Genotyping HPV 16 and 18 in Oral and Oropharyngeal Cancer: Uncovering HIV as a Key Risk Factor in a Ugandan Cohort

Genotyping HPV 16 and 18 in Oral and Oropharyngeal Cancer: Uncovering HIV as a Key Risk Factor in a Ugandan Cohort | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Genotyping HPV 16 and 18 in Oral and Oropharyngeal Cancer: Uncovering HIV as a Key Risk Factor in a Ugandan Cohort Annah Margret Biira, Christopher Kintu, Eriab Nkamba, Adrian Kamulegeya, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5423702/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Sep, 2025 Read the published version in Infectious Agents and Cancer → Version 1 posted 10 You are reading this latest preprint version Abstract Background Human Papillomavirus (HPV) has been associated with oral (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) involving several risk factors in different parts of the world. The aim of this study was to determine the prevalence and factors associated with high-risk HPV 16 and HPV 18 among patients with oral and oropharyngeal squamous cell carcinoma who attended Mulago Hospital, Uganda from 2010–2015. Methods This was a retrospective study in which 174 tissue blocks confirmed with oral and oral pharyngeal squamous cell carcinoma were retrieved from the archives. The corresponding medical charts of the patients were reviewed for demographic and clinical data. Sections of the tissue blocks were reconfirmed for OSCC& OPSCC by staining with H&E. The samples were genotyped for HPV 16, 18 using Multiplex PCR techniques. The data was analyzed using SPSS version 21. Results All 174 samples were confirmed positive for OSCC & OPSCC. HPV DNA was positive in 128 individuals, 46 tested negative. HPV 16 occurred in 55 (32%) subjects and HPV 18 occurred in 37 (21%). Double infection was present in 36 individuals (21%). HIV was the only risk factor significantly associated with HPV 16 associated OSCC& OPSCC (p = 0.018). The overall HPV prevalence was 74%. Conclusions Overall, HPV 16 and 18 are key etiological factors in oral and oral pharyngeal squamous cell carcinoma pathogenesis in the Ugandan population, with a high prevalence. The results suggest that HIV positive individuals are at a higher risk of acquiring HPV 16 associated OPSCC. Alcohol consumption and cigarette smoking are not factors associated with HPV associated OPSCC in this study population. Human Papilloma Virus (HPV) Oral and Oropharyngeal Squamous Cell Carcinoma (OSCC&OPSCC) HIV (Human Immunodeficiency Virus) Figures Figure 1 Figure 2 Background Human papilloma viruses (HPVs) are a heterogeneous group of small non-enveloped DNA viruses that cause an epidemiologically and clinically distinct form of oropharyngeal squamous cell carcinoma (OSCC&OPSCC) [ 1 – 3 ]. More than 100 HPV genotypes have been fully sequenced [ 4 ]. Of the many types, HPV 16 and HPV 18 have consistently been most important epidemiologically and have been associated with squamous cell carcinoma[ 5 ] [ 6 ]. The reports about the factors associated with HPV related OSCC&OPSCC have been conflicting. Some studies report that HPV associated oral and oropharyngeal carcinoma patients show no history of tobacco use and alcohol consumption and thus their disease is routinely attributed to HPV infection [ 5 , 7 , 8 ]. Therefore, importance of HPV in oral squamous cell carcinoma causation is increasing exponentially as reported by some authors [ 9 ]. Fortunately, reports show that HPV associated oral pharyngeal cancers have better prognostic outcomes compared to the cancers from the classical cause [ 10 , 11 ]. The rising trend in HPV prevalence among individuals with OSCC&OPSCC has been attributed to sexual behavior that exposes the oral cavity and pharynx to HPV-16 hence the oral HPV-16-positive tumors [ 12 ]. Oral sex, lifetime number of sexual partners and open-mouth kissing are associated with the development of oral HPV infection and tumors [ 13 , 14 ]. On the other hand tobacco, alcohol use and poor oral hygiene are associated with HPV-16-negative tumors [ 15 ]. As aforementioned, there are several reports on factors associated with HPV-related oral and oral pharyngeal squamous cell carcinoma in different parts of the world. However, studies to clearly identify such associations are still limited in Uganda. Musoke et al (2008) reported high tobacco use and alcohol consumption in Uganda, but the association of these and other factors to HPV related OSCC and OPSCC has not yet been determined. We therefore set out to conduct a study aiming to genotype HPV 16 & 18 in archived specimens from oral and oropharyngeal squamous cell carcinoma cases in a Ugandan population. Methods