Given the prevalence of human papilloma virus (HPV) infection, an atte
mpt was made to determine whether certain factors such as keratinizati
on and/or squamous atypia are associated with its development. Review
of our gynecologic cytology files from 1989 yielded 1,615 specimens sh
owing 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). M
orphological follow-up including repeat cytology or biopsy was availab
le for 916 cases, 92 (10.0%) of which possessed changes of HPV. For an
y 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 ke
ratinization and ISA (KISA); and in 20 (35.7%) of the 56 cases with ke
ratinization and SA (KSA). The definitive diagnosis of HPV was based o
n previously described features (Gupta, In: Comprehensive Cytopatholog
y, Philadelphia: WB Saunders, 1991:133-140) including nuclear enlargem
ent with nuclear membrane irregularities in combination with sharply d
emarcated paranuclear cytoplasmic clearing. Affected cells have rounde
d borders. Binucleated cells are not uncommon. The increasing percenta
ge of HPV from KO to KISA to KSA is not necessarily surprising. Howeve
r, mathematical analysis revealed statistically significant difference
s 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 sh
ould warrant closer follow-up than that of KO. (C) 1995 Wiley-Liss, In
c.