Printer-friendly format

Infection with the human papillomavirus (HPV) accounts for more than 95 percent of all cervical cancer. The American Cancer Society estimates that in the United States this year, about 11,000 women will be diagnosed with cervical cancer and about 3,700 will die — making this the seventh most common cause of cancer in the nation and the second most common cancer in women worldwide.

Although the rates of cervical cancer have fallen dramatically since the introduction of the Pap test in the 1960s, this screening test stills suffers from a lack of sensitivity for the detection of CIN2+ lesions, resulting in a false negative rate of almost 30 percent. As such, the standard of care now includes high-risk HPV DNA testing in combination with cytology for primary cervical cancer screening (1, 2). HPV DNA testing is almost exclusively performed using the Qiagen/Digene hc2 HPV DNA test, as this is the only FDA-approved option currently on the market.

Despite the existence of more than 100 HPV types, only about 15 have been established as oncogenic or “high risk” (3). The Digene hc2 test, which screens for 13 of these, is currently used in clinical practice for the triage of women with equivocal cytology results (ASC-US) and in conjunction with a Pap test for general screening of all women 30 years of age and older (1, 2).

While the clinical utility of high-risk HPV screening is well established, several studies have highlighted the clinical significance of HPV genotyping, or type-specific high-risk HPV testing (4,5). In particular, it has been observed that HPV types 16 and 18, which collectively cause approximately 70 percent of cervical cancers worldwide, are also associated with increased cumulative incidence rates for CIN3+/cervical cancer when compared to other high-risk HPV types. As such, a high-risk HPV screen that is able to distinguish types 16 and 18 from other high-risk types might provide increased clinical utility for early detection of women at greatest risk for the development of CIN3+/cervical cancer.

In a recent study published in the Journal of the National Cancer Institute, Khan et al. (5) noted that an HPV screening that distinguishes HPV types 16 and 18 from other HPV types could focus clinical attention on women at greatest risk of cervical cancer and permit less aggressive management of other women with HPV infections. The authors also added that this new screening algorithm could help reduce the number of women who are referred to colposcopy for a high-risk positive HPV test result and normal cytology. Although women who carry other types of high-risk HPV will still need to be monitored, follow-up could likely be more conservative.

As such, the incremental clinical benefit for the management of women 30 years of age and older in a primary cervical cancer screening program becomes focused on the triage of those women who are cytology negative but high-risk HPV positive. Under current guidelines, follow-up with repeat cytology and high-risk HPV testing is recommended at six to 12 months (with 12 months now considered the best management approach) with women who are persistently HPV positive being referred to colposcopy at that point in time. Should the FDA approve type-specific HPV 16/18 genotyping assays, it is likely that this testing would be formally adopted into the existing screening algorithm as an adjunctive test to the current high-risk HPV screen. Those women who are found to be 16 and/or 18 positive would be referred immediately to colposcopy, and women who are high-risk HPV positive but 16/18 negative would return at 12 months for follow-up cytology and HPV testing.

References:
1. Wright TC et al. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet. Gynecol. 103:304-309, 2004.
2. Wright TC et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am. J. Obstet. Gynecol. 197:346-355, 2007.
3. Munoz N et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. NEJM 348:518-527, 2003.
4. Schlecht NF et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA 286:3106-3114, 2001.
5. Khan MJ et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. JNCI 97:1072-1079, 2005. http://jnci.oxfordjournals.org/content/vol97/issue14/index.dtl.



Nicholas T. Potter, PhD, FACMG, is the chief scientific officer and director of molecular diagnostics at Molecular Pathology Laboratory Network, Inc., in Maryville. www.mplnet.com



May 2008

Tags:

None

Login and voice your opinion!