Ethical consideration The study protocol was approved by the Higher Degree's Research Committee of the Faculty of Medicine, Makerere University. The study also complied with the ethical norms of Mulago Hospital and those of the Ministry of Health of Uganda. A waiver of consent was obtained from the Higher Degree's Research Committee of the Faculty of Medicine, Makerere University before accessing the archive samples used in this study. Sample retrieval We retrieved 174 Formalin Fixed Paraffin Embedded (FFPE) tissue blocks with corresponding medical history from the pathology department, Makerere University, in Kampala. Only those tissue blocks that had histological diagnosis of oral and oropharyngeal squamous cell carcinoma with corresponding medical charts, containing sociodemographic information (2010–2015) were included in the analysis. During retrieval and processing, 20 tissue blocks were disqualified because of inadequacy, alternative diagnosis and one tissue was from the uterus. Other blocks were consecutively retrieved to replace these. Information from the medical charts was retrieved using a data collection form. Each form was assigned a unique identification number representing a FFPE tissue block of a particular case. The information from the medical charts included patient age, sex, alcohol consumption, cigarette smoking, tumor site and HIV status. The retrieved paraffin embedded tissue blocks were re-embedded in fresh paraffin wax and four sections (sandwich method) were cut for testing under strict conditions to avoid potential contamination at the Pathology laboratory. Two sections (the first and the last sections) were stained with Hematoxylin and Eosin (H&E) to confirm diagnosis and to ascertain the suitability of the tissue to continue for HPV genotyping. The sections in-between were collected in a screw-top Eppendorf tube for HPV genotyping. A tissue-free paraffin block was cut after each study block to avoid any HPV carry-over from block to block. A new blade was used for each block and the microtome was cleaned with a vacuum cleaner, Histoclear II and 70% alcohol. To further control for contamination, blank paraffin blocks were simultaneously tested. HPV DNA extraction After confirmation of the blocks on H&E, they were prepared for transportation to the molecular biology lab of Makerere University for DNA extraction and genotyping by PCR. DNA extraction was performed according to manufacturer’s instructions as described elsewhere [16]. Briefly, the residual cells in the preservative medium were centrifuged at 13,000 g for 15 min, and the cell pellets were resuspended in 50 ml of phosphate-buffered saline and centrifuged again at 13,000 g for 15 min. The washed cell pellets were added to a DNA purification column (Generation capture column kit; Gentra Systems, Inc. Minneapolis, MN). The concentration and the quality of the extracted DNA were determined by spectrophotometry. 5μl of DNA solution was used as a template for PCR amplification. HPV genotyping HPV 16 and HPV 18 genotypes were determined as described elsewhere [16]. Briefly, HPV in positive samples was genotyped using multiplex PCR assay targeting the 2 genotypes of high risk HPV. We used 2 sets of genotype-specific primers that could amplify specific regions of both types of high risk- HPV DNA (16 and 18). PCR was performed with a multiplex PCR kit (Qiagen) according to manufactures instruction. Due to possible false negatives that could arise from DNA degradation due to over-fixing, we amplified a fragment of the human β-globin gene using a method and primers described elsewhere[17]. All β-globin-negative samples were excluded from further analysis. Ethical approval for the reported study was obtained from the Higher Degrees Research and Ethics Board (HDREB) of Makerere University College of Health Sciences, Kampala, Uganda. Statistical analysis Based on sample sizes for some categories, we determined the association between categorical variables using Fisher’s Exact test. The t-test was used to determine associations between continuous e.g. age and categorical variables like HPV status. We then modelled the effect of multiple socio-demographic variables on HPV presence using logistic regression. All statistical analyses were performed using R studio package, version R 4.1.2. Results The socio-demographic characteristics of the study participants are shown in Table 1 . A total of 174 archived samples were retrieved: of these, 117 (67%) were from males, and 57 (33%) were from females. The age of the patients ranged from 11 to 84 years mean ± SD, 53.98 ± 15.73 years. Majority (80%) of the subjects were in the age group 31 – 70 years. About 