{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:32:06Z","timestamp":1792801926094,"version":"4.5.0"},"update-to":[{"DOI":"10.12688\/aasopenres.12910.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000}},{"DOI":"10.12688\/aasopenres.12910.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000}},{"DOI":"10.12688\/aasopenres.12910.3","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000}},{"DOI":"10.12688\/aasopenres.12910.4","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000}}],"reference-count":49,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kenyatta National Hospital Research and Programs Department","award":["KNH\/R&P\/23C\/34\/22"],"award-info":[{"award-number":["KNH\/R&P\/23C\/34\/22"]}],"id":[{"id":"https:\/\/ror.org\/053sj8m08","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["aasopenresearch.org"],"crossmark-restriction":false},"short-container-title":["AAS Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Cancer in Africa is an emerging health problem. In Kenya it ranks third as a cause of death after infectious and cardiovascular diseases. Nearly 31% of the total cancer burden in sub-Saharan Africa is attributable to infectious agents. Information on cancer burden is scanty in Kenya and this study aimed to provide comprehensive hospital based data to inform policies.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Method:<\/ns4:bold>\n                    A cross-sectional retrospective survey was conducted at Kenyatta National Hospital (KNH) and Moi Teaching and Referral Hospital (MTRH) from January 2008 to December 2012. \u00a0Data was obtained from the patients files and the study was approved by the KNH\/University of Nairobi and MTRH Ethics and Research Committees.\u00a0\u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results<\/ns4:bold>\n                    : In KNH, the top five cancers were: cervical (62, 12.4%), breast (59, 11.8%), colorectal (31, 6.2%), chronic leukemia (27, 5.4%) and stomach cancer (26, 5.2%). Some 154 (30.8%) of these cancers were associated with infectious agents, while an estimated 138 (27.6%) were attributable to infections. Cancers of the cervix (62, 12.4%), stomach (26, 5.2%) and nasopharynx (17, 3.4%) were the commonest infection-associated cancers. In MTRH, the five common types of cancers were Kaposi\u2019s sarcoma (93, 18.6%), breast (77, 15.4%), cervical (41, 8.2%), non-Hodgkin\u2019s lymphoma (37, 7.4%) and colorectal, chronic leukemia and esophageal cancer all with 27 (5.4%). Some 241 (48.2%) of these cancers were associated with infectious agents, while an estimated 222 (44.4%) were attributable to infections. Kaposi\u2019s sarcoma (93, 18.6%), cancer of the cervix (41, 8.2%) and non-Hodgkin\u2019s lymphoma (37, 7.4%) were the commonest infection-associated cancers.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusion:<\/ns4:bold>\n                    Our results suggest that\n                    <ns4:bold\/>\n                    30.8% and 48.2% of the total cancer cases sampled in KNH and MTRH respectively were associated with infectious agents, while 27.6% and 44.4% were attributable to infections in the two hospitals respectively. Reducing the burden of infection-attributable cancers can translate to a reduction of the overall cancer burden.\n                  <\/ns4:p>","DOI":"10.12688\/aasopenres.12910.5","type":"journal-article","created":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T09:25:05Z","timestamp":1573723505000},"page":"25","update-policy":"https:\/\/doi.org\/10.12688\/aasopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Cancer in Kenya: types and infection-attributable. Data from the adult population of two National referral hospitals (2008-2012)"],"prefix":"10.12688","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5356-9247","authenticated-orcid":false,"given":"Lucy Wanjiku","family":"Macharia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9119-3167","authenticated-orcid":false,"given":"Marianne Wanjiru","family":"Mureithi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omu","family":"Anzala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2019,11,14]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"953-966","DOI":"10.1158\/1055-9965.EPI-14-0281","article-title":"Cancer in Africa 2012.","volume":"23","author":"D Parkin","year":"2014","journal-title":"Cancer Epidemiol Biomarkers Prev."},{"key":"ref-2","article-title":"National Cancer Control Strategy 2017 \u2013 2022","year":"2017"},{"key":"ref-3","first-page":"1-441","article-title":"Biological agents. Volume 100 B. A review of human carcinogens.","volume":"100","year":"2012","journal-title":"IARC Monogr Eval Carcinog Risks Hum."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"e609-e616","DOI":"10.1016\/S2214-109X(16)30143-7","article-title":"Global burden of cancers attributable to infections in 2012: a synthetic analysis.","volume":"4","author":"M Plummer","year":"The Authors. Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license; 2016","journal-title":"Lancet Glob Health."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"89-95","DOI":"10.1097\/COH.0000000000000329","article-title":"HIV-associated malignancies in sub-Saharan Africa: progress, challenges, and opportunities.","volume":"12","author":"L Chinula","year":"2017","journal-title":"Curr Opin HIV AIDS."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"S13-26","DOI":"10.1097\/QAI.0000000000000124","article-title":"Prevalence and incidence of HIV infection, trends, and risk factors among persons aged 15-64 years in Kenya: results from a nationally representative study.","volume":"66 Suppl 1","author":"D Kimanga","year":"2014","journal-title":"J Acquir Immune Defic Syndr."