Soluble interleukin 2 receptor levels and cervical neoplasia: results from a population-based case-control study in Costa Rica
Progression from infection with human papillomavirus (HPV) to cervical cancer in some women is thought to involve a permissive host environment, one in which immune response is mobilized in an inappropriate manner. In a previous study (A. Hildesheim et al., Cancer Epidemiol. Biomark. Prev., 6: 807-8...
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creator | Ung, A Kramer, T R Schiffman, M Herrero, R Bratti, M C Burk, R D Swanson, C A Sherman, M E Hutchinson, M L Alfaro, M Morales, J Balmaceda, I Hildesheim, A |
description | Progression from infection with human papillomavirus (HPV) to cervical cancer in some women is thought to involve a permissive host environment, one in which immune response is mobilized in an inappropriate manner. In a previous study (A. Hildesheim et al., Cancer Epidemiol. Biomark. Prev., 6: 807-813, 1997), increasing levels of soluble interleukin 2 receptor (sIL-2R), a known proxy for general immune activation, was found to be positively associated with increasing levels of cervical neoplasia. We attempted to confirm this finding by conducting a nested case-control study of 478 women within a 10,000-woman population-based cohort in Costa Rica. We selected for the study all of the women diagnosed (at enrollment into the cohort) with: (a) low-grade squamous intraepithelial lesions (LSIL, n = 191); (b) high-grade squamous intraepithelial lesions (HSIL, n = 130); or (c) cancer (n = 37). Controls were 120 cytologically normal, HPV-negative women selected from a random sample of the entire cohort. A questionnaire was administered to participants to elicit information on cervical cancer risk factors. All of the women received a pelvic examination during which cervical cells were collected and used for HPV DNA testing by PCR. Blood samples were also collected. Plasma obtained from the blood samples was tested for sIL-2R levels by ELISA. Results indicated that sIL-2R levels increased with age. Among controls, we observed that 44.3% of women over the age of 50 had high levels of sIL-2R (defined as >735 units/ml) compared with 15.8% of women |
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In a previous study (A. Hildesheim et al., Cancer Epidemiol. Biomark. Prev., 6: 807-813, 1997), increasing levels of soluble interleukin 2 receptor (sIL-2R), a known proxy for general immune activation, was found to be positively associated with increasing levels of cervical neoplasia. We attempted to confirm this finding by conducting a nested case-control study of 478 women within a 10,000-woman population-based cohort in Costa Rica. We selected for the study all of the women diagnosed (at enrollment into the cohort) with: (a) low-grade squamous intraepithelial lesions (LSIL, n = 191); (b) high-grade squamous intraepithelial lesions (HSIL, n = 130); or (c) cancer (n = 37). Controls were 120 cytologically normal, HPV-negative women selected from a random sample of the entire cohort. A questionnaire was administered to participants to elicit information on cervical cancer risk factors. All of the women received a pelvic examination during which cervical cells were collected and used for HPV DNA testing by PCR. Blood samples were also collected. Plasma obtained from the blood samples was tested for sIL-2R levels by ELISA. Results indicated that sIL-2R levels increased with age. Among controls, we observed that 44.3% of women over the age of 50 had high levels of sIL-2R (defined as >735 units/ml) compared with 15.8% of women <30 years of age (P = 0.008). When women with cervical disease (LSIL+) were compared with controls, women in the upper quartile of the sIL-2R distribution had an age-adjusted odds ratio (OR) of 2.1 [95% confidence interval (CI), 1.1-4.1]. Comparing each advancing state of neoplasia with its precursor, we found that women with LSIL had higher sIL-2R levels than controls (OR for upper quartile of sIL-2R, 2.3; 95% CI, 1.1-5.2; comparing LSIL cases with controls); women diagnosed with HSIL were similar to the LSIL group (OR for upper quartile of sIL-2R, 1.1; 95% CI, 0.5-2.4; comparing HSIL cases with LSIL cases); and those with cancer had higher sIL-2R levels than subjects with an HSIL diagnosis (OR for upper quartile of sIL-2R = 1.8; 95% CI, 0.5-7.1; comparing cancer cases with HSIL cases). These data suggest that among our study subjects, sIL-2R levels most likely rise as a response to the events of infection and cancerous invasion, but that sIL-2R levels are unlikely to be predictive of disease progression among women with LSIL.