High risk patients with unsatisfactory anal cytology are not "negative". At least one-third proved to be concomitantly HR-HPV DNA positive with one-fifth showing subsequent cytologic squamous abnormalities and with more than 5% being diagnosed with a high grade intraepithelial lesion within two years. Prompt repeat cytology and/or HR-HPV DNA is recommended for high risk patients with non-diagnostic cytology.

Elongation factor 3 (EF3) is considered a promising drug target for the control of fungal diseases because of its requirement for protein synthesis and survival of fungi and a lack of EF3 in the mammalian host. However, EF3 has been characterized only in ascomycete yeast. In order to understand the role of EF3 in a basidiomycete yeast, we cloned the gene encoding EF3 from Cryptococcus neoformans (CnEF3), an important fungal pathogen in immunocompromised patients, including those infected with human immunodeficiency virus. CnEF3 was found to encode a 1,055-amino-acid protein and has 44% identity with EF3 from Saccharomyces cerevisiae (YEF3). Expressed CnEF3 exhibited ATPase activity that was only modestly stimulated by ribosomes from S. cerevisiae. In contrast, CnEF3 showed tight binding to cryptococcal ribosomes, as shown by an inability to be removed under conditions which successfully remove Saccharomyces EF3 from ribosomes (0.5 M KCl or 2 M LiCl). CnEF3 also poorly complemented a YEF3 defect in a diploid null mutant and two temperature-sensitive mutants which have been shown previously to be complemented well by EF3 from other ascomycetes, such as Candida albicans. These data clearly identify the presence of a functioning EF3 in the basidiomycete yeast C. neoformans, which demonstrates an evolutionary divergence from EF3 of ascomycete yeast.Cryptococcus neoformans is an important fungal pathogen which causes a lethal meningoencephalitis in a significant number of persons with AIDS and afflicts an increasing number of immunocompromised patients on steroids, chemotherapy, or posttransplant immunosuppressives (18). Therapy of cryptococcosis is limited by toxicity of such agents as amphotericin B (1); newer agents such as the azole inhibitors are less toxic, but increasing reports of resistance may limit their eventual usefulness (3,15,17). Echinocandins and pneumocandins are important new antifungal agents which are inhibitors of 1,3-␤-glucan synthetases and show excellent activity against ascomycete pathogens such as Candida albicans and Aspergillus fumigatus, but alterations in this enzyme from basidiomycetes make this important class of agents ineffective against C. neoformans (27). The latter example shows the potential gap in antifungal coverage which may occur when inhibitors are chosen without consideration of possible evolutionary differences in drug targets within various fungal pathogens.Elongation factor 3 (EF3) has been shown to be a required translation cofactor in the ascomycete Saccharomyces cerevisiae (7). The factor is also present in a variety of pathogenic ascomycete fungi, including Candida albicans (8) and the pathogen Pneumocystis carinii (34), which has been shown to be closely related to ascomycete yeasts based on analysis of its rRNA gene as well as genes encoding dihydrofolate reductase, thymidylate synthetase, ␤-tubulin, and ATP (for a review, see reference 31). While an anti-EF3 antibody has been shown to react with basidiomycete yeasts (4), EF3 has not been characterized from this cl...

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