},{"key":"ref-7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008621","article-title":"The challenge of AIDS-related malignancies in sub-Saharan Africa","volume":"5","author":"A Sasco","year":"2010","journal-title":"PLoS One."},{"key":"ref-8","article-title":"The 2009 Kenya Population & Housing. Counting our people for the Vision 2030.","volume":"IC","year":"2010","journal-title":"Population Distribution by Age Sex and Administrative Unit."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"e42-e48","DOI":"10.1016\/j.jcpo.2013.06.002","article-title":"AMPATH-Oncology: A model for comprehensive cancer care in sub-Saharan Africa.","volume":"1","author":"R Strother","year":"2013","journal-title":"J Cancer Policy."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"121-6","DOI":"10.4103\/0253-7176.116232","article-title":"How to calculate sample size for different study designs in medical research?","volume":"35","author":"J Charan","year":"2013","journal-title":"Indian J Psychol Med."},{"key":"ref-11","article-title":"Biostatistics: A Foundation for Analysis in the Health Sciences","author":"W Daniel","year":"1999"},{"key":"ref-12","first-page":"14-17","article-title":"Sample size calculation in medical studies.","volume":"6","author":"M Pourhoseingholi","year":"2013","journal-title":"Gastroenterol Hepatol Bed Bench."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"1482-8","DOI":"10.1007\/s12098-012-0763-3","article-title":"Sample size estimation in prevalence studies.","volume":"79","author":"R Arya","year":"2012","journal-title":"Indian J Pediatr."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"3030-3044","DOI":"10.1002\/ijc.21731","article-title":"The global health burden of infection-associated cancers in the year 2002.","volume":"118","author":"D Parkin","year":"2006","journal-title":"Int J Cancer."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"216","DOI":"10.3389\/fonc.2016.00216","article-title":"Burden of Cancers Attributable to Infectious Agents in Nigeria: 2012-2014.","volume":"6","author":"M Odutola","year":"2016","journal-title":"Front Oncol."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13027-016-0098-1","article-title":"Molecular analysis of human Papillomavirus detected among women positive for cervical lesions by visual inspection with acetic acid\/Lugol\u2019s iodine (VIA\/VILI) in Libreville, Gabon.","volume":"11","author":"P Moussavou","year":"2016","journal-title":"Infect Agent Cancer."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"e0146603","DOI":"10.1371\/journal.pone.0146603","article-title":"High Burden of Human Papillomavirus (HPV) Infection among Young Women in KwaZulu-Natal, South Africa","volume":"11","author":"S Ebrahim","year":"2016","journal-title":"PLoS One."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"1389-98","DOI":"10.1002\/ijc.28425","article-title":"Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-Saharan Africa.","volume":"134","author":"L Denny","year":"2014","journal-title":"Int J Cancer."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"12-9","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F","article-title":"Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.","volume":"189","author":"J Walboomers","year":"1999","journal-title":"J Pathol."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"664-70","DOI":"10.1002\/ijc.30716","article-title":"Worldwide burden of cancer attributable to HPV by site, country and HPV type.","volume":"141","author":"C de Martel","year":"2017","journal-title":"Int J Cancer."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1186\/s12879-017-2832-8","article-title":"Prevalence of oncogenic human papillomavirus genotypes in patients diagnosed with anogenital malignancies in Botswana.","volume":"17","author":"P Rantshabeng","year":"2017","journal-title":"BMC Infect Dis."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"758-65","DOI":"10.1097\/IGC.0000000000000111","article-title":"Oncogenic viral prevalence in invasive vulvar cancer specimens from human immunodeficiency virus-positive and -negative women in Botswana.","volume":"24","author":"M Tesfalul","year":"2014","journal-title":"Int J Gynecol Cancer."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"e0197845","DOI":"10.1371\/journal.pone.0197845","article-title":"Unusual and unique distribution of anal high-risk human papillomavirus (HR-HPV) among men who have sex with men living in the Central African Republic","volume":"13","author":"R Mboumba Bouassa","year":"2018","journal-title":"PLoS One."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"358-61","DOI":"10.7196\/samj.7542","article-title":"Prevalence of oral and oropharyngeal human papillomavirus in a sample of South African men: a pilot study.","volume":"104","author":"C Davidson","year":"2014","journal-title":"S Afr Med J."},{"key":"ref-25","first-page":"121-4","article-title":"Human papillomavirus genotypes in a subset of head and neck squamous cell carcinoma.","volume":"33","author":"G Kaba","year":"2014","journal-title":"West Afr J Med."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"65-8","DOI":"10.3892\/ol.2010.207","article-title":"Human papillomavirus infection induces NF-\u03baB activation in cervical cancer: A comparison with penile cancer.","volume":"2","author":"M Senba","year":"2011","journal-title":"Oncol Lett."