HPV types 16 and 18 cause 60-70% of cervical cancers worldwide, with the remaining high risk HPV types causing essentially all remaining cases. With the need for stratifying HPV-positive (cytology negative) patients, genotyping for HPV types 16 and 18 has been used to try to help identify women at higher risk for cervical cancer (or its precursor, severe dysplasia/CIN 3). In a 10-year study of HPV and cervical disease1, the 10-year incidence rates of CIN 3 or greater were 17.2% for women testing positive for type 16, 13.6% for type 18 and 3% for other high risk HPV types. These differences are certainly notable, and genotyping is currently an acceptable adjunct in both the ASCCP and ACOG cervical cancer screening guidelines. However, consider the following: Given the above statistics, the majority of women with a negative cervical cytology result who test positive for HPV types 16/18, will NOT develop CIN 3+. Conversely, a woman who tests negative for these two high risk HPV types is not protected from cervical cancer. Therefore, the former group may undergo unnecessary follow up (or even eventual excision) with the knowledge that they are carrying a particularly high risk type of HPV, which is troubling for both the patient and the clinician. Additionally, the association of HPV types 16/18 with high grade cervical disease varies across geographic and racial boundaries. An article published in Cancer2 found African-American race, Hispanic ethnicity, and areas of poverty to be associated with a lower incidence of types 16/18 among women with high-grade cervical disease. An additional study3 showed African-American women to be TWO TIMES less likely to harbor HPV 16/18, even with high grade cervical disease. THE BOTTOM LINE: while HPV types 16 and 18 cause the majority of cervical cancers worldwide, positivity for these genotypes does not predict the development of such; nor does negativity for types 16/18 negate the risk for high grade cervical disease.

Image: A normal cell with 2 copies of 3q26 (TERC), one of the most commonly tested for chromosomal abnormalities in cervical disease, which is seen in about 75% of cervical cancers.

BIBLIOGRAPHY 1 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. J Natl Cancer Inst. 2005 Jul 20;97(14):1072-9. 2 Niccolai LM, et al. Individual and geographic disparities in human papillomavirus types 16/18 in high-grade cervical lesions: Associations with race, ethnicity, and poverty. Cancer. 2013 Aug 15;119(16):3052-8. 3 Vidal AC, et al. HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA. Cancer Causes Control. 2014 Aug;25(8):1055-62. Article written by PathAdvantage pathologist Richard Hopley, MD.