Disagreement persists about the superiority of Reagan and Ng's method over that of Broders' for the histologic grading of squamous carcinoma of the cervix. Uncertainty about the predictive value and reproducibility of any of the grading methods prompted a comparison of factors previously suggested as indicating the biologic behavior for cervical squamous carcinoma. One hundred ninety‐five women, who were enrolled in a Gynecologic Oncology Group treatment protocol of Stage IB squamous carcinoma of the cervix and underwent radical hysterectomy with pelvic and paraaortic node sampling, formed the study population. The tumors were graded first by participating institutional pathologists, with submitted slides subjected to an independent review by two pathologists (R.J.Z. and S.W.). The histologic parameters examined included the presence and amount of keratinization, nuclear pleomorphism, mitotic rate, gestalt grading, pattern of invasion at the stromal interface, and inflammatory cell infiltrate. The depth of invasion and presence or absence of vascular invasion also were assessed. The probability of pelvic lymph node metastasis and the progression‐free interval were determined for each parameter. Surprisingly, none of the grading methods was effective in predicting nodal spread or progression‐free interval. However, an increasing depth of invasion strongly correlated with nodal spread and a diminished progression‐free interval (P < 0.0001). Vascular invasion was less effective in these predictions (0.05 < P < 0.10). Both measurements were reasonably reproducible. It was concluded that histologic grading of surgically treated cervical carcinoma is not useful but that the depth of invasion and vascular invasion are important predictors of behavior that should be reported routinely.

These studies represent the first analysis of viable mononuclear cells isolated from normal cervical tissue. The results form a baseline from which it will now be possible to compare changes that occur at the cervical squamocolumnar junction in response to infection or neoplasia.

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Forty-seven young women with mild or moderate dysplasia of the uterine cervix (cervical intraepithelial neoplasia) diagnosed by cervical smears, received oral supplements of folic acid, 10 mg, or a placebo (ascorbic acid, 10 mg) daily for 3 months under double-blind conditions. All had used a combination-type oral contraceptive agent for at least 6 months and continued it while returning monthly for follow-up examinations. All smears and a biopsy obtained at the end of the trial period were classified by a single observer without knowledge of treatment status using an arbitrary scoring system (1 normal, 2 mild, 3 moderate, 4 severe, 5 carcinoma in situe). Mean biopsy scores from folate supplemented subjects were significantly better than in folate-unsupplemented subjects (2.28 versus 2.92, respectively; p less than 0.05). Final versus initial cytology scores were also significantly better in supplemented subjects (1.95 versus 2.32, respectively; p less than 0.05), unchanged in patients receiving the placebo (2.27 versus 2.30, respectively). Before treatment the mean red cell folate concentration was lower among oral contraceptive agent users than nonusers (189 versus 269 ng/ml, respectively; p less than 0.01) and even lower among users with dysplasia (161 versus 269 ng/ml, respectively; p less than 0.001). Morphological features of megaloblastosis were associated with dysplasia and also improved in folate supplemented subjects. These studies indicate that either a reversible, localized derangement in folate metabolism may sometimes be misdiagnosed as cervical dysplasia, or else such a derangement is an integral component of the dysplastic process that may be arrested or in some cases reversed by oral folic acid supplementation.