Grading the severity of cervical neoplasia based on combined histopathology, cytopathology, and HPV genotype distribution among 1,700 women referred to colposcopy in Oklahoma

Diagnosis and treatment of cervical cancer precursors rely on colposcopic biopsy, which is sometimes [tampered by incorrect biopsy placement an the unclear prognostic value of poorly reproducible diagnoses such as cervical intraepithelial neoplasia WIN) Grade 1 and 2. Searching for discrete disease categories that incorporate the value or cytology and that reflect the causal role of particular HPV types, we analyzed histology, cytology and HPV genotype distributions in the Study to Understand Cervical Cancer Endpoints and Early Determinants (SUCCEED). This cross-sectional study comprises similar to 1,700 women referred to colposcopy or treatment for the spectrum of cervical disease, including 439 women with <CIN1, 429 CIN1, 322 CIN2, 297 CIN3 and 107 with cancer. Using hierarchical clustering of histology-cytology groups based on HPV genotype distributions, we could plainly, distinguish in this referral population 5 increasingly severe diagnostic groups of HPV-positive women: (i) HPV-positive women with <CIN2 histology and normal cytology, (h) HPV positive women with <CIN2 histology and ASC or LSIL cytology; Wit CIN2, including histologic CIN2 and HSIL cytology with any histology <CIN2; (it,) CIN3, and on invasive cervical cancer. The grouping of women with HSIL cytology, but without histological abnormalities to women with CIN2 suggests that in these cases the worst lesion wits missed during colposcopy-biopsy. We are now using these sharpened diagnostic categories to search for novel biomarkers predicting the risk of progression and invasion. (C) 2008 Wiley-Liss, Inc.