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"161-4","DOI":"10.4149\/av_2011_02_161","article-title":"Increased prevalence of Kaposi\u0384s sarcoma-associated herpesvirus in the Kaposi\u0384s sarcoma-endemic area of western Kenya in 1981-2000.","volume":"55","author":"M Senba","year":"2011","journal-title":"Acta Virol."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"181","DOI":"10.11604\/pamj.2018.29.181.11847","article-title":"Evidence of EBV infection in lymphomas diagnosed in Lusaka, Zambia.","volume":"29","author":"D Kafita","year":"2018","journal-title":"Pan Afr Med J."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"e26302","DOI":"10.1002\/pbc.26302","article-title":"Hodgkin lymphoma, HIV, and Epstein-Barr virus in Malawi: Longitudinal results from the Kamuzu Central Hospital Lymphoma study.","volume":"64","author":"K Westmoreland","year":"2017","journal-title":"Pediatr Blood Cancer."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"3828-36","DOI":"10.1182\/blood.V87.9.3828.bloodjournal8793828","article-title":"The consistent association between Epstein-Barr virus and Hodgkin's disease in children in Kenya.","volume":"87","author":"M Weinreb","year":"1996","journal-title":"Blood."},{"key":"ref-31","first-page":"166-75","article-title":"Burkitt\u2019s lymphoma in Africa, a review of the epidemiology and etiology.","volume":"7","author":"J Orem","year":"2007","journal-title":"Afr Health Sci."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"211-9","DOI":"10.1002\/hep.20027","article-title":"The Gambia Liver Cancer Study: Infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa.","volume":"39","author":"G Kirk","year":"2004","journal-title":"Hepatology."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"2471-7","DOI":"10.1002\/ijc.31280","article-title":"Fraction and incidence of liver cancer attributable to hepatitis B and C viruses worldwide.","volume":"142","author":"D Maucort-Boulch","year":"2018","journal-title":"Int J Cancer."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"41-46","DOI":"10.4103\/ajmhs.ajmhs_36_17","article-title":"Prevalence and risk factors for helicobacter pylori infection in gastroduodenal diseases in Kano, Nigeria.","volume":"17","author":"A Bello","year":"2018","journal-title":"Afr J Med Health Sci."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1750-9378-1-5","article-title":"Helicobacter pylori and cancer among adults in Uganda.","volume":"1","author":"R Newton","year":"2006","journal-title":"Infect Agent Cancer."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"205-8","DOI":"10.1046\/j.1464-410X.1996.09310.x","article-title":"Bladder cancer in various population groups in the greater Durban area of KwaZulu-Natal, South Africa.","volume":"78","author":"A Groeneveld","year":"1996","journal-title":"Br J Urol."},{"key":"ref-37","first-page":"13-23","article-title":"Frequent occurence of esophageal cancer in young people in Western Kenya.","volume":"34","author":"R Parker","year":"2012","journal-title":"NIH."},{"key":"ref-38","doi-asserted-by":"publisher","first-page":"2053-9","DOI":"10.1002\/ijc.29674","article-title":"Incidence of cancer in Nairobi, Kenya (2004-2008).","volume":"137","author":"A Korir","year":"2015","journal-title":"Int J Cancer."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"69-90","DOI":"10.3322\/caac.20107","article-title":"Global Cancer Statistics: 2011.","volume":"61","author":"A Jemal","year":"2011","journal-title":"CA Cancer J Clin."},{"key":"ref-40","article-title":"Strategic Plan","year":"2010"},{"key":"ref-41","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/503249","article-title":"Esophageal Cancer, the Topmost Cancer at MTRH in the Rift Valley, Kenya, and Its Potential Risk Factors.","volume":"2013","author":"K Patel","year":"2013","journal-title":"ISRN Oncol."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"7-10","DOI":"10.4314\/eamj.v86i1.46921","article-title":"Burden and pattern of cancer in western Kenya.","volume":"86","author":"C Tenge","year":"2009","journal-title":"East Afr Med J."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"2893-2917","DOI":"10.1002\/ijc.25516","article-title":"Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.","volume":"127","author":"J Ferlay","year":"2010","journal-title":"Int J Cancer."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"453-471","DOI":"10.1016\/j.semcancer.2004.06.009","article-title":"Infectious agents and cancer: criteria for a causal relation.","volume":"14","author":"J Pagano","year":"2004","journal-title":"Semin Cancer Biol."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"100-110","DOI":"10.1093\/carcin\/bgp263","article-title":"The global burden of cancer: priorities for prevention.","volume":"31","author":"M Thun","year":"2009","journal-title":"Carcinogenesis."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"28-33","DOI":"10.1016\/j.coviro.2016.08.002","article-title":"Viral-associated malignancies in Africa: are viruses 'infectious traces' or 'dominant drivers'?","volume":"20","author":"R Rochford","year":"2016","journal-title":"Curr Opin Virol."},{"key":"ref-47","first-page":"311-26","article-title":"Epidemiology of gastric cancer.","author":"M Plummer","year":"2004","journal-title":"IARC Sci Publ."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"87-108","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012.","volume":"65","author":"L Torre","year":"2015","journal-title":"CA Cancer J Clin."