Kristin A. Keefe

HPV infection and number of lifetime sexual partners are strong predictors for 'natural' regression of CIN 2 and 3

The aim of this paper was to evaluate the factors that predict regression of untreated CIN 2 and 3. A total of 93 patients with colposcopic persistent CIN 2 and 3 lesions after biopsy were followed for 6 months. Human papillomavirus (HPV) types were determined by polymerase chain reaction at enrolment. We analysed the biologic and demographic predictors of natural regression using univariate and multivariate methods. The overall regression rate was 52% (48 out of 93), including 58% (22 out of 38) of CIN 2 and 47% (26 out of 55) of CIN 3 lesions (P=0.31 for difference). Human papillomavirus was detected in 84% (78 out of 93) of patients. In univariate analysis, 80% (12 out of 15) of lesions without HPV regressed compared to 46% (36 out of 78) of lesions with HPV infection (P=0.016). Women without HPV and those who had a resolution of HPV had a four-fold higher chance of regression than those with persistent HPV (relative odds=3.5, 95% CI=1.4–8.6). Women with five or fewer lifetime sexual partners had higher rates of regression than women with more than five partners (P=0.003). In multivariate analysis, HPV status and number of sexual partners remained as significant independent predictors of regression. In conclusion, HPV status and number of lifetime sexual partners were strongly predictive of regression of untreated CIN 2 and 3.

Atypical glandular cells of undetermined significance in cervical cytologic findings

OBJECTIVE Our purpose was to increase our understanding of the clinical significance of atypical glandular cells of undetermined origin. STUDY DESIGN All cytologic Papanicolaou smears were reviewed and classified within the context of the Bethesda classification system. Charts of all patients with a diagnosis of atypical glandular cells of undetermined origin were reviewed for previous medical history, diagnostic study, histologic diagnosis, and prior Papanicolaou smear abnormalities. RESULTS The incidence of atypical glandular cells of undetermined origin in 76,018 Papanicolaou smears was 0.196%. We reviewed 133 patient medical records with cytologic diagnoses. Eighty of these patients have had appropriate follow-up. Thirty-six (45%) of these were found to have significant histologic abnormalities, including 6 patients with cervical intraepithelial neoplasia, grades 2 and 3, and 4 invasive cancers. CONCLUSION The frequency of underlying serious histologic changes is much greater in atypical glandular cells than in atypical squamous cells of undetermined significance. On the basis of our results, we believe that all patients with atypical glandular cells should undergo intensive evaluation including colposcopy, cervical biopsy, and endocervical curettage. When diagnosis cannot be clearly established, patient should undergo endometrial biopsy.

m‐THPC‐Mediated Photodynamic Therapy (PDT) Does Not Induce Resistance to Chemotherapy, Radiotherapy or PDT on Human Breast Cancer Cells In Vitro

Photodynamic therapy (PDT) uses laser light to activate a photosensitizer that has been absorbed preferentially by cancer cells after systemic administration. A photo‐toxic reaction ensues resulting in cell death and tissue necrosis. Some cells, however, may survive PDT. This study was performed to determine if surviving human breast cancer cells (MCF‐7) can become resistant to PDT, chemotherapy or radiotherapy. The MCF‐7 cells were cultured under standard conditions prior to being exposed to the photosensitizer, 5,10,15,20‐meta‐tet‐ra(hydroxyphenyl)chlorin (zn‐THPC), for 24 h and then irradiated with laser light (652 nm). Surviving cells were allowed to regrow by allowing a 2 week interval between each additional PDT. After the third and final treatment, colony formation assays were used to evaluate the sensitivity of cultured cells to ionizing radiation and PDT and the ATP cell viability assay tested in vitro chemosen‐sitivity. Flow cytometry was used to analyze the cell cycle. No alterations in the cell cycle were observed after three cycles of PDT with m‐THPC. Similar responses to chemotherapy and ionizing radiation were seen in control and treatment groups. The m‐THPC‐sensitized PDT did not induce resistance to subsequent cycles of PDT, chemo‐ or radiotherapy. Photodynamic therapy with m‐THPC may represent a novel adjunctive treatment of breast cancer that may be combined with surgery, chemotherapy or ionizing radiation.

Influence of serum and tissue micronutrient levels on the regression of untreated cervical intraepithelial neoplasia 2 and 3.

Objective. To determine the influence of micronutrient levels on the regression of untreated cervical intraepithelial neoplasia (CIN). Materials and Methods. Serum and vaginal washings were analyzed for micronutrient levels at the time of diagnosis and after 6 months of observation. Serum and vaginal levels of &bgr;-carotene, vitamin E, and retinol were correlated with spontaneous regression, persistence, or progression of CIN. Regression was defined as resolution of the lesion by 2 or more grades (CIN 2 to normal and CIN 3 to CIN 1 or normal). Wilcoxon signed rank, Wilcoxon rank sum, and Spearman correlation were used for data analysis. Results. The overall regression rate was 52% (48/93), including 58% (22/38) of CIN 2 and 47% (26/55) of CIN 3 lesions. The median baseline serum levels for &bgr;-carotene, vitamin E, and retinol among those whose lesions regressed were 161 ng/mL, 10,554 ng/mL, and 446 ng/mL, respectively, whereas levels among patients with persistence or progression were 128 ng/mL, 10,286 ng/mL, and 503 ng/mL, respectively. These differences were not statistically significant. The median serum level of &bgr;-carotene at 6 months among patients whose lesions regressed was 456 ng/mL compared with 956 ng/mL among the patients with progression or persistence (p = .38). Vaginal levels of &bgr;-carotene correlated with serum levels; however, they were also not predictive of CIN regression. Conclusion. Micronutrient levels are not predictive of CIN regression.