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LUMA Cervical Imaging System The evidence consists of two non-peer-reviewed studies that are summarized in the Premarket Approval (PMA) application submitted to the Food and Drug Administration (FDA) by the device manufacturer. Although both of these studies were large, only the smaller of the two studies evaluated the LUMA Cervical Imaging System for its intended use. Both studies involved histopathological analysis of biopsy samples with the assumption that this analysis would detect any neoplasia present in biopsy specimens. (FDA-LUMA Cervical Imaging System; Wright, 2002) FDA's approval was based on data from a multicenter study that tested the LUMA Cervical Imaging System in 193 women (mean age of 28.5 years) who underwent colposcopy, followed by LUMA. Women with abnormal Pap tests underwent biopsy of suspicious lesions seen during colposcopy but did not undergo a LUMA exam until after biopsy of any suspicious lesions seen during colposcopy alone. If no lesions were seen during colposcopy, the women were deemed negative for CIN grade 1 (CIN 2/3+). If a biopsy was taken but CIN 2/3+ was not present, the result was considered a false positive. A total of 41 (21.2%) women were positive for CIN 2/3+ based on colposcopy alone and an additional 9 (4.7%) women were positive for CIN 2/3+ when the LUMA system was used to direct subsequent biopsies.
The PMA application also included data from a second multicenter study that evaluated the diagnostic capabilities of the LUMA system in 2186 women with a mean age of 30.4 years who were randomly assigned to biopsies guided by conventional colposcopy alone (n=1096) or guided by conventional colposcopy with concurrent use of the LUMA system (n=1090). All of these women were referred to colposcopy due to abnormal Pap test results. The detection rate for cervical neoplasia was 21.8% with the LUMA system versus 19.9% for conventional colposcopy alone; however, this difference was not statistically significant. Likewise, there were no statistically significant differences in detection rate with and without the LUMA system for patients who had atypical squamous cells, low-grade squamous intraepithelial lesions, or high-grade squamous intraepithelial lesions. This study also estimated the false-positive rates for detection of cervical neoplasia using both diagnostic strategies. Although the overall false-positive rate was 60.5% with the LUMA system versus 57.4% with conventional colposcopy alone, this difference was not statistically significant. In contrast, a statistically significant increase in false-positive results was associated with use of the LUMA system in women who had atypical squamous cells. Similarly, women who underwent a LUMA scan were more likely to undergo biopsy (1.30 versus 1.03 biopsies per patient on average).
Since this study involved concurrent use of colposcopy and the LUMA system, it did not evaluate this diagnostic system for its intended use.
Results of the available studies of the LUMA Cervical Imaging System are contradictory and fail to provide conclusive evidence that this device increases the detection of cervical neoplasia. The smaller intended use study indicated that after biopsies guided by colposcopy, further biopsies guided by the LUMA system enabled a statistically significant increase in the detection of CIN 2/3+. A statistically significant increase in false-positive results or unnecessary biopsies was also observed. The larger study of the LUMA system did not confirm the results of the smaller study. In addition to their contradictory conclusions, the available studies failed to present evidence that an improved CIN detection rate improves patient outcomes such as survival or freedom from development of cervical cancer.
Huh et al. collected data from 604 women during routine colposcopy examinations at 6 clinical centers using a cervical scanning device and video images from 604 women during routine colposcopy (Huh, 2004). A statistically significant dataset was developed of intrinsic fluorescence and white light-induced cervical tissue spectra that was correlated to expert Cervical Cancer Screening - Commercial Medical Management Guideline histopathologic determination. On the basis of a retrospective analysis of the acquired data, a classification algorithm was developed, validated, and optimized. Algorithm performance demonstrated a sensitivity of approximately 90%. With the use of a multivariate classification algorithm, optical detection is predicted to detect 33% more high-grade cervical intraepithelial neoplasia (2/3+) than colposcopy alone. The authors concluded that full cervix optical interrogation for the detection of highgrade cervical intraepithelial neoplasia is feasible and appears capable of detecting more high-grade cervical intraepithelial neoplasia than colposcopy alone.
Professional Societies American College of Obstetricians and Gynecologists (ACOG): In July 2003, ACOG issued new recommendations regarding cervical cytology screening. In addition to making changes regarding recommendations for screening frequency, ACOG stated that evidence-based data indicate that both liquid-based and conventional methods of cervical cytology are acceptable for screening. The ACOG recommends the same screening interval, regardless of type of test (conventional or liquid-based cytology) used. Furthermore, the ACOG recommends that the use of a combination of cervical cytology and HPV DNA screening is appropriate for women aged 30 years and older. Once women test negative on both tests (HPV and cytology), they should be rescreened with the combined test no more frequently than every 3 years. If only one of the tests is negative, however, more frequent screening will be necessary (ACOG, 2003).