},{"key":"ref-49","article-title":"Burden of Cancer in Kenya; Types, Infection-Attributable and Trends: A National Referral Hospital Retrospective Survey","author":"L Macharia","year":"2018"}],"container-title":["AAS Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v5\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v5\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v5\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T06:30:14Z","timestamp":1574836214000},"score":1,"resource":{"primary":{"URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,14]]},"references-count":49,"URL":"https:\/\/doi.org\/10.12688\/aasopenres.12910.5","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/aasopenres.14118.r27260","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/aasopenres.14118.r27260","asserted-by":"object"}]},"ISSN":["2515-9321"],"issn-type":[{"value":"2515-9321","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,14]]},"assertion":[{"value":"Indexed","URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v5#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/aasopenres.13980.r26613, Clement A Adebamowo, Michael Odutola, Greenebaum Comprehensive Cancer Center, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA, 01 Oct 2018, version 1, 1 not approved","URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v1#referee-response-26613","order":0,"name":"referee-response-26613","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Lucy Wanjiku Macharia<\/b>; \n<i>Posted: 28 Oct 2018<\/i>; \n<b>Authors\u2019 Response to Reviewers\u2019 Comments:<\/b> &nbsp; \n<b>Journal:<\/b>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; AAS Open Research \n<b>Manuscript #:<\/b> 12910 &nbsp; \n<b>Manuscript Title:<\/b> Burden of cancer in Kenya: types, infection-attributable and trends. A national referral hospital retrospective survey &nbsp; We thank the reviewers for having reviewed our manuscript, for the suggestions and for the positive criticism. We have performed a major revision in the manuscript in agreement with the suggestions. We have applied the PAF\/AF standard formula in estimating the number of cancer cases attributable to infections. Secondly, we have conformed to the third edition of the International Classification of Diseases for Oncology (ICD-O) way of listing the cancers. For cancers like leukemias and lymphomas where the ICD-0-3 topographical code was not clear, we converted the IDC-0-3 morphological code to ICD10 topographical code for clarity. We hope that this new version of the manuscript can be reconsidered to be of an acceptable scientific standard. Kindly find below a point-by-point response to the comments and queries. &nbsp; &nbsp;Sincerely, &nbsp;L.W.M   \n<b>Overall Comment:<\/b> \n<b><i>&nbsp;\u201cThis paper provided information on the prevalence of cancers and the proportion of cancers that were attributable to infections in Kenyatta National Hospital (KNH) and Moi Teaching and Referral Hospital (MTRH), Kenya over a 5 year period from 2008 to 2012. These 2 centers are the oldest and largest national referral hospitals in Kenya. The authors <\/i><\/b>\n<b><i>randomly selected some&nbsp;cancer cases reported at these centers <\/i><\/b>\n<b><i>within the study period and reviewed the charts for cancer types and numbers of cancers attributable to infections. The study reported that 40.0% to 53.2% of cancers that were seen in these referral hospitals were attributable to infections.\u201d<\/i><\/b> &nbsp; \n<b>Response:<\/b> We are thankful to the reviewers for revising our manuscript, for the positive criticism and for the suggestions. We have revised the manuscript text, tables, figures and reference list as described below and in the revised manuscript. We have also updated our results and discussions section together with additional analysis as suggested. &nbsp; \n<b>Main comments<\/b> \n<b>1: Title<\/b> \n<b><i>\u201cIn this paper, <\/i><\/b>\n<b><i>the numbers and proportions of cancers associated with infections were presented and not the proportion of cancers attributable to infections. In<\/i><\/b>\n<b><i> order to obtain the proportion of cancers that were attributable to infections, the author would need to apply the formula for the Population Attributable Fraction (PAF) which was not done in this paper.\u201d<\/i><\/b> &nbsp; \n<b>Response:<\/b> We agree with the reviewers\u2019 concern. We have applied the PAF\/AF standard formula in estimating the number of cancer cases attributable to infections. We are thankful for the suggestion. &nbsp; \n<b>2: Introduction<\/b> \n<b><i>\u201cThe introduction is repetitive and should be edited. Separate paragraphs should be devoted to those infections that are established as causes of cancer while those will weaker associations should be in a separate paragraph.<\/i><\/b>  \n<b><i>The role of HIV infection in cancer etiology, prevalence and incidence in Kenya deserves more discussion than just mentioning HIV in a list of pathogens.&nbsp;<\/i><\/b>  \n<b><i>Previous studies of infection-associated cancers in Kenya, East Africa or Sub-Saharan Africa should be discussed briefly to provide more introductions to the field and establish why this study was necessary and what it hopes to accomplish.\u201d<\/i><\/b> &nbsp; \n<b>Response:<\/b> We are grateful for the insightful suggestions. We have edited the introduction as recommended in the new manuscript.  We have included a new paragraph on HIV prevalence and incidence in Kenya together with its associated cancers.  