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Cervical Cancer: Significance of HPV 16 & 18

December 12, 2010

Approximately a dozen HPV genotypes (including types 16 and 18) are considered to be “high-risk” because they are the most oncogenic, due to their ability to integrate into the host DNA and cause uncontrolled proliferation of the infected cells. Some of the HPV “early” genes, such as E6 and E7, are known to act as oncogenes that promote tumor growth and malignant transformation.  Persistent infection with high-risk viratypes places a woman at increased risk for developing invasive cancer.

An article published in The Journal of the National Cancer Institute, titled “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,” in 2005 demonstrated that HPV 16 and 18 screening may identify women at greatest risk for  cervical cancer (CIN3)1.

The data in the publication was based on the findings of the National Cancer Institute’s study of over 20,000 women in Portland, Oregon, that concluded HPV types 16 and 18 cause 60-70% of cervical cancers among women 30 years of age and older.  The Portland study of 20,810 women covered by the Kaiser Permanente Health Plan occurred from April, 1989, to November, 1990.  These women were followed for the next ten years.  The incidence rate of CIN 3 was 17.2% for women with HPV type 16 and 13.6% for women found to have HPV type 18.

The women in this study had a median age of 34 years and satisfactory baseline cytology.  It was determined that HPV typing for 16 and 18 may identify women at greatest risk for CIN 3 and may permit less aggressive management of women with other oncogenic types of HPV infections.  Separate analysis was performed on 13,000+ of the women in the study who were over 30 years of age to address age-specific screening recommendations.  One of the conclusions was that HPV 16 positivity did appear to confer a higher 10-year risk for CIN 3 and invasive carcinoma than the other risk groups.

The ten year cumulative incidence rate of CIN 3 or cancer was 17% among women who tested positive for HPV 16 at enrollment and 13.6% in HPV 18+/HPV 16- women. In contrast, the cumulative incidence for CIN 3 was only 3% in women who tested positive for high-risk HPV but was negative for HPV 16 or HPV 18 genotypes.

The available scientific data suggests that distinction of HPV 16 and HPV 18 infections from other high-risk oncogenic HPV types would identify patients more likely to progress to CIN 3, which is the immediate precursor to invasive squamous cell carcinoma.  Women with non-HPV 16/18 still need to be followed closely, but their care can be managed in a more conservative manner.

In 2009, ASCCP released an algorithm for using genotyping for HPV 16 and 18 to triage high-risk HPV-positive/cytology-negative women.  This flow chart outlines a follow-up algorithm based on the detection of abnormal cytology, the employment of HPV DNA testing and, specifically, the detection of HPV 16 and 18 genotypes.

InCyte Pathology offers physicians the ability to perform HPV 16 and 18 genotyping from the Pap collection on your patient.  This test needs to be specifically requested as an additional test to reflex HPV testing for ASC-US Pap results or co-testing in patients older than 30 years.

References:

(1) Khan MJ, Castle PE, Lorincz AT, 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. J Natl Cancer Inst. 2005;97:1072–1079.

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