issued guidelines for the management of ASCUS which incorporated HPV testing and typing to determine which women with ASCUS should undergo colposcopy.

There are no current guidelines recommending HPV testing of men (CDC, 2006; Workowski & Berman, 2006).  There is no FDA-approved HPV test for men, and there are no studies demonstrating benefit of testing men for HPV infection. Unlike with cervical ASCUS, HPV typing has not been shown to aid in predicting which patients with anal ASCUS are at risk for high-grade AIN (Panther, et al., 2003).

Saqi and colleagues (2006) evaluated the potential role of HPV DNA testing on atypical glandular cells (AGC) cases.  Hybrid Capture 2 (Digene Corp.) testing was performed on 144 cervical/endo-cervical AGC specimens.  A total of 103 of 144 cases had follow-up; 60/103 (58.3 %) were high-risk HPV negative and 43/103 (42.3 %) were high-risk HPV positive.  Of 43 HPV-positive patients, 37 had adenocarcinoma in situ (AIS), ASCUS, or cervical squamous intra-epithelial neoplasia, while only 1 patient without high-risk HPV had a squamous intraepithelial neoplasia.  Furthermore, most high-risk HPV positive AGC cases harbored high-grade squamous intra-epithelial lesion rather than AIS.  The authors concluded that their findings support HPV DNA testing of all AGC specimens to detect cervical, especially squamous, neoplasia.

The American Society for Colposcopy and Cervical Pathology (ASCCP)'s guidelines for the management of women with abnormal cervical cancer screening tests (Wright, et al., 2007) noted that HPV testing is incorporated into the management of AGC after their initial evaluation with colposcopy and endometrial sampling. The recommended postcolposcopy management of women with AGC is to repeat cytologic testing combined with HPV DNA testing at 6 months if they are HPV DNA positive and at 12 months if they are HPV DNA negative. Referral to colposcopy is recommended for women who subsequently test positive for HPV DNA or who are found to have ASCUS or greater on their repeat cytologic tests. If both tests are negative, women can return to routine cytologic testing.

In a randomized study, Mayrand, et al. (2007) examined if testing for DNA of oncogenic HPV is superior to the Pap test for cervical cancer screening.  These investigators compared HPV testing, using an assay approved by the FDA, with conventional Pap testing as a screening method to identify high-grade cervical intraepithelial neoplasia in women aged 30 to 69 years.  Women with abnormal Pap test results or a positive HPV test (at least 1 pg of high-risk HPV DNA per milliliter) underwent colposcopy and biopsy, as did a random sample of women with negative tests.  Sensitivity and specificity estimates were corrected for verification bias.  A total of 10,154 women were randomly assigned to testing.  Both tests were performed on all women in a randomly assigned sequence at the same session.  The sensitivity of HPV testing for cervical intraepithelial neoplasia of grade 2 or 3 was 94.6 % (95 % confidence interval [CI], 84.2 to 100), whereas the sensitivity of Pap testing was 55.4 % (95 % CI, 33.6 to 77.2; p = 0.01).  The specificity was 94.1 % (95 % CI, 93.4 to94.8) for HPV testing and 96.8 % (95 % CI, 96.3 to 97.3; p < 0.001) for Pap testing.  Performance was unaffected by the sequence of the tests.  The sensitivity of both tests used together was 100 %, and the specificity was 92.5 %.  Triage procedures for Pap or HPV testing resulted in fewer referrals for colposcopy than did either test alone but were less sensitive.  No adverse events were reported.  The authors concluded that as compared with Pap testing, HPV testing has greater sensitivity for the detection of cervical intraepithelial neoplasia.

An assessment by the California Technology Assessment Forum (2008) found HPV testing for primary cervical cancer screening did not meet CTAF criteria. The CTAF assessment found that, although incorporation of HPV screening can lead to earlier detection of carcinoma in situ lesions, whether or not this will result in reduced cervical cancer incidence and mortality is not known. The CTAF assessmented noted, in addition, that the two trials that have published long term follow-up used a PCR test that is not currently available in the United States. The CTAF assessment concluded that the evidence is insufficient to recommend for or against the incorporation of HPV testing into cervical cancer screening programs.

Thus, whether HPV testing can replace conventional Pap cytologic testing for cervical cancer screening awaits results from randomized controlled trials and/or recommendations from leading national medical organizations.