Previous studies on infection-associated cancers in sub-Saharan Africa have been expounded in details in the data analysis section. &nbsp; &nbsp; \n<b>Comment 3: Methods<\/b> \n<b>3.1 \u201cIt would be more informative to describe the demographic characteristics of the catchment areas, the pattern of healthcare services including other hospitals, and referral systems for the two hospitals included in this study. While these are the biggest hospitals, they may not see the most cancer patients if specialized cancer hospitals are located in the same region or city.\u201d&nbsp;  3.2 \u201cThe rationale, application, and choice of sample size calculation are unclear. This is a retrospective case series. The researchers should analyze all the case records that they can find irrespective of sample size calculation. Further, it is highly unlikely that the prevalence of cancer in adult Kenyan population is 50%.\u201d  3.3 \u201cThe justification for randomly selecting case notes to review is not clear. Rather than statistically estimate the number of files, why not obtain the number of patients seen and the number who have a cancer diagnosis directly from the institutions? If this is not possible, the authors should say so.\u201d  3.4&nbsp; \u201cThe randomization procedure is not clear. The authors state that \u201cthe first record was selected randomly every year\u201d. What is the \u201cfirst record\u201d? Record of the first patient seen in the institution within a specific year? The first record selected from among all the patients\u2019 records for a specific year? If the latter how was the selection done? Were all the records assigned numbers and random number generators used to select records?\u201d  3.5 \u201cDo the authors have an objective assessment of the completeness of the records of these two&nbsp; institutions?\u201d  3.6&nbsp; \u201cWhat is the relationship of the two institutions that refused to grant permission for this study and their locations with the institutions that gave permission for the study? A map showing this information would be informative for international readers\u201d  3.7 \u201cThe&nbsp;analytic methods used in the paper and described in the data analysis section should be described better.&nbsp;.\u201d<\/b> &nbsp; &nbsp; \n<b>Response:<\/b> 3.1. We are thankful to the reviewers for the suggestions. We have included the demographic characteristics of the catchment areas together with the pattern of healthcare services in the study site section of the new manuscript. To clarify the reviewers\u2019 concern, there are 12 health facilities in Kenya that offer cancer services; seven private hospitals, two mission hospitals and three public facilities (KNH, MTRH and Coast Province General Hospital). Because of the affordability of the cancer services, most patients opt for the public facilities resulting in congestion of the facilities and long waiting times of the patients. Patients with private insurance and the government-sponsored scheme, National Health Insurance Fund, are more likely to undergo treatment than those without insurance. &nbsp; &nbsp; 3.2. We have edited the sample size calculation section and included detailed explanations with references in the new manuscript. We do agree with the reviewers\u2019 concern of analyzing all the chart reviews. However, due to cost and time constraints, we were only able to analyze 500 files in each hospital, as this was the minimum necessary sample size needed to achieve the required power of the study. We have also come across an article showing that sampling is also applicable in retrospective chart review studies \n<b>[1]<\/b> but to avoid any misunderstanding\n<b>,<\/b> we have included this as one of the limitations of the study. Regarding the prevalence, we stated in the sample size calculation section that the prevalence of cancer in Kenya was unknown at the time of conducting the study. For a better clarification, a 50% prevalence (p) was used in calculating the sample size since it is known that when d =0.05 and a z=1.96, using a p of 0.5 (50%) yields the highest sample size required for cross-sectional studies \n<b>[2]<\/b>\n<b>.<\/b> A detailed explanation has been included in the new manuscript. &nbsp; 3.3. We thank the reviewers for the positive criticism. For clarification, knowing the number of patients with cancer was not our only objective. We also aimed at knowing the of cancer types, the sex and age of the patients under study, their origin by birth, the method of cancer diagnosis used, year of diagnosis and whether the patient was referred from another health facility. At the time of the study, the hospital databases could not provide all the information needed and therefore we had to use the files. Randomization was done because of the cost and time constraints. In a facility like KNH that had 17,584 cancer files, abstracting all the information needed from the patient files to the data collection form would cost more and need longer time that the time allocated to us by the ethics committee. &nbsp; 3.4. We agree with the reviewer\u2019s concern. We have modified the randomization section.