Invader HPV Test Reveals a Poorly-Recognized Deceiving Group of Cervical HSIL Associated with HPV Types-not-16/18
S Kitahara, RC Chan, WS Nichols, EG Silva. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Cervical high-grade squamous intraepithelial lesions (HSIL) are easily diagnosed by established histologic criteria. However, we encountered problematic cases that are difficult to diagnose because classic histologic features are absent and metaplastic features are present. p16 & Ki67 stains proved HSIL in these difficult cases. To characterize them, we used the Third Wave Invader (Inv) test (a new human papillomavirus (HPV) screening assay applicable to tissue and amenable to rapid, sensitive & specific detection of 14 high to intermediate risk HPV types) and a panel of immunostains. Results of these difficult cases are compared to classic HSIL cases.
Design: We searched the last 12 months of our pathology files for: HSIL, CINII, CINIII, & p16. To identify cases of difficult HSIL simulating atypical metaplasia, we reviewed all surgical cases of HSIL that required p16 & Ki67 confirmation. Cases of interest were also stained with ProExC. HPV screening & HPV 16/18 typing were performed by the Inv probe sets A5/A6 (HPV 51,56,66), A7 (HPV 18,39,45,59,68) & A9 (HPV 16,31,33,35,52,58) & Inv HPV 16/18 type specific assays.
Results: 10 cases of classic HSIL were easily diagnosed by hypercellularity, significant atypia, mitotic figures & diffuse staining by p16, Ki67 & ProExC. Inv identified HPV16 (A9-positive/HPV16-positive) in 7 of 10 cases; the 3 others were A7-positive/not-HPV18 (1) & A9-positive/not-HPV16 (2). 8 cases of HSIL simulating metaplasia were identified. These showed only mild-moderate cellularity, lacked significant atypia, absent-rare mitotic figures but diffuse staining by p16, Ki67 & ProExC. HPV DNA was detected in 5 of 8 cases: only 1 was A9-positive/HPV16-positive; 1 A5/A6-positive; 1 A7-positive/not-HPV18; & 2 A9-positive/not-HPV16. 3 remaining cases demonstrated sufficient DNA to be analyzed by Inv, but results were negative.
Conclusions: There is a poorly-recognized unusual group of cervical HSIL simulating atypical metaplasia that is easily confused by histology. Immunostains prove the high-grade nature of these lesions & Inv demonstrates association with HPV types other than 16/18 (ie. other HPV types detected by Inv). We are uncertain if this group represents a HSIL-variant or an early form of classic HSIL. In one case of classic HSIL, a focus of this deceiving HSIL was present, suggesting this group may represent an early form of classic HSIL. This study emphasizes that HPV screening should not be limited to HPV 16/18 alone since this deceiving form of HSIL appears to be caused by HPV-not-16/18.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 155, Monday Morning