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Studies Test Cervical Cancer Prevention in Underserved Populations
Current medical care provides accurate and economical methods for the detection of cervical cancer and effective removal of precancerous cervical lesions. But standard cervical cancer screening and treatment require several clinic visits over the course of many months, an unfeasible approach for women in underserved, limited-resource communities.
A clinical trial reported in the November 2 Journal of the American Medical Association (JAMA) attempted to increase cervical cancer prevention in an underserved population by using a single-visit approach to screening and treatment. Trial participants in California were randomized to either a standard-care or single-visit group. Women in the standard-care group received a conventional Pap test and were immediately discharged home; those with abnormal results were contacted by telephone and urged to return for follow-up. Women in the single-visit group remained in the clinic until their tests were processed, and those with high-grade lesions were offered immediate cervical loop electrosurgical excision. A significantly greater number of women with high-grade lesions in the single-visit group (88 percent) received definitive treatment within 6 months than did women in the standard-care group (53 percent).
A second study reported in the same issue of JAMA tested a noncytology-based screen-and-treat approach in the extremely limited-resource setting of Khayelitsha, South Africa. All participants underwent visual inspection of the cervix with acetic acid (VIA) and human papillomavirus (HPV) DNA testing; 2 to 6 days later, they were randomized to receive treatment based on VIA results, treatment based on HPV DNA results, or delayed evaluation. Women in the VIA and HPV DNA groups with positive test results were immediately offered cryotherapy. Follow-up rates did not differ significantly between groups, but prevalence of high-grade cervical intraepithelial neoplasia and cancer at 6 months were significantly less in both the VIA (2.23 percent) and HPV DNA (0.80 percent) groups compared with the control group (3.55 percent).
In both studies, treatment was offered without definitive diagnosis. But given the very low risk of the interventions and the high likelihood of patients with cervical neoplasia being lost to follow-up, the authors of both studies concluded that these programs are a practical and feasible way to reduce the prevalence of high-grade precancerous cervical lesions in underserved populations.
Study Shows How 1G8 Antibody Inhibits Prostate Cancer
Prostate stem cell antigen (PSCA) is a cell-surface protein found in most prostate cancers, as well as bladder and pancreatic cancer. The level of this antigen's expression correlates directly with prostate cancer severity and inversely with its prognosis. Researchers from UCLA's Jonsson Comprehensive Cancer Center have already shown that an antibody against PSCA - 1G8, which they developed - inhibits tumor growth and metastasis, and improves survival in mice. Now they have characterized the molecular pathways through which the antibody works, publishing their findings in the October 15 Cancer Research.
The team inserted a PSCA expression vector into prostate cancer cells and incubated them in the presence of 1G8. What resulted were weakened plasma membranes, broken nuclei, DNA leakage, and an overall flattened appearance of the cells. However, the cells did not show the usual signs of apoptosis, including chromatin condensation and degradation. When the team tested fragments of the antibody, they found that the full protein and a bivalent (but not monovalent) fragment could induce cell death. Both the bivalent fragment and the full 1G8 antibody slowed tumor growth in mice. The authors concluded that 1G8 acts through a direct antigen cross-linking mechanism that is independent of caspases and of the antibody's cell-attaching Fc domain.
Though these results come from in vitro and mouse studies, they have implications for clinical therapy. "In particular," the authors noted, "knowledge of the mechanism…may affect antibody selection, timing of therapy, therapeutic setting, or rational selection of agents for combination therapy."
Studies Point to Anticancer Potential of Broccoli Sprouts
A chemical in broccoli sprouts may be able to prevent two very different cancers, according to the results of studies presented last week at the American Association for Cancer Research (AACR) "Frontiers in Cancer Prevention Research" meeting. Researchers from Japan reported that people infected with the bacteria H. pylori - which has been associated in several studies with gastric cancer - and who ate the sprouts daily for 2 months had reduced levels of H. pylori and pepsinogen (a biomarker of gastritis), compared with those who ate alfalfa sprouts for the same period.
While they are virtually identical chemically, broccoli sprouts contain high levels of sulforaphane, while alfalfa sprouts contain none. Two months after the study ended, subjects in the broccoli sprout group saw their H.
pylori and pepsinogen levels return to baseline. The researchers attributed the broccoli sprouts' benefit to the protective effect of sulforaphane against cell DNA damage.
To confirm whether the sprouts do indeed have an anticancer effect, the study's leader, Dr. Akinori Yanaka, said during a news conference that his lab hopes to test the intervention over a longer period to see if it can prevent gastric cancer recurrence in those at high risk.
Also at the AACR meeting, researchers from Johns Hopkins University reported that, in a mouse model of UV-light-induced melanoma, sulforaphane extract applied to the skin significantly reduced the risk of cancerous skin tumors. All of the control mice developed cancerous skin tumors, whereas only half of the mice who received a high dose of the extract did. The high-dose mice that developed tumors had their tumor burden reduced by half.
Familial Cancer Risk Estimates Affected by Surveillance Bias
The risk of familial cancer after a parent or sibling is first diagnosed with cancer may be overestimated based on the number of additional cancers found among other family members shortly after the initial diagnosis, according to a study in the November 2 Journal of the National Cancer Institute.
Researchers from the German Cancer Research Centre in Heidelberg followed almost 1.7 million offspring and siblings of 846,448 cancer patients in the Swedish Family Cancer Database. They compared the relative risk of those family members against the general population for developing cancers of the breast, prostate, and cervix, as well as other cancers. For most of the cancers, the relative risk for family members was greatest in the first year but "decreased with time after diagnosis of the first familial tumor," the researchers reported. For example, "daughters of women with breast cancer had a statistically significantly higher relative risk of in situ breast cancer during the year of the mother's diagnosis than they did 5 or more years later," the study found.
The diagnosis of cancer in a family raises concern among the patient's relatives, who may seek medical advice in the immediate aftermath of the initial bad news, resulting in increased detection of asymptomatic tumors - a phenomenon called surveillance bias.
Given the possibility of inflated risk estimates, the scientists cautioned that "the possibility of overestimated familial risks of cancer shortly after diagnosis of the first familial tumor should be considered before a patient's clinical and genetic counseling is implemented."
National Study Shows Relationship of Movies to Kids' Smoking
A new study by researchers at Dartmouth Medical School found that young people who watched the most smoking in the movies were almost three times more likely to start smoking than their peers who watched the least amount of smoking in movies. This result was found throughout all regions of the country, regardless of race and ethnic group. The results of this NCI-funded study were published in the November 7 Journal of Pediatrics.
The researchers surveyed a total of 6,522 adolescents aged 10 to 14 from across the country using a random-digit telephone dial system. The participants were representative of the U.S. population of adolescents in terms of age, sex, household income, and census region. Using a telephone keypad, respondents indicated which movies they had seen out of 50 that had been randomly selected from among the top 532 U.S. box office hits between 1998 and April of 2003 (74 percent of which included smoking).
The study showed that exposure to onscreen smoking was an independent, primary risk factor even after accounting for the impact of other known risk factors for smoking such as parental and sibling smoking, smoking by friends, and rebelliousness, among other factors.
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The report describes the major components of the NCI research portfolio, infrastructure, and resources. It also details five proposed high-impact strategic investments for 2007 and how they will improve patient care and public health. These investments will foster integration within and among NCI-designated Cancer Centers; respond to recommendations for re-engineering cancer clinical trials; link cancer science and technology; advance and support medical informatics and health information systems; and integrate the disciplines and cultures in cancer science. The FY 2007 budget request comprises the increase required to maintain the present level of operations or "current services," plus the increases required for the five new strategic investments.