The first stand-alone HPV screening tool, the cobas HPV Test, was approved by the FDA in 2014 to screen for primary cervical cancer in women over the age of 25 years. In 2011, the cobas HPV test was first approved to work in conjunction with a Pap test. Currently, co-testing with a Pap and an HPV test is recommended for women over the age of 30, but the approval of a stand-alone cobas HPV test has the potential to change this practice. A recent cohort study looked at the specificity of the cobas HPV test as a stand-alone screening test for high-grade cervical lesions.
"In women who are older than 30, we are obtaining both a Pap and an HPV test in order to detect disease. And I think you just can't do any better than that right now."
- Juan Felix, MD
The cobas test is used to identify the presence of HPV 16 and HPV 18, the two types of HPV that are responsible for about 70% of cervical cancer cases, as well as 12 other types of HPV. The test is done using cervical cells taken during a scrape of the cervix. The DNA isolated from those cells is tested for the presence of any HPV DNA, specifically the L1 and L2 genes. If HPV 16 or HPV 18 is present, a follow-up colposcopy is recommended. If another HPV type is found, a Pap test is recommended. If the test comes back negative for any HPV type, no further screening is needed, but the test should be repeated in 3 years.
The effectiveness of the cobas HPV test was put under the microscope during a cohort study at Houston Methodist Hospital. Of the 90,400 Pap tests done at Houston Methodist Hospital between March 2013 and February 2014, 33,875 were included in the study. There were 4,022 patients whose cobas HPV test results returned as positive, and of those, 50.8% also had abnormal cytology. Of the 29,495 patients found to be HPV-negative in the initial cobas test, 10.2% also had abnormal cytology confirmed by biopsy. Researchers found that a total of 59.7% of women who had biopsies that showed abnormal cytology returned a negative result on the cobas HPV test.
The authors of the study concluded that the rates of false-negatives in patients with high-grade cervical lesions screened with the cobas HPV test were "unacceptably high." They further express concern that false-negative results could provide a false sense of confidence for patients and physicians. Believing they are clear of HPV after receiving a negative result on primary screening, women and their physicians may not seek any further tests. The ultimate result could be a delay in diagnosis of and treatment for cervical lesions.
The results of this study may seem alarming, but as Juan Felix, MD, professor of clinical pathology and obstetrics and gynecology and chief of gynecologic pathology at the University of Southern California University and Norris Hospitals pointed out in a phone interview, "We have known from past experiences that the HPV test is not perfect." Dr Felix goes on to say, "The one thing that is incontrovertible and has been present in every single study is that if you use the Pap and an HPV test, your sensitivity will be superior than if you use either HPV or Pap alone."
If the stand-alone HPV test is known for being less specific than co-testing, perhaps the driver behind its use is for cost-effectiveness. However, Dr Felix says that when compared with the prior screening recommendations of a Pap every year, co-testing with Pap and HPV every 3 years has "already achieved a level of cost-efficacy that's outstanding, I don't see a reason to sacrifice, currently, sensitivity, to make it even more cost-effective."
The American Cancer Society has not changed their screening recommendations with the availability of this test, but the data is under review. For women between the ages of 30 and 65, current recommendations are either Pap alone every 3 years, or co-testing with HPV and Pap every 5 years. A Pap test is recommended every 3 years, with follow-up and HPV test in the case of an abnormal result, for women between the ages of 21 and 29.
"In women who are older than 30, we are obtaining both a Pap and an HPV test in order to detect disease. And I think you just can't do any better than that right now," Dr. Felix said.
Zhou HS, Mody R, Luna E, et al. The Sensitivity of the Cobas HPV Test in Detecting Biopsy-confirmed CIN2/3 Cervical Lesions: Analysis of 33,857 Cases with Cytology and HPV Co-testing. J Amer Soc of Cytopath. 2014;3(5):S3.