[1249] Expression of p16 in Low-Grade Squamous Intraepithelial Lesions (LSIL/CIN 1): Correlation of Immunohistochemical Staining Patterns with Analysis of Human Papillomavirus (HPV) Types

Anna Yemelyanova, Brigitte M Ronnett, Jeffrey D Seidman, Aleksandra Ogurtsova, Patti E Gravitt. Johns Hopkins University, Baltimore, MD

Background: Immunohistochemical analysis of p16 expression is currently recommended to distinguish precancer (high-grade squamous intraepithelial lesion, [HSIL/CIN2 and CIN3]) and mimics of HSIL (immature squamous metaplasia, atrophy, reparative epithelial changes), with diffuse strong staining supporting a diagnosis of HSIL. P16 is also recommended when a diagnosis of HSIL/CIN 2 is being considered, with downgrading to LSIL/CIN 1 when negative/patchy and upgrading to HSIL/CIN 2 when diffuse. However, a subset of adjudicated LSIL is known to have diffuse p16 expression but the data regarding HPV typing of these lesions is lacking. This study correlates p16 expression patterns in LSILs with HPV types.
Design: One hundred ninety-nine cervical specimens were diagnosed as LSIL by 2 pathologists. Immunohistochemical staining for p16 was scored as positive (diffuse/strong band-like staining in at least the lower third of the epithelium) or negative (either absent or focal/patchy staining throughout the entire lesion). HPV typing was performed on the same tissue block.
Results: 117 (59%) LSILs were positive for p16, 48 (24%) were negative, and 34 (17%) demonstrated a mixed pattern of staining with discrete foci of positive and negative/patchy expression within the lesion. Multiple HPV types were detected in 136 (69%) cases. In one case that had no HPV detected, p16 was negative. Data are summarized in Table 1.

Table 1. Patterns of p16 expression and distribution of HPV types in LSILs
HPV types (n)P16 expression pattern
 Positive (%)Negative (%)Mixed pattern (%)
HRHPV only (107)74 (69%)18 (17%)*15 (14%)
LRHPV only (11)0 (0%)11 (100%)0 (0%)
HRHPV and LRHPV (47)24 (51%)14 (30%)9 (19%)
HRHPV and HPV of uncertain risk (29)17 (59%)2 (7%)10 (34%)
LRHPV and HPV of uncertain risk (1)0 (0%)1 (100%)0 (0%)
HPV of uncertain risk only (3)2 (67%)1 (33%)0 (0%)
Total (198)117 (59%)47 (24%)34 (17%)
HRHPV - high-risk HPV; LRHPV - low-risk HPV; *The HRHPV types detected in this group included most commonly HPV 51, 52, 66, 68, 82; occasionally HPV 35, 39; rarely HPV 16, 18 (one case each)

Conclusions: Diffuse/strong p16 expression is observed in a significant proportion of LSILs (59%). While positive p16 expression in LSIL is strongly correlated with the presence of HRHPV (98%), a subset of p16-negative LSILs (17%) also contains HRHPV types only. However, the latter group commonly contains HRHPV types other than 16 and 18. Detailed HPV typing using in situ hybridization is required for type attribution in specimens with multiple HPV types.
Category: Gynecologic & Obstetrics

Tuesday, March 5, 2013 8:30 AM

Proffered Papers: Section E, Tuesday Morning


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