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The histologic criteria for reactivereparative lesions and precursor lesions (squamous intraepithelial lesions; SIL) of the cervix are established, but a proportion of cervical biopsies contains squamous epithelial alterations that do not fall into either category (nondiagnostic squamous atypia or atypical squamous epithelium of undetermined significance). This study examined (a) the degree to which this diagnosis could be made consistently between two experienced pathologists and (b) its relationship to papillomavirus nucleic acids. One author selected 37 cervical biopsies with a spectrum of cellular changes occurring in the context of inflammatory or reactive epithelial changes, and each case was reviewed by two pathologists independently and classified as reactive, nondiagnostic atypia, and diagnostic (SIL). Concordance between two observers was highest for a diagnosis of SIL (kappa 0.68), followed by reparativereactive (kappa 0.48). Concordance for a designation as nondiagnostic squamous atypia was fair (kappa 0.39). Seven of 37 (19) cases were HPV positive, including 27, 519, and 011 cases designated by at least one observer as SIL, nondiagnostic squamous atypia, or neither (i.e., both reactive), respectively. The findings support a category of nondiagnostic squamous atypia but emphasize the value of a second observer and possibly, HPV DNA testing, in resolving such cases. Similarities in HPV positivity between nondiagnostic atypia and SIL in this study may reflect problems of both criteria selection and consistent application of these criteria in a setting of reactive/reparative changes.

Mutation or overexpression of certain host genes, including c-myc, Ha-ras, and Ki-ras, have been associated with genital squamous neoplasia, specifically in the cervix, and have been implicated in the natural history of these tumors. The relationship of these host gene alterations to vulvar squamous cell carcinomas has not been previously studied. We analyzed archival material from 13 human papillomavirus-positive and-negative vulvar squamous cell carcinomas for mutations in Ha-, Ki-, and N-rasgenes, and a smaller number of flesh samples for c-mycamplification, using PCR-based assays. For comparison, eight cervical squamous cell carcinomas (three fixed and five fresh) were also analyzed. Analysis for ras mutations revealed a previously reported silent allelic variant at nucleotide 1744 in the Ha-ras gene, but no mutations in codons 12, 13, or 61. Similarly, genomic amplification of c-mycbeyond a maximum of three haploid copies was not identified in the cases. These findings indicate that alterations in mycor ras sequences are not linked to vulvar squamous cell carcinomas or to the presence or absence of HPV nucleic acids. Moreover, they apparently will not distinguish vulvar from cervical carcinomas, both groups appearing to be unlikely to harbor these sequence alterations.

Human papillomavirus (HPV) has long been recognized as the etiologic agent of skin and genital warts, and only recently has an oncogenic role been attributed to the virus. This article discusses the classification, genetics, and pathogenesis of HPV. HPV detection, epidemiology of HPV and cervical neoplasia, and HPV infections in the genital tract are also reviewed.