Clinical Services

Cervical BioStrat® Assay

Cervical Cancer - Background

Cervical cancer is the second most common cancer among women in developing countries and the seventh most common cancer among women in developed countries.1 In the United States in 2012, it is estimated that 12,170 women will be diagnosed with cervical cancer and 4,220 will die from this disease.2

Progression to cervical cancer begins with the infection of cervical cells by high-risk human papillomavirus (HPV). Although HPV infection usually resolves spontaneously, persistent infection may cause transformation to precancerous lesions that can be detected using cytology (Pap) testing or biopsy.3 The biological pathway to cervical carcinoma is generally accepted to be a multistep progression as follows: 1) normal epithelium, 2) low-grade squamous intraepithelial lesions (LSIL), 3) high-grade squamous intraepithelial lesions (HSIL), 4) carcinoma in situ (CIS) and 5) malignancy. Detection of these lesions and subsequent treatment can prevent progression in most cases.4 Thus, current guidelines recommend routine Pap testing starting at age 21. High-risk HPV testing is also recommended in select populations.3,5 Although this strategy is effective at detecting lesions early, it also results in some cases of unnecessary testing and treatment since only 7% to 21% of low-grade lesions progress to high-grade lesions.6 Accordingly, new tests are needed to more accurately predict which precancerous lesions would actually progress to cancer. Tests based on detection of chromosomal changes, which play an important role in progression to cancer, may prove useful.

Introduction to Cervical BioStrat® Assay

The Cervical BioStrat® Assay is designed to detect copy numbers of TERC (3q26.2) and CTNND2 (5p15.2) regions as well as enumeration of Chromosome 7 (CEP7) via fluorescence in situ hybridization (FISH) in liquid-based cervical cytology samples. When hybridized and visualized, these probes provide quantitative information on gene and chromosome copy number alterations in cervical cells that have been linked to cervical cancer. Specifically, the TERC gene amplification and chromosome polysomy have been associated with progression of low-grade lesions to high-grade lesions and cancer, while their absence has been associated with lack of progression and even regression.7-9 Thus, test results may help refine the risk of progression in women with LSIL. Women with a positive result have a higher risk of progressing to high-grade lesions and invasive cancer and are more likely to benefit from colposcopy.9,10 Women with a negative result have a lower risk of progression and theoretically could be followed up more conservatively, thereby reducing unnecessary procedures.8,9 TERC gene amplification has also been associated with high-grade lesions on biopsy in patients with an ASC-H Pap test result.7 Thus, these patients may benefit from immediate colposcopy.

Criteria for Cervical BioStrat® Abnormality

A specimen is considered 'positive' for FISH-associated evidence of severe dysplasia or carcinoma if greater than 1% cells are detected with multiple copies of TERC (3q26) and/or CTNND2 (5p15) gene regions.

Used in conjunction with Pap and HPV testing, the Cervical BioStrat® Assay can assist in identifying which LSIL and ASCUS HPV+ patients may be at risk of progressing to severe dysplasia. This allows the clinician to optimize patient care and healthcare resources.

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Cervical BioStrat® Images

The following examples of patient specimens demonstrate both the clinical utility of the Cervical BioStrat® Assay as well as its simplicity of interpretation.

Cervical Figure 1 Figure 1: Normal result observed in a cervical epithelial cell after hybridization with the TERC (3q26), CTNND2 (5p15) and chromosome 7 (CEP7) FISH probe showing two TERC (orange), two CTNND2 (green) and two chromosome 7 (aqua) signals.
Cervical Figure 2 Figure 2: Abnormal result observed in a cervical epithelial cell after hybridization with the TERC (3q26), CTNND2 (5p15) and chromosome 7 (CEP7) FISH probe showing six TERC (orange), two CTNND2 (green) and two chromosome 7 (aqua) signals.

The Cervical BioStrat® Advantage

Current cervical cancer screening tests results can be ambiguous and fail to provide clear insight into which ASCUS/HPV+ or LSIL patients are truly at risk of progression to cancer. The Cervical BioStrat® Assay can be used as an adjunct to standard cervical cancer screening to help assess the risk of disease progression in women with low-grade lesions and the risk of cervical cancer in women with an ambiguous Pap result.

In women with LSIL cytology, absence of increased copy numbers of TERC (3q26) and CTNND2 (5p15) suggests a lower likelihood of progression to a high-grade lesion and cancer. In women with ASC-H cytology, increased copy numbers of TERC (3q26) and CTNND2 (5p15) suggests presence of a high-grade lesion. These women are more likely to benefit from colposcopy and more intensive follow-up.

Information provided by this test is additive to cytology findings and largely independent of HPV infection status. Test results will have the greatest impact on influencing appropriate follow-up interval or treatment plan when Pap test results are equivocal or when cytology and HPV test results are discordant.


Please contact BioVantra Client Support Center at (866) 301-0960 to arrange for Cervical BioStrat® Assay testing. Our experienced Client Support Team can assist with:

  • Cervical BioStrat® Assay Requisition
  • Sample requirements
  • Logistics and specimen transportation
  • Testing methodology
  • Report delivery, status or interpretation
  • Expert oncology and pathology consultations
  • Requests for BioVantra literature and scientific references

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  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. Mar-Apr 2011;61(2):69-90.
  2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. Jan-Feb 2012;62(1):10-29.
  3. Saslow D, Solomon D, Lawson HW, et al. 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. Apr 2012;137(4):516-542.
  4. McCredie MR, Sharples KJ, Paul C, et al. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. May 2008;9(5):425-434.
  5. Moyer VA, on behalf of the USPSTF. Screening for Cervical Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. Mar 14 2012.
  6. Melnikow J, Nuovo J, Willan AR, Chan BK, Howell LP. Natural history of cervical squamous intraepithelial lesions: a meta-analysis. Obstetrics and gynecology. Oct 1998;92(4 Pt 2):727-735.
  7. Andersson S, Sowjanya P, Wangsa D, et al. Detection of genomic amplification of the human telomerase gene TERC, a potential marker for triage of women with HPV-positive, abnormal Pap smears. Am J Pathol. Nov 2009;175(5):1831-1847.
  8. Jalali GR, Herzog TJ, Dziura B, Walat R, Kilpatrick MW. Amplification of the chromosome 3q26 region shows high negative predictive value for nonmalignant transformation of LSIL cytologic finding. Am J Obstet Gynecol. Jun 2010;202(6):581 e581-585..
  9. Heselmeyer-Haddad K, Janz V, Castle PE, et al. Detection of genomic amplification of the human telomerase gene (TERC) in cytologic specimens as a genetic test for the diagnosis of cervical dysplasia. Am J Pathol. Oct 2003;163(4):1405-1416.
  10. Wright TC, Jr., Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management of women with abnormal cervical screening tests. Journal of lower genital tract disease. Oct 2007;11(4):201-222.

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