52% of patients were cigarette smokers and 49% were alcohol consumers. According to medical records, 83% of the subjects were HIV negative and only 17% were seropositive. The tumors were described basing on Histological differentiation, Site, and HPV genotype as shown in Table 2 . Well differentiated tumors were observed in 133 (76%) of the subjects, 15 (9%) of the tumors had moderate differentiation and 26 (15%) of the tumors were poorly differentiated. The tongue and mandible were the commonest sites for OPSCC contributing to 78 (45%) and 50 (29%) of all the tumor sites respectively. Each accounted for 3% of the tumor sites. HPV 16 was detected in 55(32%) individuals, HPV 18 and double infections were each detected in 21% of individuals. We found a significant association between HIV sero-positivity and occurrence of HPV 16 associated OPSCC ( Table3 ). However, no association was found between being HIV positive and occurrence of HPV 18 only among subjects confirmed with OPSCC. Likewise, there was no significant association between HIV and having both types of HPV; 16&18 among those confirmed with OPSCC. Similarly, we found no association between the occurrence of HPV and Histological differentiation of the tumor. There was insufficient evidence to suggest a significant relationship between alcohol consumption and HPV occurrence. Surprisingly, HPV genotypes had a higher frequency in non-alcohol consumers as shown in Figure 1 . However, the frequency of HPV 16 was higher in both alcohol consumers and non-alcohol consumers at 26 and 29 subjects respectively compared to other HPV types. Smoking was not associated with occurrence of either HPV genotypes. Finally, HPV was not associated with either smoking or alcohol consumption for either HPV genotypes as shown in the heat map in figure 2 . Discussion In this study, we determined the occurrence and established factors associated with presence of HPV genotypes 16 and 18, among patients diagnosed with oral and/or oropharyngeal squamous cell carcinoma. The overall prevalence of HPV 16 and 18 in oral and oropharyngeal squamous cell carcinoma was 74%. This high prevalence tallies with a previous study from Uganda by Banura et al who reviewed literature from Uganda and reported HPV in Uganda among different subgroups to range from 10–75% [ 18 ]. These studies however did not solely focus on OPSCC. Other studies from the continent; Senegal and Nigeria, for example, reported a low prevalence of HPV associated OPSCC of 3.4% 1.2% respectively [ 19 , 20 ]. Other East African countries like Kenya had either insufficient data on HPV associated prevalence in oral cancer or no data at all. It was therefore hard to make a more geographically associated comparison. This study didn’t find an association between gender and HPV occurrence in OPSCC confirmed subjects. This was true for both single and multiple infections of HPV 16 and 18. This finding is in agreement with most studies about risk factors associated with oral and oropharyngeal Squamous cell carcinomas[ 21 , 22 ]. However, Combes et al and Gillison et al, have reported that HPV associated OPSCC is more common in men than women [ 23 , 24 ]. The age group above 60 had the highest number of cases (40.8%) although it was not statistically significant in comparison to other age groups (P = 0.512). Studies from other continents have reported that HPV-positive patients were significantly younger, more likely to be male and more likely to be white or of other races. Our findings are in agreement with D’Souza et al who found that age does not at all influence the risk of acquiring HPV associated oral and oral pharyngeal squamous cell carcinomas. Whereas the majority of head and neck cancers have been associated with high tobacco and alcohol consumption, patients with OPSCC have been reported by several groups not to have a history of tobacco or alcohol use [ 8 ]. Instead, their tumors are positive for oncogenic HPV types, particularly HPV 16; and their risks are mainly related to sexual history. Our findings are in agreement with these reports as we didn’t find any association between HPV associated OPSCC with alcohol consumption or smoking. Interestingly, HIV was the only risk factor that showed a significant association with HPV-associated OPSCC. Oral HPV prevalence has been associated with HIV-infection and current CD4 cell count in several studies. To the best of our knowledge, this is the first study in Uganda to report an association between any types of HPV associated OPSCC and HIV-1 infection. It has already been established that HIV-infected individuals are at higher risk of developing oropharyngeal cancers [ 25 , 26 ]. This