By Kathleen M. Murphy, Ph.D.
Background: Infection with Human Papilloma Virus (HPV) is the leading risk factor for the development of cervical cancer. Although greater than 100 types of HPV exist, only approximately 14 are considered “high risk” (HPV-HR) because they are associated with the development of cervical cancer. Of the high-risk types, two, HPV 16 and 18, represent the greatest risk, together accounting for approximately 70% of cervical cancers. There are currently two types of FDA-approved HPV tests available; testing for all high-risk types (HPV-HR), and genotyping specifically for HPV 16 and 18 (HPV 16/18).
Clinical Utility: While it is widely recognized HPV testing adds value to cervical screening, the use and interpretation of the test can be challenging. This is primarily because the prevalence of HPV is significant (up to 30% in some populations). However, it is only women who do not clear the infection, and the infection remains persistent, who are at risk of cervical disease. For this reason, the value of HPV testing is greatest in distinct clinical settings.
The FDA has approved HPV testing, and the American Society for Colposcopy and Cervical Pathology (ASCCP) Consensus Guidelines recommend the use of HPV-HR testing for two clinical scenarios (See below). The ASCCP guidelines specifically recommend testing for high-risk types of HPV only (not low-risk types).
Management of women with ASC-US cervical cytology
HPV-HR testing in women with ASC-US cervical cytology has a very high negative predictive value. This means that a negative test result strongly indicates that significant cervical disease (CIN2/3) is not present, and therefore colposcopy is not indicated. The ASCCP guidelines do not recommend colposcopy in the setting of ASC-US cytology and negative HPV results. By implementing HPV-HR testing into the management of women with ASC-US cytology, unnecessary colposcopy procedures can be avoided.
The FDA has cleared the use of HPV 16/18 genotyping in patients with ASC-US cervical cytology results. However, because a negative HPV 16/18 test result is not intended to prevent women from proceeding to colposcopy, the ASCCP Consensus Guidelines do not currently recommend the use of HPV 16/18 genotyping for women with ASCUS cytology.
Screening in women = 30 years old in conjunction with Pap smear testing.
HPV testing in women = 30 with negative/normal cytology has better sensitivity for the detection of cervical disease than Pap testing alone. This means that HPV testing identifies women who, although they have a negative/normal Pap result, may have an increased risk of cervical disease. The ASCCP guidelines recommend that women = 30 with negative/normal cytology who are HPV-HR positive be re-screened at 1 year. Women over 30 with negative/normal cytology and a negative HPV test result have a very low risk of cervical disease and do not require re-screening for 3 years.
The FDA has cleared, and the ASCCP guidelines recommend, the use of HPV 16/18 genotyping in patients with negative/normal cervical cytology who are HPV-HR positive. If the HPV 16/18 genotyping test is positive, the ASCCP guidelines recommend colposcopy, despite the negative cytology. If the HPV 16/18 is negative, re-screening in 1 year is recommended.
At ProPath, we perform HPV-HR testing and HPV 16/18 genotyping using the FDA-approved Cervista™ HPV HR and Cervista™
HPV 16/18 tests. The Cervista™ HPV 16/18 test is the only HPV genotyping test currently FDA-approved. In our experience, and according to scientific literature, the Cervista™ HPV HR has several advantages which include:
• Reduced false positive test results
• Fewer samples rejected due to insufficient specimen volume
• Confirmation of specimen adequacy by the use of an internal control
ProPath offers a full range of HPV testing options which allows our clients to customize testing to best fit their practice needs (Please see our updated requisition form).
1. 2006 Consensus Guidelines for the Management of Women with Cervical Cytology Abnormalities. American Society for Colposcopy and Cervical Pathology. Copyright 2006, 2007
2. Day, SP et al. J Clin Virol. 2009 Jul;45 Suppl 1:S63-72.
3. Cervista™ HPV HR Product Insert. 2009 Third Wave Technologies, Inc.