&nbsp; For clarification, the files in KNH were captured in a database and randomization was purely an automated process since all files have a hospital number (that cannot be disclosed to protect the privacy of the patients). However, in MTRH, the records department was in the middle of updating their databases when this study was being done and because of this we were only given an estimate of the number of files and to achieve the required sample size we used convenient sampling method. &nbsp; 3.5. Yes, the authors had an objective assessment of the completeness of the records at the two institutions. First, randomization depended on the total number given to us of the number of cancer files available for the five year period. Secondly, to obtain all the data for the questions we had, we needed to use a patient file with complete information. &nbsp; 3.6. We thank the reviewers for the question. The four hospitals initially selected for the study included; Kenyatta National Hospital (KNH), Moi Teaching and Referral Hospital (MTRH), Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) and Coast General Hospital previously known as Coast Province General Hospital (CPGH). At the time, they were all teaching and referral hospitals. &nbsp;KNH and MTRH are national hospitals&nbsp;(level 6) while JOOTRH and CPGH are level 5 hospitals. KNH is located in the former Nairobi province, MTRH is located in the former Rift Valley province, JOOTRH is located in the former Nyanza province and CPGH is located in the former Coast Province. Although we had ethical approval together with a letter of authority from the Ministry of Health giving us the authorization to conduct research in the four facilities, permission to access the files was only granted by the National hospitals. We have included a map in the new manuscript to guide international readers. We are very grateful for the suggestion. &nbsp; 3.7. We are thankful for the suggestion. We have edited the \u201cdata analysis\u201d section in the new manuscript.  \n<b>Comment 4: Results<\/b> \n<b>\u201cThe authors should be precise in reporting results. \u201cAround 4304 inpatient cancer cases were available in MTRH\u201d is imprecise and unacceptable.\u201d <\/b> &nbsp; \n<b>\u201cThere is a clear difference in the cases of cancer at the KNH compared to MTRH, most probably because one site hosts AMPATH HIV treatment and prevention programs. It is therefore not justifiable to make too much of the differences in the proportion of cancers seen in these two institutions and attempt to extrapolate that to the general population.\u201d<\/b> &nbsp; \n<b>Response:<\/b> We appreciate the suggestion. We have improved the precision of reporting the results. &nbsp; We thank the reviewers for the suggestion. We have edited the results section and minimized extrapolating the differences from the two facilities to the general population. &nbsp; &nbsp; \n<b>Comment 5: Discussion<\/b> \n<b><i>5.1. \u201cThe interpretation of the result is not justifiable based on the data, methods, and analyses.&nbsp;  5.2. Proportions of cancers presenting in specific institutions may not reflect population level epidemiology of the cancers. See Chapter 1 of the Cancer in Africa (Ed) Max Parkin et al.&nbsp;&nbsp;<\/i><\/b>  \n<b><i>5.3. The authors suggest that their data shows the incidence of the cancers that they described but this is not correct.&nbsp;<\/i><\/b>  \n<b><i>5.4. The authors can describe the pattern of cancers presenting to each of these hospitals over a period of time, but this is not \u201cincidence\u201d of those cancers in the population. The pattern of presentation of cancers to specific hospitals is influenced by many factors. An example is illustrated in their paper where the pattern of cancers presenting at the AMPATH related hospital reflects the focus on HIV treatment and prevention at the institution.\u201d<\/i><\/b>  \n<b>Response:<\/b> 5.1. We thank the reviewers for the positive criticism. We have modified the analysis and improved on the interpretation of the data. We have emphasized where necessary that we were comparing our hospital-based results to other results obtained from population-based studies. &nbsp; 5.2. We agree with the reviewer\u2019s concern that the proportions of cancers presenting in specific institutions may not be reflective at a population level. We have highlighted this as a limitation of this study. &nbsp; 5.3. The use of the term \u201cIncidence\u201d was an unintended mistake. We have edited the discussion section and thank the reviewers for the observation. &nbsp; 5.4. We agree with the reviewer\u2019s observation. We have edited our new manuscript accordingly and avoided the use of the term incidence. &nbsp; &nbsp; \n<b>Comment 6: General comments<\/b>  \n<b><i>There are several grammatical and typographical errors in the paper. For example in the Discussion section, Paragraph 3 \u201cElsewhere, a study aiming determine the burden and pattern of cancer in \u2026\u2026.\u201d<\/i><\/b> \n<b><i>There is inconsistency in the format of data presentation. For example, age groups were&nbsp;written as 22 to 44 years and in another 45-65 years and elsewhere 45-64 years.&nbsp;<\/i><\/b> \n<b><i>Some sentences are too long. E.g. &quot;Nearly 15% of the global cancer burden is attributable to infectious agents, with two-thirds of infection attributable cancers occurring in the less developed countries and in which infections accounts for nearly one in four cancers.&quot;<\/i><\/b>  &nbsp; \n<b>Response:<\/b> 6.1. We thank the reviewer for the observation. We have improved on the wording of the manuscript and corrected the typographical errors. 6.2. We thank the reviewer for the comment. We have ensured consistency in the data presented in the new manuscript. 6.3. We thank the reviewer for the suggestion. We have minimized the use of long sentences in the new manuscript. &nbsp; \n<b>Comment 7: Summary<\/b> \n<b><i>\u201cIn this paper, the authors described the prevalence of cancers and the proportion of cancers that were associated with infections in two referral hospitals in Kenya. The data was over-interpreted. The methods are inadequately described and the results are poorly presented. The conclusions drawn from the data are not justifiable.