Cervicography and Speculoscopy

Cervicography is a procedure in which the cervix is swabbed with an acetic acid solution to identify acetowhite changes in the cervix.  With Cervicography, a photograph of the cervix is taken with a special camera (Cerviscope), and is sent to trained technicians for evaluation (National Testing Laboratories, St. Louis, MO). The technicians determine whether the visual image is most compatible with normal, atypia/metaplasia, intraepithelial neoplasia, or cancer. In contrast, speculoscopy (PapSure) uses a chemiluminescent light to aid naked-eye or minimally magnified visualization of acetowhite changes on the cervix. Both Cervicography and speculoscopy have been used as an adjunct to Pap smear for cervical cancer screening and as a triage method to identify which patients with low grade atypical Pap smears need further evaluation by colposcopy and biopsy. According to practice guidelines from the ASCCP, "there have been insufficient large scale controlled studies related to their use in the triage of LGISL [low grade squamous intraepithelial lesion] to recommend either for or against their use" (Cox, et al., 2000). An International Academy of Cytology (IAC) Task Force (van Niekerk, et al., 1998) concluded that "[t]he role of cervicography, or high resolution photography, as a screening device remains to be defined." The IAC Task Force also noted that "[t]here are, at present, insufficient data for the evaluation of speculoscopy…." The U.S. Preventive Services Task Force (1996) concluded that "[t]here is insufficient evidence to recommend for or against routine screening with cervicography … although recommendations against such screening can be made on other grounds."

Video Colpography

Video colpography (video colposcopy) has been used for imaging the vagina and cervix, and has been proposed for use as a method of cervical cancer screening. In this procedure, a video camera is used to create computerized digital images of the cervix, vaginal fornices and endocervical canal; the system may be interfaced with a computer for image manipulation. The images are evaluated by a video screener for signs of cervical cancer. Etherington, et al. (1997) stated that video colpography has potential advantages as a portable and rapid method of cervical imaging. The investigators stated that video colpography has potential of use in fields of teaching, audit and screening of women with low-grade smear abnormalities. Etherington, et al. (1997) compared video colpography with colposcopy in a pilot study involving 50 women referred for colposcopy. The investigators reported that the video colpography images were satisfactory or good in 47 (94%) cases, and there was agreement between colposcopist and video screener in 86% of cases. The investigators stated that, if the technique had been used in a primary health care setting as a secondary screening method for women with low grade cervical smear abnormalities, 61% would have avoided referral for colposcopy. The investigators concluded that "before the technique can be implemented as part of the screening process, it needs to be evaluated in a larger series …" Other publications have described the technical performance of video colposcopy (see, e.g., Milbourne, et al., 2005) and the use of video colposcopy as a research tool (Brown, et al., 2005), as an educational tool (see, e.g., Walsh, et al., 2004), in forensic investigations (see, e.g., Mears, et al., 2003), and in colposcopy quality assurance protocols (see, e.g., Ferris, et al., 2004). Regarding use of video colposcopy in quality assurance, Ferris, et al. concluded that "[c]olposcopy quality control by review of digitized colposcopic images in clinical trials warrants further evaluation if the accuracy can be improved."

Resolve^TM 

Colposcopy is a diagnostic procedure in which a colposcope is used to provide an illuminated, magnified view of the cervix, vagina, and vulva to detect malignant and pre-malignant epithelium.  Malignant and premalignant epithelium have specific macroscopic characteristics relating to contour, color, and vascular pattern that can be identified by the colposcopist for directed biopsy.  Colposcopy is the "gold standard" diagnostic tool in the United States for diagnosing cervical dysplasia following abnormal cytology.

The Resolve laboratory testing kit (Gynecor, Glen Allen, VA) is a new colposcopic method that obtains endocervical samples using cytobrushes.  The kit contains 2 cytobrushes and 2 vials of fixative.  The 1st cytobrush is used to clear mucus from the cervix and the 2nd cytobrush is used to abrade cells from the endocervix.  The fixative enables both cytology and histology to be run on both vials.  HPV is also tested from the same specimen.  If HPV is detected, genotyping by PCR is also reported.

There is insufficient evidence of the effectiveness of the Resolve laboratory testing kit for cervical cancer screening or diagnosis.  How this method compares with conventional colposcopy and cytology using quantified values of sensitivity and specificity awaits results from randomized controlled trials and/or recommendations from leading national medical organizations.