Thin variant of high‐grade squamous intraepithelial lesion – relationship with high‐risk and possibly carcinogenic human papilloma virus subtypes and somatic cancer gene mutations

AIM: To further characterise the thin variant of high-grade squamous intraepithelial lesions (HSILs) of the cervix defined by the World Health Organization as full-thickness HSILs with nine or fewer cell layers. METHODS AND Thin HSILs were typically solitary lesions, located at the squamocolumnar junction (20/31; 65%), in the endocervical columnar epithelium (6/31; 19%), and in both locations (5/31; 16%). The horizontal extension of thin HSILs ranged from 100 µm to 8 mm, with 30% being <1 mm. HPV data were available for 27 specimens. Twenty of 27 (74%) thin HSILs showed high-risk HPV subtypes: HPV16 (n = 8), HPV16 with coinfection (n = 2), HPV18 (n = 1), HPV31 (n = 1), HPV33 (n = 2), HPV52/58 (n = 2), and 'other' high-risk HPV genotypes (n = 4). Five of 27 (19%) thin HSILs showed possibly carcinogenic subtypes: HPV53 (n = 3), HPV73 (n = 1), and HPV82 (n = 1). One thin HSIL was induced by low-risk HPV6 and one by the unclassified subtype HPV44. Somatic gene mutations were not identified. CONCLUSION: Thin HSILs were typically small lesions without somatic gene mutations. Two-thirds of thin HSILs developed after a transforming infection with high-risk HPV subtypes, and one-third were induced by non-high-risk HPV subtypes. If cervical cancer screening relies solely on presently available clinical HPV DNA tests, a significant percentage of women with HSIL will be missed.