These data suggest that epigenetic markers in plasma may be of interest for detection of breast cancer. Identification of additional breast cancer specific methylated genes with higher prevalence in early stage cancers would improve this approach.

To assess the risk of prevalent high-grade cervical squamous intraepithelial lesions (HSILs) or invasive cervical cancer (ICC) associated with human immunodeficiency virus (HIV) type 1, HIV-2, and human papillomavirus (HPV) infections, HIV load, and CD4 cell count, we studied 4119 women attending an outpatient clinic in Senegal. HIV infection was associated with increased rates of cervical infection with high-risk HPVs. Among women infected with high-risk HPVs, those with HIV-1 (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.0-4.8), HIV-2 (OR, 6.0; 95% CI, 2.1-17.1), or dual HIV infection (OR, 8.0; 95% CI, 2.0-31.5) were more likely to have HSILs or ICC diagnosed than were HIV-negative women; this association was not observed among women not infected with high-risk HPVs. Among women with HIV, higher HIV plasma RNA loads and lower CD4 cell counts were associated with high-risk HPV infection and degree of cervical abnormality. Furthermore, HIV-2-positive women were more likely to have HSILs (OR, 3.3; 95% CI, 0.9-12.4) or ICC (OR, 7.9; 95% CI, 1.1-57) than were HIV-1-positive women.

Aberrant promoter methylation analysis on exfoliated cell samples is a potential diagnostic tool for cervical cancer screening that potentially may be used alone or in conjunction with cytology and/or human papillomavirus testing.

Previous studies among women worldwide have demonstrated that infection with specific types of human papillomaviruses (HPV) is central to the pathogenesis of cervical neoplasia. There is little data, however, concerning the prevalence of specific HPV types and the association of each type with cervical neoplasia among women in sub-Saharan Africa, who remain at very high risk of cervical cancer. We studied 2,065 consecutive patients aged 35 years or older, presenting to community health clinics in Dakar and Pikine, West Africa, who had not been screened previously for cytologic abnormalities or HPV. Cytologic diagnosis and HPV detection were accomplished using a ThinPrep Pap and a polymerase chain reaction-based reverse-line strip assay, respectively. Odds ratios (OR) and associated 95% confidence intervals (CI) were estimated using polynomial logistic regression. Cytologic abnormalities were found in 426 women (20%), including 254 (12%) with atypical squamous cells of undetermined significance, 86 (4%) with low-grade squamous intraepithelial lesions, 66 (3%) with high-grade squamous intraepithelial lesions (HSIL) and 20 (1%) with invasive cancer. HPV infection was detected in 18%. Among women with negative cytologic findings, the prevalence of high risk but not low risk HPV types increased with age. HPV16 (2.4%) and HPV58 (1.6%) were the most frequently detected HPV types in this population, as well as being the most strongly associated with risk of HSIL/cancer (HPV16: OR ‫؍‬ 88, 95% CI ‫؍‬ 39 -200; HPV58: OR ‫؍‬ 51, 95% CI ‫؍‬ 16 -161). These data suggest that in addition to HPV16, HPV58 should be considered in the strategic planning of vaccination against cervical cancer in this geographic region. © 2002 Wiley-Liss, Inc. Key words: human papillomavirus; squamous intraepithelial lesion; AfricaGenital human papillomaviruses (HPV) are common sexually transmitted viruses and a subset, termed "high risk" types, are integral to the development of invasive cervical cancer 1,2 and its cytologic precursors, squamous intraepithelial lesions (SIL). [3][4][5] HPV16 is the most common HPV type found in the cervix and in cervical cancers, where it is detected in over 50% of cases. 6 Other HPV types detected commonly in cervical cancers include types 18, 45 and 31. 6 Development of appropriate HPV vaccines requires knowledge of the prevalence of various HPV types in neoplastic and nonneoplastic cervical lesions in populations at high risk of cervical cancer. Thus far, data concerning type-specific HPV prevalence has come primarily from studies among women in Europe and North and South America. [7][8][9][10][11][12] Although there appears to be little geographic variation in the prevalence of HPV16, this does not seem to be the case for many other HPV types. For example, HPV39 and HPV59 are confined largely to cervical cancers in Central and South America; HPV types 56 and 68 are relatively common elsewhere but not in Central and South America. 6 Further, HPV52 and 58 are rare in North America and Europe, but relatively preva...

HIV-1 and HIV-2 are associated with increased risk for development of HSIL. This risk appears to be associated primarily with increased HPV persistence that may result from immunosuppression related to HIV-1 and/or HIV-2 infection.

Accumulating data indicate that tumor-infiltrating regulatory T cells (Treg) are present in human tumors and locally suppress antitumor immune cells. In this study, we found an increased Treg/CD8 ratio in human breast and cervical cancers. A similar intratumoral lymphocyte pattern was observed in a mouse model for cervical cancer (TC-1 cells).

HIV infection reduces the likelihood of HPV clearance. Among HIV-positive women, immunosuppression, as measured by CD4 cell count, reduces the likelihood of HPV clearance, and HIV type appears to be associated with HPV clearance.

Background:The aim of this study was to examine the potential usefulness of a mammaglobin multigene reverse transcription-PCR (RT-PCR) assay and a mammaglobin sandwich ELISA as diagnostic tools in breast cancer. Methods: We studied peripheral blood samples from 147 untreated Senegalese women with biopsy-confirmed breast cancer and gathered patient information regarding demographic, and clinical staging of disease. The samples were tested for mammaglobin and three breast cancer-associated gene transcripts by a multigene real-time RT-PCR assay and for serum mammaglobin protein by a sandwich ELISA assay. Results: In 77% of the breast cancer blood samples, a positive signal was obtained in the multigene RT-PCR assay detecting mammaglobin and three complementary transcribed genes. Fifty samples from healthy female donors tested negative. Significant correlations were found between mammaglobin protein in serum, presence of mammaglobin mRNA-expressing cells in blood, stage of disease, and tumor size. Circulating mammaglobin protein was detected in 68% of the breast cancer sera, and was increased in 38% in comparison with a mixed control population. The RT-PCR assay and the ELISA for mammaglobin produced a combined sensitivity of 84% and specificity of 97%.