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In the 1940s George Papanicolaou divided cytologic findings on stained cervical smears into five classes, ranging from I (normal) to V (carcinoma). Classes II through IV represented increasing degrees of premalignant squamous cellular atypia. Later workers modified the system by introducing the terms dysplasia (mild, moderate, severe) and cervical intraepithelial neoplasia (CIN) (grades 1 through 3). Papanicolaou (Pap) smear findings reported according to this nomenclature showed poor reproducibility between observers and even between separate readings by the same observer. In addition, there was little correlation between diagnostic categories and treatment options. In 1988 the National Cancer Institute sponsored a workshop in Bethesda, Maryland, to establish a more useful system. The Bethesda system was first used in 1991 and soon became standard throughout the world. Several revisions were made in 2001. The standard format for reporting cervical cytology findings according to the Bethesda system comprises three elements: 1. a statement of the adequacy of the specimen for examination (satisfactory or unsatisfactory); 2. general categorization (negative for intraepithelial lesion or malignancy; epithelial cell abnormality; or other); and 3. descriptive diagnosis, elaborating on the general categorization and including mention of all significant abnormalities, as well as of the patients hormonal status (when vaginal cells are present in the smear). A specimen that is negative for an intraepithelial lesion or malignancy may be reported as showing evidence of pathogenic organisms (for example, Trichomonas, Candida, cellular changes consistent with herpes simplex virus infection) or of nonneoplastic tissue changes (for example, inflammation, atrophy). Epithelial cell abnormalities may involve either squamous or glandular cells. The system replaces numeric designations with descriptive diagnoses of cellular changes. Squamous cell changes formerly called mild dysplasia or CIN 1, including cellular atypia characteristic of human Papillomavirus (HPV) infection, are designated low-grade squamous intraepithelial lesion (LSIL). The category of high-grade squamous intraepithelial lesion (HSIL) encompasses what were formerly called moderate and severe dysplasia or CIN 2 and CIN 3. Cytologic changes that suggest a squamous intraepithelial lesion but are quantitatively or qualitatively insufficient for a definitive interpretation are divided into atypical squamous cells of undetermined significance (ASC-US) and those with changes suggestive but not diagnostic of high-grade squamous cell intraepithelial lesions (ASC-H). It is estimated that 50 million Pap smears are performed annually in the U.S., of which 5-10% are reported as showing either ASC-US or ASC-H. In women with ASC-US, testing for high-risk HPV types by DNA probe is more sensitive than repeat thin-layer Pap smear in detecting high-grade lesions or cancer. The finding of ASC-H, LSIL, or HSIL is an indication for colposcopy and directed biopsy.