Coexistence of low and high grade squamous intraepithelial lesions of the cervix: morphologic progression or multiple papillomaviruses?

BACKGROUND

The diagnosis of both low (LSIL) and high (HSIL) grade squamous intraepithelial lesions in the same cervical specimen may reflect classification variation, morphologic progression in situ, and, conceivably, different HPV infections. We addressed these possibilities in cervical specimens previously diagnosed as containing both LSIL (condyloma/CIN1) and HSIL (CIN2/3).

METHODS

All cases with a histologic diagnosis of LSIL and HSIL from 1994-1996 were reviewed. On review, lesions were scored as (1) no significant variation in lesion grade (classification discrepancies) and showing a (2) one (CIN1-2) or (3) two (CIN1-3) grade shift in the same case. In cases in which a one or two grade shift was confirmed, low (CIN1) and high (CIN2-3) grade foci were microdissected and extracted DNA analyzed for HPV by PCR and RFLP analysis.

RESULTS

Of 98 cases available for review, 58 (59%) did not exhibit significant variation in grade (classification discrepancy), and 40 (41%) showed a one (25) or two (15) grade shift. Of the latter group both LSIL and HSIL foci were HPV(+) in 26 (65. 0%). The same HPV was present in both LSIL and HSIL foci in 15/15 lesions with a one grade shift (CIN1-2). In contrast, a significantly higher proportion of lesions with a two grade shift (CIN1-3) contained two different HPV types (4/11 vs 0/15; P = 0.01). Combinations of HPVs in the low/high grade foci, respectively, included HPV 11/16 (1), 11/16 + 18 (1), and HPV39/16 (2).

CONCLUSIONS

Lesions containing LSIL and HSIL which span two grades (CIN1 and CIN2) most likely represent morphologic progression in a single infection. Lesions containing CIN1 and CIN 3 may be attributed to both lesion progression and two coincident infections; the latter sometimes present in the same histologic section. The latter phenomenon has implications for both the diagnosis of CIN and interpretation of "morphologic progression" from very low to high grade in the same case.