Cervical cancer disparities in South Carolina: an update of early detection, special programs, descriptive epidemiology, and emerging directions.

Through careful examination of cervical cancer incidence and mortality rates and current resources available in South Carolina, we have identified research and intervention priorities related to cervical cancer that would best serve the women of this state. Mortality rates due to cervical cancer are largely explained by the lack of early detection among women rarely and never screened and non-adherence to recommended follow-up care of cervical dysplasia; however, other factors less well explained are determinants of observed disparities between AA and EA women. Efforts are underway to implement strategies recommended by the NCI to eliminate cervical cancer disparities through improved efforts to reach out to rarely and never-screened women and prepare health care providers for implementation of HPV vaccines.

Early non-invasive diagnosis of cervical cancer: beyond Pap smears and human papilloma virus (HPV) testing.

Cervical cancer is a major gynecologic malignancy around the world. However, current diagnostic methods such as Pap smear and human papilloma virus (HPV) testing are insufficient for an early diagnosis of cervical cancer, follow-up on therapy efficacy or to identify the women who might progress to cervical cancer (only about 1-5% of the HPV-positive women will develop cervical cancer). Patients with atypical squamous cells of undetermined significance (ASC-US) clearly need a better screening test.

Serum vascular endothelial growth factor C (VEGF-C) as a specific biomarker for advanced cervical cancer: Relationship to insulin-like growth factor II (IGF-II), IGF binding protein 3 (IGF-BP3) and VEGF-A [corrected].

Objectives: An early non-invasive diagnosis of cervical cancer and its metastasis can save lives. We have shown that serum IGF-II levels can be effectively used for a specific early diagnosis of cervical cancer. Here, we shall determine if serum levels of vascular endothelial growth factors B and C (VEGF-A [corrected] VEGF-C) associated with vasculogenic and lymphogenic metastasis may be used for an early diagnosis of advanced metastatic cervical cancer and compare these levels with those of the serum IGF-II and IGF-binding protein 3 (IGF-BP3).

Vascular endothelial growth factor (VEGF) up-regulates epidermal growth factor receptor (EGF-R) in cervical cancer in vitro: this action is mediated through HPV-E6 in HPV-positive cancers.

Objectives: Epidermal Growth Factor Receptor (EGF-R) up-regulation in cervical cancer cells leads to an increase in cell proliferative Insulin-like Growth Factor II (IGF-II) and Vascular Endothelial Growth Factor (VEGF) and a decrease of the anti-proliferative IGF-binding protein-3 (IGF-BP3). The objectives for this study are: (a) to find if VEGF, in turn, up-regulates EGF-R and down-regulates IGF-BP3; (b) to determine if human papilloma virus (HPV-E6) mediates this action of VEGF in HPV-positive cells; and (c) to verify if these effects are reflected in changes in cell proliferation

Methods: We used HPV-positive HeLa (Black), ME-180 and CaSki (Caucasian) and HPV-negative HT-3 (Caucasian) cell lines. (a) Levels of HPV-E6 in the HPV-positive cells were enumerated after treating the cells for 24 h with 20 ng/ml of VEGF using our semi-quantitative immunofluorescent antibody assay.

Up-regulation of vascular endothelial growth factor-C by nicotine in cervical cancer cell lines.

Problem: Smoking and infection with human papilloma virus (HPV) are major risk factors for cervical cancer. Our earlier work shows that nicotine enhances cellular proliferation of cervical cancer cell lines by up-regulating epidermal growth factor (EGF) and its receptor EGF-R, which leads to increased insulin-like growth factor II in vitro. We found that the vascular endothelial growth factor (VEGF)-C, one of the five isoforms of VEGF, may be specifically involved in lymphogenic metastasis of cervical cancer.

Circulating levels of insulin-like growth factor-II and IGF-binding protein 3 in cervical cancer.

Objective: We aimed to further document that elevated levels of circulating insulin-like growth factor II (IGF-II) are associated with cervical cancer and to test the hypothesis that there may be an inverse association between IGF-II and IGF-binding protein 3 (IGF-BP3).

Methods: Serum IGF-II and IGF-BP3 levels were measured, using ELISA kits (Diagnostic Systems Laboratories), in 23 controls; 16 ASC-US with normal biopsies; 14 ASC-US with advanced CIN; 2 pretherapy CIN-I; 8 successfully treated CIN-I; 24 persistent CIN I; 14 pretherapy CIN II/III; 10 posttherapy CIN II/III with normal biopsies; 18 persistent CIN-II/III; 7 with pretherapy cervical cancer; 19 with posttherapy cervical cancer under remission; 15 with posttherapy persistent/recurrent cervical cancer; 10 with persistent ovarian or endometrial cancer; and 3 with endometrial or vulvar with cervical cancer. Student's t test and linear regression analysis were used.

In vitro downregulation of growth factors by insulin-like growth factor binding protein-3 in cervical cancer.

Objectives: Our hypothesis is that insulin-like growth factor binding protein 3 (IGF-BP3) would downregulate epidermal growth factor receptor (EGF-R) levels in cervical cancer cell lines, thereby reducing cellular IGF-II and angiogenesis-related vascular endothelial cell growth factor (VEGF). As folate deficiency is a risk factor in cervical cancer, we sought to determine if folic acid treatment might increase IGF-BP3 production, thereby inhibiting malignant cell proliferation.

Methods: We determined the cellular levels of EGF-R, IGF-II, and VEGF in the cervical cancer cell lines HeLa, ME-180 (both positive for human papilloma virus; HPV), and HT-3 (HPV-negative), following their treatment with IGF-BP3.

Insulin-like growth factor II in gynecological cancers: a preliminary study.

Problem: We have previously reported elevated serum levels of cervical human papilloma viral proteins E6 and E7 and serum insulin-like growth factor II (IGF-II) in women with cervical cancer and advanced cervical intraepithelial neoplasia. As most women with cervical cancer have elevated levels of serum IGF-II, we sought to determine whether the cervical cancer and lymph node biopsies from these women demonstrated increased production of IGF-II and whether this elevation was also present in ovarian and endometrial cancers.

Method Of Study: We used the semi-quantitative immunofluorescent antibody assay established in our laboratory to identify the levels of IGF-II in 21 cervical cancers (seven with matching lymph nodes), 18 benign cervical biopsies, 13 endometrial cancers, 15 benign endometrial biopsies, 5 ovarian cancers, and 15 benign ovarian biopsies.

Expression of cyclooxygenase-2 in cervical, endometrial, and ovarian malignancies.

Objective: This study was undertaken to compare the presence of cyclooxygenase-2 (COX-2) levels between normal and malignant cervix, endometrium, and ovary.

Study Design: Semiquantitative immunofluorescent assays for COX-2 were performed on sections of cervical squamous cell carcinoma (n = 12), endometrial adenocarcinoma (n = 13), and ovarian serous adenocarcinoma (n = 9). Levels of immunofluorescence for each sample were objectively measured, categorized as high, moderate, or negative expression and compared with normal cervical (n = 14), endometrial (n = 15), and ovarian (n = 13) tissue with the Fisher exact test.