Predictors of human papilloma virus in patients with keratinization

Given the prevalence of human papilloma virus (HPV) infection, an attempt was made to determine whether certain factors such as keratinization and/or squamous atypia are associated with its development. Review of our gynecologic cytology files from 1989 yielded 1,615 specimens showing parakeratosis and/or hyperkeratosis, without cytologic evidence of HPV. Concomitant diagnoses included no atypia [keratinization only (KO)], inflammatory squamous atypia (ISA), and squamous atypia (SA). Morphologic follow-up including repeat cytology or biopsy was available for 916 cases, 92 (10.0%) of which possessed changes of HPV. For any case with both cytologic and biopsy evidence of HPV, only the biopsy result was tabulated. HPV on follow-up examination was detected in 52 (6.7%) of the 764 cases with KO; in 20 (20.8%) of the 96 cases with keratinization and ISA (KISA); and in 20 (35.7%) of the 56 cases with keratinization and SA (KSA). The definitive diagnosis of HPV was based on previously described features (Gupta, In: Comprehensive Cytopathology, Philadelphia: WB Saunders, 1991:133-140) including nuclear enlargement with nuclear membrane irregularities in combination with sharply demarcated paranuclear cytoplasmic clearing. Affected cells have rounded borders. Binucleated cells are not uncommon. The increasing percentage of HPV from KO to KISA to KSA is not necessarily surprising. However, mathematical analysis revealed statistically significant differences in the development of HPV in each of the 3 groups: KISA vs. KO (P < 0.001), KSA vs. KO (P < 0.001), and KSA vs. KISA (P < 0.05). Therefore, a cytologic diagnosis of keratinization with ISA or especially SA should warrant closer follow-up than that of KO.