Cervical parakeratosis/hyperkeratosis as an important cause for false negative results of Pap smear and human papillomavirus test

Abstract

Like any screening method, Pap and HPV tests are subject to false negative results. We investigated the possible relationship between cervical parakeratosis/hyperkeratosis and a false negative result for both Pap and human papillomavirus (HPV) testing. A total of 551 cases with diagnostically adequate cervical biopsies and Pap tests performed concurrently were examined. The vast majority of the cases (75.5%) were of concordance in diagnosis. Among the 135 discordant diagnoses were 98 with low-grade squamous intraepithelial lesion (LSIL) biopsy and negative Pap test and 34 with negative biopsy and LSIL Pap test. With rare exceptions, no significant discordance between concurrent biopsy and Pap test was found in the cases of high-grade squamous intraepithelial lesion (HSIL). Cervical parakeratosis/hyperkeratosis was noted in 87.8% of the LSIL biopsies with concurrent negative Pap tests. An 83.3% HPV-negative rate was also observed in this group. By comparison, parakeratosis/hyperkeratosis was less frequent (62.6%) in the SIL biopsies with concordant concurrent SIL Pap tests and usually seen focally when present. The negative HPV rates for these concordant LSIL and HSIL groups were 12.7% and 0.0%, respectively. Cervical parakeratosis/hyperkeratosis is an important cause for the negative results of Pap and HPV tests in LSIL, and practising gynaecologist and pathologist should be aware of this possible diagnostic dilemma.