Thin variant of high grade squamous intraepithelial lesion - relationship to high risk and possibly carcinogenic HPV subtypes and somatic cancer gene mutations.

AIM: To further characterize the thin variant of high grade squamous intraepithelial lesion (HSIL) of the cervix defined by the WHO as full thickness HSIL <9 cell layers.

METHODS: We examined 31 excisional cervical specimens featuring exclusively p16ink4a over-expressing thin HSIL with respect to size, location at squamo-columnar junction or endocervical mucosa, human papilloma virus (HPV) subtypes (pre-therapeutic clinical HVP-tests and HPV-genotyping on lesional tissue after excision) and somatic mutations in 50 cancer genes.

RESULTS: Thin HSIL were typically solitary lesions, located at the squamo-columnar junction (20/31; 65%), in endocervical columnar epithelium (6/31; 19%) and in both locations (5/31; 16%). The horizontal extension of thin HSIL ranged from 100μm-8mm, with 30% being smaller than 1mm. HPV-data were available for 27 specimens. 20/27 (74%) thin HSIL revealed high-risk-HPV subtypes: HPV16 (n=8), HPV16 with coinfection (n=2), HPV18 (n=1), HPV31 (n=1), HPV33 (n=2), HPV 52/58 (n=2), "other" high-risk-HPV genotypes (n=4). 5/27 (19%) thin HSIL revealed possibly carcinogenic subtypes HPV53 (n=3), HPV73 (n=1), and HPV82 (n=1). One thin HSIL each was induced by low-risk HPV6 and not classified subtype HPV44. Somatic gene mutations were not identified.

CONCLUSION: Thin HSIL were typically small lesions without somatic gene mutations. Two thirds of thin HSIL developed after a transforming infection with high risk HPV-subtypes, and one third was induced by non-high-risk HPV-subtypes. If cervical cancer screening would rely solely on presently available clinical HPV DNA tests a significant percentage of women with HSIL will be missed. This article is protected by copyright. All rights reserved.