</description><identifier>ISSN: 1055-9965</identifier><identifier>PMID: 10090303</identifier><language>eng</language><publisher>United States</publisher><subject>Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Case-Control Studies ; Cervical Intraepithelial Neoplasia - immunology ; Cervical Intraepithelial Neoplasia - virology ; Cohort Studies ; Confidence Intervals ; Costa Rica ; Disease Progression ; DNA, Viral - genetics ; Enzyme-Linked Immunosorbent Assay ; Female ; Forecasting ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Odds Ratio ; Papillomaviridae - genetics ; Papillomaviridae - growth & development ; Papillomavirus Infections - immunology ; Population Surveillance ; Receptors, Interleukin-2 - blood ; Risk Factors ; Surveys and Questionnaires ; Tumor Virus Infections - immunology ; Uterine Cervical Neoplasms - immunology ; Uterine Cervical Neoplasms - virology</subject><ispartof>Cancer epidemiology, biomarkers & prevention, 1999-03, Vol.8 (3), p.249-253</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10090303$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ung, A</creatorcontrib><creatorcontrib>Kramer, T R</creatorcontrib><creatorcontrib>Schiffman, M</creatorcontrib><creatorcontrib>Herrero, R</creatorcontrib><creatorcontrib>Bratti, M C</creatorcontrib><creatorcontrib>Burk, R D</creatorcontrib><creatorcontrib>Swanson, C A</creatorcontrib><creatorcontrib>Sherman, M E</creatorcontrib><creatorcontrib>Hutchinson, M L</creatorcontrib><creatorcontrib>Alfaro, M</creatorcontrib><creatorcontrib>Morales, J</creatorcontrib><creatorcontrib>Balmaceda, I</creatorcontrib><creatorcontrib>Hildesheim, A</creatorcontrib><title>Soluble interleukin 2 receptor levels and cervical neoplasia: results from a population-based case-control study in Costa Rica</title><title>Cancer epidemiology, biomarkers & prevention</title><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><description>Progression from infection with human papillomavirus (HPV) to cervical cancer in some women is thought to involve a permissive host environment, one in which immune response is mobilized in an inappropriate manner. In a previous study (A. Hildesheim et al., Cancer Epidemiol. Biomark. Prev., 6: 807-813, 1997), increasing levels of soluble interleukin 2 receptor (sIL-2R), a known proxy for general immune activation, was found to be positively associated with increasing levels of cervical neoplasia. We attempted to confirm this finding by conducting a nested case-control study of 478 women within a 10,000-woman population-based cohort in Costa Rica. We selected for the study all of the women diagnosed (at enrollment into the cohort) with: (a) low-grade squamous intraepithelial lesions (LSIL, n = 191); (b) high-grade squamous intraepithelial lesions (HSIL, n = 130); or (c) cancer (n = 37). Controls were 120 cytologically normal, HPV-negative women selected from a random sample of the entire cohort. A questionnaire was administered to participants to elicit information on cervical cancer risk factors. All of the women received a pelvic examination during which cervical cells were collected and used for HPV DNA testing by PCR. Blood samples were also collected. Plasma obtained from the blood samples was tested for sIL-2R levels by ELISA. Results indicated that sIL-2R levels increased with age. Among controls, we observed that 44.3% of women over the age of 50 had high levels of sIL-2R (defined as >735 units/ml) compared with 15.8% of women <30 years of age (P = 0.008). When women with cervical disease (LSIL+) were compared with controls, women in the upper quartile of the sIL-2R distribution had an age-adjusted odds ratio (OR) of 2.1 [95% confidence interval (CI), 1.1-4.1]. Comparing each advancing state of neoplasia with its precursor, we found that women with LSIL had higher sIL-2R levels than controls (OR for upper quartile of sIL-2R, 2.3; 95% CI, 1.1-5.2; comparing LSIL cases with controls); women diagnosed with HSIL were similar to the LSIL group (OR for upper quartile of sIL-2R, 1.1; 95% CI, 0.5-2.4; comparing HSIL cases with LSIL cases); and those with cancer had higher sIL-2R levels than subjects with an HSIL diagnosis (OR for upper quartile of sIL-2R = 1.8; 95% CI, 0.5-7.1; comparing cancer cases with HSIL cases). These data suggest that among our study subjects, sIL-2R levels most likely rise as a response to the events of infection and cancerous invasion, but that sIL-2R levels are unlikely to be predictive of disease progression among women with LSIL.