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Thin variant of high‐grade squamous intraepithelial lesion – relationship with high‐risk and possibly carcinogenic human papilloma virus subtypes and somatic cancer gene mutations
Author(s) -
Regauer Sigrid,
Reich Olaf,
Kashofer Karl
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13869
Subject(s) - pathology , cancer , cervix , cervical cancer , lesion , genotyping , hpv infection , biology , medicine , genotype , gene , genetics
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 results We examined 31 excisional cervical specimens featuring exclusively p16 INK4a ‐overexpressing thin HSILs with respect to size, location at the squamocolumnar junction or endocervical mucosa, human papilloma virus (HPV) subtypes (pretherapeutic clinical HPV tests and HPV genotyping on lesional tissue after excision), and somatic mutations in 50 cancer genes. 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.