A comprehensive evaluation of the accuracy of cervical pre-cancer detection methods in a high-risk area in East Congo.

BACKGROUND: Given the high burden of cervical cancer in low-income settings, there is a need for a convenient and affordable method for detecting and treating pre-cancerous lesions. METHODS: Samples for comparing the accuracy of cytology, virology and histology were collected. Identification of HPV E6/E7 mRNA was performed using PreTect HPV-Proofer. HPV DNA detection was performed by GP5+/6+ PCR, followed by reverse line blot (RLB) for typing. RESULTS: A total of 343 women, aged 25-60 years, attending gynaecological polyclinics in DR Congo were included for sample enrolment. The test positivity rate was conventional and liquid-based cytology (LBC) at cutoff ASCUS+ of 6.9 and 6.6%, respectively; PreTect HPV-Proofer of 7.3%; and consensus DNA PCR for 14 HR types of 18.5%. Sixteen cases of CIN2+ lesions were identified. Of these, conventional cytology identified 66.7% with a specificity of 96.2%, LBC identified 73.3% with a specificity of 96.9%, all at cutoff ASCUS+. HR-HPV DNA detected all CIN2+ cases with a specificity of 85.9%, whereas PreTect HPV-Proofer gave a sensitivity of 81.3% and a specificity of 96.6%. CONCLUSION: Both HPV detection assays showed a higher sensitivity for CIN2+ than did cytological methods. Detecting E6/E7 mRNA from only a subset of HR HPVs, as is the case with PreTect HPV-Proofer, resulted in a similar specificity to cytology and a significantly higher specificity than consensus HR HPV DNA (P<0.0001).

Prognostic factors in patients with stage I epithelial ovarian cancer.

We analyzed factors predictive of relapse risk in patients with stage I invasive epithelial ovarian cancer: 252 patients from the Princess Margaret Hospital provided a data base for hypothesis generation, and data on 267 patients from the Norwegian Radium Hospital were used for hypothesis testing. The outcomes in most analyses in the two series were very similar, validating the following conclusions. Differentiation (grade) was the most powerful predictor of relapse, followed by dense adherence (which resulted in outcomes equivalent to those in stage II) and, finally, large-volume ascites. When the effects of these three factors were accounted for, then none of the following were prognostic: bilaterality (stage Ib), cyst rupture (stage Ic), capsular penetration (stage Ic), tumor size, histologic subtype, patient age, year of diagnosis, and postoperative therapy. These results allow simplification of stage I substaging, as only differentiation, dense adherence, and large-volume ascites (? peritoneal cytology) need be considered. The 5-year relapse-free rate was 98% in patients with grade 1 tumors in whom both dense adherence and large-volume ascites were absent. These patients are adequately treated by operation alone. Although the relapse risk was high enough in the remaining patients to warrant postoperative treatment, a significant benefit could be shown only for a small subset of patients, namely those with densely adherent tumors treated with abdominopelvic radiotherapy. In grades 2 and 3, none of the therapies used in either series was superior to pelvic radiotherapy or operation alone.

Human T cell response to Herpes simplex virus antigen in vitro.

Herpes simplex virus type I antigen (HSV-Ag) added to T cells from individuals with clinical history of recurrent herpes labialis causes a proliferative response in vitro. This T cell response requires presensitization of the responding cell donor and will occur only in the presence of adherent cells (macrophages). The intensity of the response is closely related to the number of adherent cells present, being optimal at a ratio of 10:1 between T cells and adherent cells. Preliminary studies also indicate that the response to HVS-Ag is restricted by the HLA-D/DR determinants of the T cell donor.

The proliferative T cell response to herpes simplex virus (HSV) antigen is restricted by self HLA-D.

T cells from sensitized individuals react with a proliferative response to herpes simplex virus antigen (HSV-Ag) in vitro, when antigen is presented together with autologous macrophages (Mø). We here report that this T-Mø co-operation is restricted by self HLA-D/DR molecules of the sensitized T cell donor. Furthermore, it is shown that the lack of co-operation between T cells and HLA-D/DR disparate macrophages, is due neither to suppression nor to generation of cytotoxic T cells in the allogeneic mixture.

Both DR and MT class II HLA molecules may restrict proliferative T-lymphocyte responses to antigen.

Antigen-primed T-cell blasts may be separated from alloreactive T cells on Percoll gradients. By means of this method, HLA restriction of antigen-specific proliferative T-cell responses may be studied, using allogeneic antigen-presenting cells carrying foreign D/DR antigens. The reported data confirm that the D/DR molecules as such are major restriction elements in the T-cell response to herpes simplex virus (HSV) and purified protein derivative (PPD). However, evidence is presented that other Class II HLA molecules, the MT molecules, may also function as restriction elements for the HSV response.

HLA-D/DR restriction of Langerhans cell-dependent antigen activation of T lymphocytes. The same D/DR determinants are restriction elements on monocytes and Langerhans cells.

In previous studies we have shown that the response of T cells to antigen presented by epidermal Langerhans cells (LC) is restricted by products of the HLA-D region. An optimal antigen-specific response required that the LC used for antigen presentation shared both, or at least one, of the D/DR determinants of the T-cell donor. These studies were, however, disturbed by a strong allogeneic response induced by the foreign D/DR determinants of the LC. We report here that by separating the antigen-specific T cells from those that are alloreactive, a clearer picture of the D/DR restriction phenomenon may be obtained. Furthermore, the present studies demonstrate that the same D/DR determinants function as restriction elements on peripheral blood monocytes and LC.

HLA-D/DR restriction of proliferative T cell responses to antigen. Enrichment of antigen-specific T cell blasts and evidence of preferential HLA-D/DR restriction.

Antigen-specific T cell blasts may be separated from alloreactive cells on Percoll gradients. The absence of alloreactivity allowed us to study HLA-D/DR restriction of proliferative T cell responses towards PPD and HSV antigens using allogeneic antigen-presenting cells. An overriding impact of self HLA-D/DR determinants as restriction elements for in vivo sensitized T cells was demonstrated. Furthermore, evidence was obtained that the proliferative PPD response might be preferentially restricted by HLA-D/DR 1.