is in agreement with our findings in this study. One explanation for this is the immunocompromised state of HIV-1 infected individuals making them prone to several co-infections. However, with the current roll-out of ART (test and treat policy by WHO), most HIV infected individuals in the country are leaving healthy lives, and for longer. It would be crucial therefore to conduct a more in-depth investigation about this association. The medical charts had missing information about different HIV clinical parameters; for example, we couldn’t identify the CD4 count at the time of diagnosis, neither could we establish ART history of those who were HIV positive. Beachler et al already reported that HIV-infected individuals are living longer due to ART but have a high prevalence of oral HPV infection and have many of the currently determined risk factors for HPV-associated Head and Neck cancers. Also, it will be important for future studies to establish whether the distribution of HPV types in oropharyngeal cancers in HIV‐infected individuals differs from that of the general population. Our study was limited in certain aspects; a relatively small number of HIV positive cases made warrants bigger studies to affirm the association reported here. The duration of fixation was not uniform and could have contributed to a misdiagnosis. Another limitation was inconsistence and gaps in records needed for sociodemographic data collection. We were also not able to genotype other HPV types as part of this study. We recommend future studies to genotype for all other HPV types to determine their respective contributions in oropharyngeal carcinomas. Sexual history couldn’t be established either from the charts and we therefore couldn’t affirm the role of sexual behavior and number of lifetime sex partners in HPV associated OPSCC in the study population. We therefore recommend a higher statistically powered study to clearly establish such associations. Conclusion In this study, we have established the prevalence of HPV associated OPSCC to be 74% in a Ugandan population. We have also reaffirmed the role of HPV in oral and oropharyngeal squamous cell carcinoma etiology in this population. HPV 16 was the majority genotype in the total prevalence of HPV in this population. HIV positive individuals in this Ugandan population are at a higher risk of acquiring oral and oral pharyngeal squamous cell carcinoma associated with HPV 16 and not HPV 18. We report that HPV associated OSCC and OPSCC is not gender dependent and we therefore recommend that the male gender should not be left out in future HPV vaccination in Uganda since they are at a similar risk as females. Abbreviations DNA: Deoxyribonucleic acid; H&E: Haematoxilin and Eosin; HIV: Human Immunodeficiency Virus; HPV: Human papillomavirus; PCR: Polymerase Chain Reaction; OPSCC: oropharyngeal squamous cell carcinoma Declarations Competing interests All authors declare no competing interests in regard to any financial or non-financial relationship. Authors' contributions AMB was responsible for the concept drafting, full proposal development and getting approval from the ethics committees. CK was responsible for the specimen selection and data file cleaning. CK and AMB were responsible for the HPV DNA detection and quality control analysis. AMB and CK wrote the manuscript, and were responsible for the preparation of the manuscript for submission. AMB, MO, CK, EN, and AK Guided data analysis, interpreted data, and edited the paper. MO performed the histopathological evaluation. Acknowledgements We are grateful to Dr. Samuel Kyobe, Mr. Edgar Kigozi, and Mr. Fred Ashaba from the entire Molecular Biology department of Makerere University for their contribution to HPV genotyping and data collection. We thank Dr. Kyityamuwesi Richard for guidance during data collection and interpretation of results. Availability of Data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Funding The study was partially supported by funds from the Ministry of Health, Uganda. The funder had no role in data collection, analysis or interpretation of results. References Applebaum KM, Furniss CS, Zeka A, Posner MR, Smith JF, Bryan J, et al. Lack of association of alcohol and tobacco with HPV16-associated head and neck cancer. J Natl Cancer Inst. 2007;99(23):1801–10. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin oncology: official J Am Soc Clin Oncol. 2011;29(32):4294–301. D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):1944–56. Tommasino M, Alyce A, Debby B, Zigui C, Burk C, Hugo D. Human papillomavirus 33 worldwide genetic variation. J Virol. 