• Assess risk of progression to high-grade lesions and cervical cancer in women with LSIL

• Refine cervical cancer risk assessment when Pap test results are ambiguous (ie, ASC-H)

Cervical cancer is an important disease in women, with more than 12,000 new cases and over 4,000 deaths projected in 2012.¹ 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.² Detection of these lesions and subsequent treatment can prevent progression in most cases.³ Thus, current guidelines recommend routine Pap testing starting at age 21. High-risk HPV testing is also recommended in select populations.^2,4 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.⁵

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. One such test is the Cervical Cancer, TERC, FISH test, which detects amplification of the human telomerase RNA component (TERC) gene and/or polysomy of chromosome 3. TERC gene amplification and chromosome 3 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.^6-8 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.^8,9 Women with a negative result have a lower risk of progression and theoretically could be followed up more conservatively, thereby reducing unnecessary procedures.^7,8

TERC gene amplification has also been associated with high-grade lesions on biopsy in patients with an ASC-H Pap test result.⁶ Thus, these patients may benefit from immediate colposcopy.

• Women with LSIL or ASC-H Pap results

• Dual-color fluorescence in situ hybridization (FISH)

–   Probe specific for TERC gene at 3q26 locus and a control probe specific for the chromosome 3

pericentric region

–   Cells are scored for amplification (increase in number of copies of TERC relative to control)

–   Cells are scored for polysomy (≥3 probe signals for both TERC and control)

TERC gene not amplified and polysomy not detected.

In women with LSIL cytology, absence of TERC amplification and/or chromosome 3 polysomy suggests a lower likelihood of progression to a high-grade lesion and cancer.

In women with ASC-H cytology, amplification of the TERC gene and/or polysomy of chromosome 3 suggests presence of a high-grade lesion. These women are more likely to benefit from colposcopy.