Background
Data on human papillomavirus (HPV) prevalence are essential for developing cost-effective cervical cancer prevention programs.
Methods
In 2005, 710 human immunodeficiency virus (HIV)–positive and 226 HIV-negative Rwandan women enrolled in an observational prospective cohort study. Sociodemographic data, CD4+ cell counts, and cervical specimens were obtained. Cervicovaginal lavage specimens were collected from each woman and tested for >40 HPV types by a polymerase chain reaction assay; HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 were considered primary carcinogenic HPV types.
Results
The prevalence of HPV was higher in HIV-positive women than in HIV-negative women in all age groups. Among HIV-infected women, 69% were positive for ≥1 HPV type, 46% for a carcinogenic HPV type, and 10% for HPV-16. HPV prevalence peaked at 75% in the HIV-positive women aged 25–34 years and then declined with age to 37.5% in those ≥55 years old (Ptrend < .001). A significant trend of higher prevalence of HPV and carcinogenic HPV with lower CD4+ cell counts and increasing cytologic severity was seen among HIV-positive women.
Conclusions
We found a higher prevalence of HPV infection in HIV-positive than in HIV-negative Rwandan women, and the prevalence of HPV and carcinogenic HPV infection decreased with age.
A better understanding of how epidermal growth factor receptor family members (ErbBs) contribute to metastasis is important for evaluating ErbB-directed therapies. Activation of ErbB3/ErbB2 heterodimers can affect both proliferation and motility. We find that increasing ErbB3-dependent signaling in orthotopic injection models of breast cancer can enhance intravasation and lung metastasis with no effect on primary tumor growth or microvessel density. Enhanced metastatic ability due to increased expression of ErbB2 or ErbB3 correlated with stronger chemotaxis and invasion responses to heregulin B1. Suppression of ErbB3 expression reduced both intravasation and metastasis. A human breast cancer tumor tissue microarray showed a significant association between ErbB3 and ErbB2 expression and metastasis independent of tumor size. These results indicate that ErbB3-dependent signaling through ErbB3/ErbB2 heterodimers can contribute to metastasis through enhancing tumor cell invasion and intravasation in vivo and that ErbB-directed therapies may be useful for the inhibition of invasion independent of effects on tumor growth.
The ability of cells to escape apoptosis is critical for carcinogenesis as well as resistance to radiation and chemotherapy. ARC (Apoptosis Repressor with CARD (caspase recruitment domain)) is an unusual inhibitor of apoptosis in that it antagonizes both the extrinsic (death receptor) and intrinsic (mitochondrial/ER) apoptosis pathways. ARC is expressed predominantly in terminally differentiated cells such as cardiac and skeletal myocytes and neurons. Recently, however, the abundance of ARC was noted to be markedly increased in the epithelium of primary human breast cancers compared with benign breast tissue and to confer chemo-and radiation-resistance. Whether the induction of ARC is specific to breast cancer or a more general feature of neoplasia remains unknown. In this study, we assessed the abundance and subcellular localization of ARC in 21 human colon cancer cell lines and in 44 primary human colon adenocarcinomas and adjacent benign colonic tissue. ARC was present at high levels in most colon cancer cell lines and in almost all primary colon cancers compared with corresponding controls. Levels of ARC in the cytoplasm were increased in well, moderately, and poorly differentiated cancers compared with benign tissue, while levels of nuclear ARC were increased only in moderately differentiated tumors. Moreover, epithelial cancers of the ovary and cervix exhibited increased ARC abundance compared with controls. These results demonstrate that ARC is a novel marker of human colon cancer and suggest that it may be a general feature of epithelial cancers.
A Japanese study reported that up to 16% of breast cancer samples harbor a sporadic mutation within the human Cav-1 gene, namely P132L. To date, however, no studies have examined the United States' population. Here, we developed a novel allele-specific real-time PCR assay to detect the Cav-1 P132L mutation in mammary tumor cells isolated by laser capture microdissection from formalin-fixed paraffin-embedded breast cancer samples. We report that the Cav-1 P132L mutation is present in ϳ19% of estrogen receptor ␣ (ER␣)-positive breast cancers but not in ER␣-negative breast cancers. This is the first demonstration that the P132L mutation is exclusively associated with ER␣-positive mammary tumors. We also identified six novel Cav-1 mutations associated with ER␣-positive breast cancers (W128Stop, Y118H, S136R, I141T, Y148H, and Y148S). Thus, the overall incidence of Cav-1 mutations in ER␣-positive breast cancers approaches 35% (greater than one-third). To mechanistically dissect the functional relationship between Cav-1 gene inactivation and ER␣ expression, we isolated primary mammary epithelial cells from wild-type and Cav-1 ؊/؊ mice and cultured them in a three-dimensional system, allowing them to form Multiple independent lines of experimental evidence suggest that Cav-1 functions as a mammary gland tumor suppressor gene.1,2 First, Cav-1 mRNA and protein levels are down-regulated in oncogene-transformed NIH 3T3 cells, in many human and mouse breast cancer cell lines, in primary human mammary gland tumors, and in transgenic breast cancer mouse models.3-6 Conversely, Cav-1 re-expression in breast cancer cell lines inhibits anchorage-dependent growth in soft agar and decreases their invasive potential.5,7 Cav-1 expression also reduces the migratory and invasive potential of MTLn3 cells, a metastatic mammary carcinoma line, by preventing epidermal growth factor (EGF)-induced lamellipodia formation and reducing cell migration.8 Forced expression of Cav-1 in the metastatic 4T1.2 mouse mammary carcinoma cell line also inhibits in vivo growth after orthotopic implantation into the mouse mammary gland. Interestingly, Cav-1 Ϫ/Ϫ mice display several abnormal mammary-gland-specific phenotypes. For example, Cav-
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