2011;448:356–62. Timbang MR, Sim MW, Bewley AF, Farwell DG, Mantravadi A, Moore MG. HPV-related oropharyngeal cancer: a review on burden of the disease and opportunities for prevention and early detection. Hum vaccines immunotherapeutics. 2019;15(7–8):1920–8. Gillison L, Koch M, Capone B, Spafford M, Westra W. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709–20. 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Tables Table 1: Socio-demographic characteristics of the Study Subjects Characteristic Category n (%) Gender Male 117 (67) Female 57 (33) Total 174 (100) Age group 11- 20 years 4 (2) 21- 30 years 9 (5) 31- 40 years 23 (13) 41- 50 years 34 (19) 51- 60 years 41 (24) 61- 70 years 41 (24) 71- 80 years 17 (10) 81- 90 5 (3) Total 174 (100) Cigarette Smoking Smokers 91 (52) Non-smokers 83 (48) Total 174 (100) Alcohol consumption Consumers 86 (49) Non-consumers 88 (51) Total 174 (100) HIV status Positive 30 (17) (17) Negative 144 (83) (83) Total 174 (100) (100) Table 2: HPV type distribution by site and histological differentiation Characteristic Category n (%) Histological Differentiation Poor 26 (15) Moderate 15 (9) Well 133 (76) Total 174 (100) Site Buccal 11 (6) Mandible 50 (29) Maxilla 24 (14) Oral pharynx 5 (3) Palate 6 (3) Tongue 78 (45) Total 174 (100) Type of HPV HPV 16 55 (32) HPV 18 37 (21) HPV 16 AND HPV 18 36 (21) NONE 46 (26) Total 174 (100) Table 3: Association between HPV and HIV HPV P value 16 18 16 & 18 HIV status Positive 6 7 4 0.018 Negative 49 30 32 Alcohol consumption Yes 26 19 18 0.583 No 29 18 21 Cigarette smoking Yes 26 18 22 0.582 No 29 19 14 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 25 Sep, 2025 Read the published version in Infectious Agents and Cancer → Version 1 posted Editorial decision: Revision requested 14 Feb, 2025 Reviews received at journal 11 Feb, 2025 Reviews received at journal 06 Feb, 2025 Reviewers agreed at journal 30 Jan, 2025 Reviewers agreed at journal 28 Jan, 2025 Reviewers agreed at journal 28 Jan, 2025 Reviewers invited by journal 27 Jan, 2025 Editor assigned by journal 11 Nov, 2024 Submission checks completed at journal 11 Nov, 2024 First submitted to journal 09 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5423702","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":376730092,"identity":"f0064a82-6971-4130-8a86-c9bb146dccc6","order_by":0,"name":"Annah Margret 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1","display":"","copyAsset":false,"role":"figure","size":73245,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFrequency of HPV in Alcohol consumers vs Non-alcohol consumers\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5423702/v1/6ef3db1c78c926905e87ffa6.png"},{"id":71624760,"identity":"6dd3d8ba-a126-4717-b741-4894e50e1ed8","added_by":"auto","created_at":"2024-12-17 08:40:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":80390,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHeatmap showing association between HPV genotypes, smoking and alcohol.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5423702/v1/8049891597aae6cd15b5ba8d.png"},{"id":92430499,"identity":"67ca95a7-5f58-4418-874e-34f3bae49d15","added_by":"auto","created_at":"2025-09-29 16:05:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":906342,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5423702/v1/908d5261-96e5-47c0-8db4-7cbfe587a0e5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Genotyping HPV 16 and 18 in Oral and Oropharyngeal Cancer: Uncovering HIV as a Key Risk Factor in a Ugandan Cohort","fulltext":[{"header":"Background","content":"\u003cp\u003eHuman papilloma viruses (HPVs) are a heterogeneous group of small non-enveloped DNA viruses that cause an epidemiologically and clinically distinct form of oropharyngeal squamous cell carcinoma (OSCC\u0026amp;OPSCC) [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. More than 100 HPV genotypes have been fully sequenced [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Of the many types, HPV 16 and HPV 18 have consistently been most important epidemiologically and have been associated with squamous cell carcinoma[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe reports about the factors associated with HPV related OSCC\u0026amp;OPSCC have been conflicting. Some studies report that HPV associated oral and oropharyngeal carcinoma patients show no history of tobacco use and alcohol consumption and thus their disease is routinely attributed to HPV infection [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, importance of HPV in oral squamous cell carcinoma causation is increasing exponentially as reported by some authors [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Fortunately, reports show that HPV associated oral