Histomorphologic assessment and distribution of high-risk human papillomavirus (HPV) types in cervical high-grade squamous intraepithelial lesions with unusual histomorphologic features.

In rare cases, equivocal histomorphology ('deceiving dysplasia') does not allow immediate diagnosis of cervical high-grade squamous intraepithelial lesion (HSIL). We studied whether these cases are correlated with specific high-risk human papillomavirus (hr HPV) types. During 2011-2017, 39 cases of p16-positive cervical tissue biopsies with unusual ('deceiving') dysplastic histomorphology were identified and matched with the same number of controls (typical HSIL samples). Histomorphological characteristics were reviewed blindly and HPV testing was performed using the clinically validated RealTime test (Abbott) and Anyplex HPV 28 (Seegene). HPV 16 and HPV 31 were the two most frequent HPV types in both groups, although minimum, proportional, hierarchical and any etiological attribution estimates for HPV 16 were significantly lower in the deceiving group (13.2%, 21.3%, 23.7% and 23.7%) than in the control group (32.4%, 48.1%, 48.6% and 48.6%). In addition, the distribution of other hr HPV types differed between the two study groups, with five HPV types (HPV 56, 58, 59, 73 and 82) detected only in the deceiving group. Histomorphologic review of both groups (regardless of HPV type) confirmed significant differences in nuclear atypia, maximum lesion thickness and cellularity, although these were diminished when cross-comparisons between HPV16/18 and non-HPV16/18 cases pooled from both study groups were evaluated. Different attribution estimates for HPV 16, HPV 16/18 and non-16/18 hr HPV types in deceiving and control groups were observed, in particular for HPV 16. However, an unusual (deceiving) histomorphology may also depend on unknown HPV-related molecular changes.