Quest Diagnostics last month launched a molecular diagnostic for women who have received unclear reports about their risk of cervical cancer after being tested on standard Pap smears or HPV tests.
The company plans to market the Cervical Cancer TERC test to physicians as a tool that they can use in conjunction with Pap smears and HPV tests to gain more insights into a woman's risk of cervical cancer. The test analyzes the human telomerase RNA component, or TERC, gene marker, for which Quest holds a non-exclusive license from the National Institutes of Health. The test operates on a fluorescence in situ hybridization-based platform and analyzes residual samples from Pap smears.
"The TERC test acts like a ‘second opinion’ when results from conventional screening are unclear," Daniel Jones, medical director of cancer diagnostics services at Quest, told PGx Reporter over e-mail.
A Pap, short for Papanicolaou, gauges a woman's risk of cervical cancer by analyzing changes in cervical cells. A human papillomavirus test detects the sexually transmitted disease and can also identify viral types that place women at high risk for cervical cancer. The TERC test, meanwhile, detects whether a woman carries extra copies of the chromosome arm 3q and harbors amplified TERC genes, which researchers from the NIH and elsewhere have shown in clinical trials to be associated with abnormal cellular changes in the cervix that progress to cancer.
In a study published in the American Journal of Pathology in 2005, researchers led by Kerstin Heselmeyer-Haddad of the National Cancer Institute analyzed 59 previously stained Pap smears with a FISH probe, and reported that patients who had mild-to-moderate growth of abnormal squamous cells in the cervix and progressed to a severe state of cervical cancer displayed a 3q gain.
Data from the study "suggest that 3q gain is required for the transition from cervical intraepithelial neoplasia 1/2 [the mild-to-moderate state] to CIN3 [the severe state] and that it predicts progression," Heselmeyer-Haddad et al. reported. "Of note, 3q gain was found in 33 percent of cytologically normal Pap smears from women who were diagnosed with CIN3 or invasive cervical carcinoma after a short latency."
According to the study authors, the sensitivity of the molecular diagnostic in assessing the progression from CIN1/CIN2 to CIN3 was 100 percent. The specificity of predicting regression or which patients would not progress to severe cervical dysplasia or cancer, however, was 70 percent. "We conclude that the detection of 3q gain and amplification of TERC in routinely collected Pap smears can assist in identifying low-grade lesions with a high progression risk and in decreasing false-negative cytological screenings," Heselmeyer-Haddad et al. concluded.
Quest believes that doctors should use the TERC test for women with abnormal test results by Pap and HPV to identify women who are at high risk or low risk for cervical cancer. By doing this, physicians may be able to recommend additional cervical biopsies and monitoring for women at high risk of the disease, while ruling out the need for such procedures for low-risk women.
The company estimates that as many as 1.5 million women in the US receive a Pap test revealing mild cellular abnormalities. This diagnosis and subsequent treatment "is associated with higher patient anxiety, morbidity and cost, although many cases never progress to cancer," Quest said in a statement.
The TERC test is being launched after the US Preventative Services Task Force and several professional societies this year revised cervical cancer screening guidelines. Instead of annual checkups for cervical cancer, the treatment guidelines now recommend that doctors administer Pap smears every three years for women 21 to 65 years old, or a combination of Pap and HVP testing every five years for women 30 to 65 years old.
These revisions are attributable to the reduction in cervical cancer mortality rates since 1940, when the disease was a major cause of death for US women of childbearing age. In 2010, approximately 4,200 women died of cervical cancer out of an estimated 12,200 women diagnosed with the disease.
However, because doctors are now being advised in treatment guidelines to screen women less frequently, Quest believes that it's even more important to employ more accurate tools to identify women at the highest risk for developing cervical cancer. "Guidelines represent the bare minimum of required clinical practice. We believe each clinician should consider the guidelines to gauge appropriate clinical practice, but ultimately use her or his clinical discretion to manage the individual patient," Jones said. "New guidelines recommending less frequent screening mean testing must be highly reliable to reduce the possibility that at-risk women are missed between screens."
Of course if treatment guidelines were to specifically recommend TERC testing in addition to Pap and HPV tests for unclear cases, Quest would have a much easier time getting doctors to adopt this additional procedure in their practices. Following the launch of the TERC test, Quest is planning to educate physicians, payors, and medical groups about the molecular diagnostic. Additionally, "we intend to engage a dialog regarding consideration of inclusion of genomic testing, including TERC, in future guidelines," Jones noted.
According to Quest, the Medicare national limitation amount for the test is $146.