We have just discussed how cotesting has greater sensitivity and specificity than using the HPV or Pap tests independently. However, does the type of HPV test affect sensitivity and specificity in cervical cancer screening? We believe so; at PathAdvantage, we recently selected the APTIMA®HPV assay for these important reasons. SPECIFICITY: Most HPV infections are transient, and are rapidly cleared by the host immune system. The majority of HPV testing is DNA based, while the APTIMA HPV assay targets the oncogenic E6/E7 mRNA products of HPV. Consequently, the APTIMA assay is more specific for these clinically meaningful, oncogenic protein producing infections rather than the transient, less significant infections SENSITIVITY: In advanced infections, the virus integrates into the host genome. Integration may cause the loss of large regions of HPV DNA, which are often the target of some HPV tests (such as the L1 region which is the target of the Roche cobas® assay1). Therefore, in advanced disease, only a small amount of integrated DNA may be left in the host cell, meaning that some assays have a false negative HPV rate in cervical cancers. (HPV DNA has been shown to be undetectable in ~10% of women with invasive cancer/carcinoma in-situ.2 3) This integration leads to the mRNA encoding of oncogenes E6 and E7 which are the targets of the APTIMA assay and are retained after infection, while these other assay targets may be lost. Scope_4_chart A recent study4 compared 6 HPV tests in the same population of 6000 women under- going routine cervical cancer screening. In summary, all the tests (with one exception) showed very high sensitivity. However, the APTIMA assay was the most specific of these tests, with approximately 5% fewer false positives than the other sensitive tests. (The NorChip test was actually the most specific of the group, although at significant cost to sensitivity.) It is this retention of sensitivity, with increased specificity, that led us to select the APTIMA assay at PathAdvantage for HPV testing.

BIBLIOGRAPHY 1 Website: https://www.hpv16and18.com/labs/medical-value/ assay-design.html 2 Wheeler et al. Human papillomavirus genotype distributions: implications for vaccination and cancer screening in the United States.J Natl Cancer Inst. 2009 Apr 1;101(7):475-87. 3 Yee et al. Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines.Am J Pathol. 1985 Jun;119(3):361-6. 4 Cuzick et al..Comparing the performance of six human papillomavirus tests in a screening population. Br J Cancer. 2013 Mar 5;108(4):908-13.