{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:27:08Z","timestamp":1772166428529,"version":"3.50.1"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000054","name":"national cancer institute","doi-asserted-by":"publisher","award":["5UH3CA189923-05"],"award-info":[{"award-number":["5UH3CA189923-05"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cervical cancer is the fourth most common cancer in the world, affecting mainly women residing in low- and middle-income countries. Progression from a pre-invasive phase to that of an invasive phase generally takes years and provides a window of opportunity to screen for and treat precancerous lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study is being conducted at four sites in north Karnataka, India. Community sensitization activities have been organized in the study areas to create awareness among stakeholders, including elected representatives, physicians, health care workers, and potential participants. Organized community based as well as hospital-based screening is being conducted using visual inspection with acetic acid (VIA). Screen positive women are referred to respective study hospitals for colposcopy and directed biopsy. Participants with confirmed high-grade cervical dysplasia (high-grade squamous intraepithelial lesions or HSIL) who fit all other eligibility criteria will be recruited to the study and will receive cryotherapy using CryoPop\u00ae, an innovative new cryotherapy device.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>There is a need to develop an inexpensive, simple, and effective cryotherapy device for use by frontline health care providers at locations where screening and timely treatment can be given, accelerating access to cervical cancer prevention services and minimizing loss to follow-up of women with precancerous lesions who need treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      Clinical Trial Registry - India CTRI\/2019\/01\/017289 ClinicalTrials.Gov number\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04154644?term=NCT04154644&amp;draw=2&amp;rank=1\">NCT04154644<\/jats:ext-link>\n                      . Registered on November 6, 2019.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-021-05802-8","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T05:05:44Z","timestamp":1639371944000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Safety and efficacy of the new CryoPop\u00ae cryotherapy device for cervical dysplasia in low- and middle-income countries: study protocol for a multicenter open-label non-inferiority clinical trial with historical controls"],"prefix":"10.1186","volume":"22","author":[{"given":"S.","family":"Yogeshkumar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enriquito","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0743-2888","authenticated-orcid":false,"given":"Edward","family":"Kenyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Mensa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina","family":"Thaler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramalingappa","family":"Antartani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kasturi","family":"Donimath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basavaraj","family":"Patil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santosh","family":"Chikaraddi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shailaja","family":"Bidri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aruna","family":"Biradar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muttappa R.","family":"Gudadinni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laxmikant","family":"Lokare","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gayane","family":"Yenokyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mrutyunjaya B.","family":"Bellad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivaprasad S.","family":"Goudar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Derman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Revankar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hema","family":"Patil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramadevi","family":"Wani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranjit","family":"Kangle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramesh Y.","family":"Chavan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahantesh B.","family":"Nagmoti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yogendra M.","family":"Kabadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purushotham","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunita","family":"Vernekar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surekha","family":"Hipparagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijayalaxmi","family":"Patil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Dalal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"issue":"2","key":"5802_CR1","doi-asserted-by":"publisher","first-page":"e191","DOI":"10.1016\/S2214-109X(19)30482-6","volume":"8","author":"M Arbyn","year":"2020","unstructured":"Arbyn M, Weiderpass E, Bruni L, San Jose S, Saraiya M, Ferlay J. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020;8(2):e191\u2013203. https:\/\/doi.org\/10.1016\/S2214-109X(19)30482-6.","journal-title":"Lancet Glob Health"},{"key":"5802_CR2","doi-asserted-by":"publisher","unstructured":"Moving cancer up the global health agenda. Lancet. 2010;375(9371):2051. https:\/\/doi.org\/10.1016\/S0140-6736(10)60942-7.","DOI":"10.1016\/S0140-6736(10)60942-7"},{"issue":"2","key":"5802_CR3","first-page":"307","volume":"94","author":"G Sawaya","year":"1999","unstructured":"Sawaya G, Grimes D. New technologies in cervical cytology screening: a word of caution. Obstet and Gynecol. 1999;94(2):307\u201310.","journal-title":"Obstet and Gynecol"},{"issue":"6","key":"5802_CR4","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/0091-7435(86)90063-0","volume":"15","author":"Y Van der Graaf","year":"1986","unstructured":"Van der Graaf Y, Klinkhamer PJJM, Vooijs GP. Effect of population screening for cancer of the uterine cervix in Nijmegen, The Netherlands. Prev Med. 1986;15(6):582\u201390. https:\/\/doi.org\/10.1016\/0091-7435(86)90063-0.","journal-title":"Prev Med"},{"issue":"3","key":"5802_CR5","doi-asserted-by":"publisher","first-page":"214","DOI":"10.7326\/0003-4819-113-3-214","volume":"113","author":"DM Eddy","year":"1990","unstructured":"Eddy DM. Screening for cervical cancer. Ann Intern Med. 1990;113(3):214\u201326. https:\/\/doi.org\/10.7326\/0003-4819-113-3-214.","journal-title":"Ann Intern Med"},{"key":"5802_CR6","volume-title":"Global strategy to accelerate the elimination of cervical cancer as a public health problem","author":"World Health Organization","year":"2020","unstructured":"World Health Organization. Global strategy to accelerate the elimination of cervical cancer as a public health problem. Geneva: World Health Organization; 2020."},{"key":"5802_CR7","volume-title":"WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention","author":"World Health Organization","year":"2013","unstructured":"World Health Organization. WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. Geneva: World Health Organization; 2013."},{"key":"5802_CR8","volume-title":"WHO guidelines: use of cryotherapy for cervical intraepithelial neoplasia","author":"World Health Organization","year":"2011","unstructured":"World Health Organization. WHO guidelines: use of cryotherapy for cervical intraepithelial neoplasia. Geneva: World Health Organization; 2011."},{"issue":"32","key":"5802_CR9","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/S0968-8080(08)32415-X","volume":"16","author":"RI Anorlu","year":"2008","unstructured":"Anorlu RI. Cervical cancer: the sub-Saharan African perspective. Reprod Health Matters. 2008;16(32):41\u20139. https:\/\/doi.org\/10.1016\/S0968-8080(08)32415-X.","journal-title":"Reprod Health Matters"},{"key":"5802_CR10","series-title":"Programme for SRH HIV, Research Briefing","volume-title":"Costs of cervical cancer screening in Ghana","author":"W Quentin","year":"2010","unstructured":"Quentin W, Adu-Sarkodie Y. Costs of cervical cancer screening in Ghana. Programme for SRH HIV, Research Briefing: (2010)."},{"key":"5802_CR11","unstructured":"Morton D, Tsu V. (n.d.) Treatment of precancer lesions: overcoming the bottleneck. HPW, the Newsletter on HPV. Accessed 15 Apr 2021 https:\/\/tinyurl.com\/yf57vds9"},{"issue":"2","key":"5802_CR12","first-page":"210","volume":"60","author":"FW Abdul-Karim","year":"1982","unstructured":"Abdul-Karim FW, Fu YS, Reagan JW, Wentz WB. Morphometric study of intraepithelial neoplasia of the uterine cervix. Obstet Gynecol. 1982;60(2):210\u20134.","journal-title":"Obstet Gynecol."},{"issue":"1","key":"5802_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4103\/0300-1652.180561","volume":"57","author":"AC Adepiti","year":"2016","unstructured":"Adepiti AC, Ajenifuja OK, Fadahunsi OO, Osasan SA, Pelemo OE, Loto MO. Comparison of the depth of tissue necrosis between double-freeze and single-freeze nitrous oxide-based cryotherapy. Niger Med J. 2016;57(1):1\u20134. https:\/\/doi.org\/10.4103\/0300-1652.180561.","journal-title":"Niger Med J."},{"issue":"4","key":"5802_CR14","doi-asserted-by":"publisher","first-page":"257","DOI":"10.4103\/0970-9371.126659","volume":"30","author":"K Gupta","year":"2013","unstructured":"Gupta K, Malik NP, Sharma VK, Verma N, Gupta A. Prevalence of cervical dysplasia in western Uttar Pradesh. J Cytol. 2013;30(4):257\u201362. https:\/\/doi.org\/10.4103\/0970-9371.126659.","journal-title":"J Cytol."}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-021-05802-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-021-05802-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-021-05802-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T05:11:08Z","timestamp":1639372268000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-021-05802-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["5802"],"URL":"https:\/\/doi.org\/10.1186\/s13063-021-05802-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-721744\/v1","asserted-by":"object"}]},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"15 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The following Institutional Review Boards or Ethics Committees provided approvals for the study:","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declared no conflict of interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"915"}}