\u201d<\/i><\/b> &nbsp; \n<b>Response:<\/b> We thank the reviewer for the positive criticism. We have performed major revision in the new manuscript taking all suggestions into account. We have applied the standard formula of calculating the cancers attributable to infections. We have updated the methodology section and we have ensured that the results or tables are listed according to the third edition of the International Classification of Diseases for Oncology (ICD-O). We have only reported the results as generated from the data from the two hospitals and highlighted where necessary that we were comparing our hospital-based data with other population-based studies. We have inserted a new paragraph on the limitations of this study and modified the conclusion. We are thankful for the suggestions. &nbsp; \n<b>References<\/b> 1. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Gearing RE, Mian IA, Barber J, Ickowicz A. A methodology for conducting retrospective chart review research in child and adolescent psychiatry. J Can Acad Child Adolesc Psychiatry. 2006;15: 126\u2013134. doi:10.1186\/1478-4505-4-26 2. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Arya R, Antonisamy B, Kumar S. Sample size estimation in prevalence studies. Indian J Pediatr. 2012;79: 1482\u20131488. doi:10.1007\/s12098-012-0763-3","URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v5#referee-comment-3088","order":1,"name":"referee-comment-3088","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/aasopenres.13993.r26698, Maria Paula Curado, Postgraduate Program in Health Sciences, Federal University of Goia\u00b4s, Goi\u00e2nia, Brazil, 31 Dec 2018, version 2, 2 not approved","URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v2#referee-response-26698","order":2,"name":"referee-response-26698","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Lucy Wanjiku Macharia<\/b>; \n<i>Posted: 25 Feb 2019<\/i>; \n<b>&nbsp;Authors\u2019 Response to Reviewers\u2019 Comments:V2<\/b> &nbsp; \n<b>Journal:<\/b>&nbsp;AAS Open Research \n<b>Manuscript #:<\/b> 12910 &nbsp; \n<b>Manuscript Title:<\/b> Cancer in Kenya: types and infection-attributable. Data from two national referral hospitals &nbsp; We thank the reviewer for having reviewed our manuscript, for the suggestions and for the positive criticism. We have revised the manuscript in agreement with the suggestions. The discussion section has been edited to shorten the section. We hope that this new version of the manuscript can be considered for approval. Kindly find below point-by-point response to the comments and queries. &nbsp; Sincerely,  \n<b>Lucy Wanjiku &nbsp;Macharia<\/b>   \n<b><u>Comments<\/u><\/b> \n<b>1: Title<\/b> \n<b><i>\u201cThe title is not clear with the aims\u201d Cancer in Kenya data from two National referral hospitals&quot; It is not possible to have trends as it is a cross sectional study in two hospitals in Kenya.\u201d<\/i><\/b> \n<b>Response:<\/b> We have modified the title to make the aim clear and have removed the \u201ctrends\u201d from the title. We are thankful for the suggestions &nbsp; \n<b>2: Abstract<\/b> \n<b><i>\u201cNo comments\u201d.<\/i><\/b> \n<b>Response:<\/b> We are thankful for the positive feedback &nbsp; \n<b>3: Introduction<\/b> \n<b><i>\u201cNo comments\u201d.<\/i><\/b> \n<b>Response:<\/b> We are grateful for the positive feedback. &nbsp; \n<b>4: Methods<\/b> \n<b>4.1 \u201cWhy were patients aged less than 18 excluded from the study.\u201d&nbsp; 4.2 \u201cWhy was clinical diagnosis not included.\u201d 4.3 \u201cThis type of study has limitations it cannot give more information about the hospital activities. More description about the hospital facilities (number of beds, medical, nurses, etc, radiotherapy etc.\u201d<\/b>  \n<b>Responses:<\/b> We are thankful for the questions. There was no objective exclusion of patients under the age of 18 years. It was mainly to circumvent possible ethical debates revolving the use of data from under age group. All the cases had a clinical diagnosis but for them to be included in the study, a confirmatory diagnosis besides clinical, was prerequisite. We agree with the reviewer\u2019s concern. An improved description of the hospital facilities has been provided in the methodology section of the new manuscript. However, to get the exact information additional permission would need to be sought from the Hospitals. &nbsp; \n<b>5: Results<\/b> \n<b>5.1. \u201c Figure 1 please add the period 2008-2012 sample (500\/500).<\/b> \n<b>5.2. \u201cFigure 2 this is not trends it is a proportion of cases treated in the period, it means that more patients have access to treatment in 2008 to 2011 and less in 2012. I suggest to use a histogram instead of lines for this figure and change the title.<\/b> \n<b>5.3. \u201cWhy were only two cancer sites used?\u201d<\/b> \n<b>5.4. \u201cSame observations for figure 3\u201d<\/b> &nbsp; \n<b>Responses:<\/b> We are thankful for the suggestions. The period 2008-2012 sample (500\/500) has been added in Figure 1. We agree with the reviewer\u2019s concern and have modified Fig. 2 and Fig. 3 into a histogram and changed their titles. We used two cancer sites as they are the only ones who gave permission to access their data among all the four referral hospitals targeted at the time of the study. The reasons for refusal by the other hospitals are unknown. &nbsp; &nbsp; \n<b>6: Discussion<\/b> \n<b>I was expecting a comparison of your data with Eldoret and Nairobi cancer registry. The discussion is long for the data, please make it shorter. ASR are only possible to generate if you have a population based cancer registry database.