American Society for Colposcopy and Cervical Pathology (ASCCP): In September 2001, the ASCCP hosted a consensus conference to develop evidence-based guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors, using the 2001 Bethesda System for cytological classification. Based on good evidence for efficacy from at least one RCT, the recommended management of women with ASC-US is (1) two repeat cytology tests; (2) immediate colposcopy; (3) or DNA testing for high-risk types of HPV. When liquid-based cytology is used or when cocollection for HPV DNA testing can be done, reflex HPV DNA testing is the preferred approach. The recommended management of women with ASC-H (atypical squamous cells cannot exclude HSIL) obtained using either conventional or liquid-based cervical cytology is referral for colposcopic evaluation. Other recommendations include: (1) women with atypical glandular cells (AGC), as well as those with adenocarcinoma-in-situ (AIS), should be referred for immediate colposcopy with endocervical sampling, with the exception that women with atypical endometrial cells should be evaluated initially with endometrial sampling; (2) colposcopy is the recommended management option for women with LSIL; and (3) colposcopy with endocervical assessment is the recommended management of women with HSIL. All recommendations, with the exception of those for women with ASC-US, are based on good evidence for efficacy from at least one nonrandomized clinical trial, from cohort or case-control analytic studies, from multiple time-series studies, or dramatic results from uncontrolled experiments. (Wright, 2002) U.S. Preventive Services Task Force (USPSTF): The 2003 USPSTF recommendations for cervical cancer screening state that women who are sexually active and have a cervix should begin have routine cervical cancer screening within 3 years of the start of sexual activity or age 21, whichever comes first, with repeat screenings at least every 3 years. For women older than 65 who have had normal Pap smears, the benefits of continued screening may not outweigh the potential harms, such as false-positive test results and invasive procedures. The Task Force also concludes that the yield of detecting vaginal neoplasms is too low to justify continuing screening after a total hysterectomy (AHRQ, 2003).
In addition, the USPSTF found that available data is insufficient to determine whether newer, more expensive forms of Pap tests are better than conventional Pap tests. Although some data suggest new tests like ThinPrep® may detect more highgrade lesions, they may also increase false-positive results. HPV tests are not yet approved for use as primary screening tests for cervical cancer but research is underway to determine whether HPV tests can identify women who need more or less frequent screening with Pap tests. (AHRQ, 2003) American Cancer Society (ACS): The ACS published updated guidelines for cervical cancer screening in November 2002.
These are summarized as follows: (1) screening should begin approximately 3 years after initiation of sexual intercourse, but no later than 21 years of age; (2) screening should be done every year with conventional cervical cytology smears or every 2 years using liquid-based cytology; (3) women 30 years of age or older who have had 3 normal consecutive Pap test results Cervical Cancer Screening - Commercial Medical Management Guideline may be screened every 2 to 3 years; (4) women 70 years of age and older who have had 3 or more normal Pap tests and no abnormal tests in the last 10 years, and women who have had a total hysterectomy, may choose to stop cervical cancer screening. (ACS, 2008a ) Regarding HPV DNA testing, the ACS recommends that testing for HPV can be used as a screening test (along with the Pap test) in women over 30 as well as for women with slightly abnormal Pap test results to see if more testing or treatment might be needed (ACS, 2008b).
National Cancer Institute (NCI): NCI has published their conclusions, based on statistical reviews and study data, that regular screening of appropriate women for cervical cancer with the Pap test reduces mortality from cervical cancer by at least 80% (NCI 2009).
• Screening is effective when started within three years after first vaginal intercourse.
• Screening is not helpful in women who do not have a cervix.
• Continued screening in elderly (e.g., age 60 years or older) women who have had three negative annual Pap tests is of minimal value.
• Regular screening with the Pap test leads to additional diagnostic procedures (e.g., colposcopy) and treatment for lowgrade squamous intraepithelial lesions (LSIL), with uncertain long-term consequences on fertility and pregnancy. These harms are greatest for younger women, who have a higher prevalence of LSIL, lesions that often regress without treatment.
References and Resources Resources Agency for Healthcare Research and Quality (AHRQ) [Web site]. Screening for Cervical Cancer. January 2003. Agency for Healthcare Research and Quality, Rockville, MD.
Available at: http://www.ahrq.gov/clinic/3rduspstf/cervcan/cervcanwh.htm. Accessed March 10, 2009.
American College of Obstetricians and Gynecologists (ACOG) [Web site]. ACOG News Release. Cervical cancer screening:
Testing can start later and occur less often under new ACOG recommendations. July 31, 2003. Available at:
http://www.acog.org/from_home/publications/press_releases/nr07-31-03-1.cfm. Accessed March 10, 2009.
American Cancer Society (ACS). American Cancer Society Guidelines for the Early Detection of Cancer. March 5, 2008a.
Available at: http://www.cancer.org/docroot/PED/content/PED_2_3X_ACS_Cancer_Detection_Guidelines_36.
asp?sitearea=PED. Accessed March 10, 2009.
American Cancer Society (ACS). Overview: Cervical Cancer. Can Cancer of the Cervix be Prevented? April 16, 2008b.
Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_2_2x_Can_Cancer_of_the_Cervix_Be_ Prevented.asp?sitearea=. Accessed March 10, 2009.
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