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age Factors</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Case-Control Studies</subject><subject>Cervical Intraepithelial Neoplasia - immunology</subject><subject>Cervical Intraepithelial Neoplasia - virology</subject><subject>Cohort Studies</subject><subject>Confidence Intervals</subject><subject>Costa Rica</subject><subject>Disease Progression</subject><subject>DNA, Viral - genetics</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Forecasting</subject><subject>Humans</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness</subject><subject>Odds Ratio</subject><subject>Papillomaviridae - genetics</subject><subject>Papillomaviridae - growth & development</subject><subject>Papillomavirus Infections - immunology</subject><subject>Population Surveillance</subject><subject>Receptors, Interleukin-2 - blood</subject><subject>Risk Factors</subject><subject>Surveys and Questionnaires</subject><subject>Tumor Virus Infections - immunology</subject><subject>Uterine Cervical Neoplasms - immunology</subject><subject>Uterine Cervical Neoplasms - virology</subject><issn>1055-9965</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kMtKBDEQRbNQnHH0FyQrdw1Jp19xJ4MvGBB8rJvqpBqi6U7MY2A2frstjptbm1OnqHtC1pzVdSFlU6_IeYwfjLFW1vUZWXHGJBNMrMn3q7N5sEjNnDBYzJ9mpiUNqNAnF6jFPdpIYdZUYdgbBZbO6LyFaOBm4WK2KdIxuIkC9c5nC8m4uRgg4rKzZKHcnIKzNKasD8shunUxAX1ZZBfkdAQb8fI4N-T9_u5t-1jsnh-etre7wpesTYVmulXIlG61lAOv2lLjOEqOnWh1rbQeOzUq3QBANbB6qAA5aI5C8nJErMSGXP95fXBfGWPqJxMVWgvLMzn2jWxEx_gveHUE8zCh7n0wE4RD_9-Y-AH9MGq3</recordid><startdate>199903</startdate><enddate>199903</enddate><creator>Ung, A</creator><creator>Kramer, T R</creator><creator>Schiffman, M</creator><creator>Herrero, R</creator><creator>Bratti, M C</creator><creator>Burk, R D</creator><creator>Swanson, C A</creator><creator>Sherman, M E</creator><creator>Hutchinson, M L</creator><creator>Alfaro, M</creator><creator>Morales, J</creator><creator>Balmaceda, I</creator><creator>Hildesheim, A</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>199903</creationdate><title>Soluble interleukin 2 receptor levels and cervical neoplasia: results from a population-based case-control study in Costa Rica</title><author>Ung, A ; Kramer, T R ; Schiffman, M ; Herrero, R ; Bratti, M C ; Burk, R D ; Swanson, C A ; Sherman, M E ; Hutchinson, M L ; Alfaro, M ; Morales, J ; Balmaceda, I ; Hildesheim, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p207t-d0d7ce0cd7d99b1472deff91e837d5cddf8cfcd6aaa4b05b4ae1ad1e3912fee43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age Factors</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Case-Control Studies</topic><topic>Cervical Intraepithelial Neoplasia - immunology</topic><topic>Cervical Intraepithelial Neoplasia - virology</topic><topic>Cohort Studies</topic><topic>Confidence Intervals</topic><topic>Costa Rica</topic><topic>Disease Progression</topic><topic>DNA, Viral - genetics</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Forecasting</topic><topic>Humans</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness</topic><topic>Odds Ratio</topic><topic>Papillomaviridae - genetics</topic><topic>Papillomaviridae - growth & development</topic><topic>Papillomavirus Infections - immunology</topic><topic>Population Surveillance</topic><topic>Receptors, Interleukin-2 - blood</topic><topic>Risk Factors</topic><topic>Surveys and Questionnaires</topic><topic>Tumor Virus Infections - immunology</topic><topic>Uterine Cervical Neoplasms - immunology</topic><topic>Uterine Cervical Neoplasms - virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ung, A</creatorcontrib><creatorcontrib>Kramer, T R</creatorcontrib><creatorcontrib>Schiffman, M</creatorcontrib><creatorcontrib>Herrero, R</creatorcontrib><creatorcontrib>Bratti, M C</creatorcontrib><creatorcontrib>Burk, R D</creatorcontrib><creatorcontrib>Swanson, C A</creatorcontrib><creatorcontrib>Sherman, M E</creatorcontrib><creatorcontrib>Hutchinson, M L</creatorcontrib><creatorcontrib>Alfaro, M</creatorcontrib><creatorcontrib>Morales, J</creatorcontrib><creatorcontrib>Balmaceda, I</creatorcontrib><creatorcontrib>Hildesheim, A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer epidemiology, biomarkers & prevention</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ung, A</au><au>Kramer, T R</au><au>Schiffman, M</au><au>Herrero, R</au><au>Bratti, M C</au><au>Burk, R D</au><au>Swanson, C A</au><au>Sherman, M E</au><au>Hutchinson, M L</au><au>Alfaro, M</au><au>Morales, J</au><au>Balmaceda, I</au><au>Hildesheim, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Soluble interleukin 2 receptor levels and cervical neoplasia: results from a population-based case-control study in Costa Rica</atitle><jtitle>Cancer epidemiology, biomarkers & prevention</jtitle><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><date>1999-03</date><risdate>1999</risdate><volume>8</volume><issue>3</issue><spage>249</spage><epage>253</epage><pages>249-253</pages><issn>1055-9965</issn><abstract>Progression from infection with human papillomavirus (HPV) to cervical cancer in some women is thought to involve a permissive host environment, one in which immune response is mobilized in an inappropriate manner. In a previous study (A. Hildesheim et al., Cancer Epidemiol. Biomark. Prev., 6: 807-813, 1997), increasing levels of soluble interleukin 2 receptor (sIL-2R), a known proxy for general immune activation, was found to be positively associated with increasing levels of cervical neoplasia. We attempted to confirm this finding by conducting a nested case-control study of 478 women within a 10,000-woman population-based cohort in Costa Rica. We selected for the study all of the women diagnosed (at enrollment into the cohort) with: (a) low-grade squamous intraepithelial lesions (LSIL, n = 191); (b) high-grade squamous intraepithelial lesions (HSIL, n = 130); or (c) cancer (n = 37). Controls were 120 cytologically normal, HPV-negative women selected from a random sample of the entire cohort. A questionnaire was administered to participants to elicit information on cervical cancer risk factors. All of the women received a pelvic examination during which cervical cells were collected and used for HPV DNA testing by PCR. Blood samples were also collected. Plasma obtained from the blood samples was tested for sIL-2R levels by ELISA. Results indicated that sIL-2R levels increased with age. Among controls, we observed that 44.3% of women over the age of 50 had high levels of sIL-2R (defined as >735 units/ml) compared with 15.8% of women <30 years of age (P = 0.008). When women with cervical disease (LSIL+) were compared with controls, women in the upper quartile of the sIL-2R distribution had an age-adjusted odds ratio (OR) of 2.1 [95% confidence interval (CI), 1.1-4.1]. Comparing each advancing state of neoplasia with its precursor, we found that women with LSIL had higher sIL-2R levels than controls (OR for upper quartile of sIL-2R, 2.3; 95% CI, 1.1-5.2; comparing LSIL cases with controls); women diagnosed with HSIL were similar to the LSIL group (OR for upper quartile of sIL-2R, 1.1; 95% CI, 0.5-2.4; comparing HSIL cases with LSIL cases); and those with cancer had higher sIL-2R levels than subjects with an HSIL diagnosis (OR for upper quartile of sIL-2R = 1.8; 95% CI, 0.5-7.1; comparing cancer cases with HSIL cases). These data suggest that among our study subjects, sIL-2R levels most likely rise as a response to the events of infection and cancerous invasion, but that sIL-2R levels are unlikely to be predictive of disease progression among women with LSIL.</abstract><cop>United States</cop><pmid>10090303</pmid><tpages>5</tpages></addata></record> |
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subjects | Adolescent Adult Age Factors Aged Aged, 80 and over Case-Control Studies Cervical Intraepithelial Neoplasia - immunology Cervical Intraepithelial Neoplasia - virology Cohort Studies Confidence Intervals Costa Rica Disease Progression DNA, Viral - genetics Enzyme-Linked Immunosorbent Assay Female Forecasting Humans Middle Aged Neoplasm Invasiveness Odds Ratio Papillomaviridae - genetics Papillomaviridae - growth & development Papillomavirus Infections - immunology Population Surveillance Receptors, Interleukin-2 - blood Risk Factors Surveys and Questionnaires Tumor Virus Infections - immunology Uterine Cervical Neoplasms - immunology Uterine Cervical Neoplasms - virology |
title | Soluble interleukin 2 receptor levels and cervical neoplasia: results from a population-based case-control study in Costa Rica |
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