<\/b> We are grateful for the suggestion. The discussion section has been modified to shorten the section. There are limited published studies on \u201cCancer in Kenya\u201d and the few mentioned were among the few obtainable. Specifically, Reference 37 used the Nairobi Cancer Registry data &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Reference 41 used the Eldoret Cancer Registry data &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Reference 40 The study was done at MTRH&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Reference 39 is a Kenya National cancer control strategy report","URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v5#referee-comment-3102","order":3,"name":"referee-comment-3102","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/aasopenres.14118.r27260, Delphine Casabonne, Unit of Infections and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Barcelona, Spain, 27 Nov 2019, version 5, indexed","URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v5#referee-response-27260","order":4,"name":"referee-response-27260","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/aasopenres.14030.r27129, Kalina Duncan, Center for Global Health, U.S. National\u00a0Cancer\u00a0Institute, Rockville, MD, USA, 30 Aug 2019, version 3, 1 approved, 1 approved with reservations, 2 not approved","URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v3#referee-response-27129","order":5,"name":"referee-response-27129","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Lucy Wanjiku Macharia<\/b>; \n<i>Posted: 03 Oct 2019<\/i>; \n<b>Dear Dr. Kalina Duncan,<\/b> Thank you for reading our manuscript, for the suggestions and the approval status. &nbsp;Kindly find below the response to the queries.  \n<b><u>Comments<\/u><\/b> \n<b>In the methods section: You note there are &quot;few&quot; radiation machines but more may be coming. It would help the context here to report the number and perhaps remove the bit about more coming unless it can be cited in some way? Or if you have provide more specificity about how and where those machines are intended to go, that will be helpful.<\/b> We thank the reviewer for the comment. We have edited the statement, included the number of radiation machines and removed \u201cthe more are coming\u201d bit due to lack of a proper citation. &nbsp; \n<b>Also in Methods: you introduce AMPATH without clarifying what it is. I would recommend providing a sentence of background of their role at MTRH.<\/b> We are thankful for the suggestion. We have included a sentence to connect AMPATH and MTRH. &nbsp; \n<b>In Discussion: At KNH, there is variability in breast cancer proportions that may be interesting to look at. From 2008-2011, the proportion was between 10-15%. In 2012, it drops to below 5%. What happened that year? Were there really fewer cases? Was there an issue with data quality (more incomplete records, etc.)?<\/b> We agree with the reviewer\u2019s concern.&nbsp; The variability from the proportions of the breast cancer at KNH could have been influenced by various factors including the sample size used as compared to sampling the whole frame which was not feasible due to cost constraints. Similarly, maybe there were high numbers of patients with breast cancer that visited the hospital in certain years as compared to others. We have removed the proportion section from the results and discussion in line too with the suggestion from the previous reviewer. We are thankful for the keen observation. &nbsp; \n<b>In Discussion: <\/b>\n<b>You have this line: &quot;The high number of Kaposi's sarcoma, non-Hodgkin's lymphoma and cervical cancer could have been influenced by the association of the cancers with HIV&quot; regarding the high number of HIV-related cases at MTRH. I think this actually requires further discussion, as it pushes the infection-related rates way above average<u>. <\/u>The presence of the AMPATH program, and its specialization in treating patients with HIV should be noted in discussion, as explanation. Because these are hospital-based data, this is especially important to note as this hospital attracts many HIV positive patients, most likely. I would consider an examination and a citation to the article listed below, &quot;Viral-associated malignancies in Africa: are viruses \u2018infectious traces\u2019 or \u2018dominant drivers\u2019?&quot;.<\/b> \n<b>References<\/b> \n<b>1. Rochford R, Korir A, Newton R: Viral-associated malignancies in Africa: are viruses 'infectious traces' or 'dominant drivers'?. <i>Curr Opin Virol<\/i>. 20: 28-33 PubMed <\/b> &nbsp; We thank the reviewer for the suggestion. We have modified the discussion section to incorporate the new suggestions and reference.","URL":"https:\/\/aasopenresearch.org\/articles\/1-25\/v5#referee-comment-3127","order":6,"name":"referee-comment-3127","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study was funded by Kenyatta National Hospital Research and Programs Department [KNH\/R&P\/23C\/34\/22].\n\nLWM is a mentee of the Stem Cell Science and Applications programme of the STEM Learning Initiative, a programme of the African Academy of Sciences\u2019 (AAS) funding body The Alliance for Accelerating Excellence in Science in Africa (AESA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":7,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}