pharyngeal cancers have better prognostic outcomes compared to the cancers from the classical cause [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe rising trend in HPV prevalence among individuals with OSCC\u0026amp;OPSCC has been attributed to sexual behavior that exposes the oral cavity and pharynx to HPV-16 hence the oral HPV-16-positive tumors [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Oral sex, lifetime number of sexual partners and open-mouth kissing are associated with the development of oral HPV infection and tumors [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. On the other hand tobacco, alcohol use and poor oral hygiene are associated with HPV-16-negative tumors [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. As aforementioned, there are several reports on factors associated with HPV-related oral and oral pharyngeal squamous cell carcinoma in different parts of the world.\u003c/p\u003e \u003cp\u003eHowever, studies to clearly identify such associations are still limited in Uganda. Musoke et al (2008) reported high tobacco use and alcohol consumption in Uganda, but the association of these and other factors to HPV related OSCC and OPSCC has not yet been determined. We therefore set out to conduct a study aiming to genotype HPV 16 \u0026amp; 18 in archived specimens from oral and oropharyngeal squamous cell carcinoma cases in a Ugandan population.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eEthical consideration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Higher Degree\u0026apos;s Research Committee of the Faculty of Medicine, Makerere University. The study also complied with the ethical norms of Mulago Hospital and those of the Ministry of Health of Uganda. A waiver of consent was obtained from the Higher Degree\u0026apos;s Research Committee of the Faculty of Medicine, Makerere University before accessing the archive samples used in this study.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample retrieval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrieved 174 Formalin Fixed Paraffin Embedded (FFPE) tissue blocks with corresponding medical history from the pathology department, Makerere University, in Kampala. Only those tissue blocks that had histological diagnosis of oral and oropharyngeal squamous cell carcinoma with corresponding medical charts, containing sociodemographic information (2010\u0026ndash;2015) were included in the analysis. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDuring retrieval and processing, 20 tissue blocks were disqualified because of inadequacy, alternative diagnosis and one tissue was from the uterus. Other blocks were consecutively retrieved to replace these. Information from the medical charts was retrieved using a data collection form. Each form was assigned a unique identification number representing a FFPE tissue block of a particular case. The information from the medical charts included patient age, sex, alcohol consumption, cigarette smoking, tumor site and HIV status.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe retrieved paraffin embedded tissue blocks were re-embedded in fresh paraffin wax and four sections (sandwich method) were cut for testing under strict conditions to avoid potential contamination at the Pathology laboratory. Two sections (the first and the last sections) were stained with Hematoxylin and Eosin (H\u0026amp;E) to confirm diagnosis and to ascertain the suitability of the tissue to continue for HPV genotyping. The sections in-between were collected in a screw-top Eppendorf tube for HPV genotyping. A tissue-free paraffin block was cut after each study block to avoid any HPV carry-over from block to block. A new blade was used for each block and the microtome was cleaned with a vacuum cleaner, Histoclear II and 70% alcohol. To further control for contamination, blank paraffin blocks were simultaneously tested.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHPV DNA extraction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter confirmation of the blocks on H\u0026amp;E, they were prepared for transportation to the molecular biology lab of Makerere University for DNA extraction and genotyping by PCR. DNA extraction was performed according to manufacturer\u0026rsquo;s instructions as described elsewhere [16]. Briefly, the residual cells in the preservative medium were centrifuged at 13,000 g for 15 min, and the cell pellets were resuspended in 50 ml of phosphate-buffered saline and centrifuged again at 13,000 g for 15 min. The washed cell pellets were added to a DNA purification column (Generation capture column kit; Gentra Systems, Inc. Minneapolis, MN). The concentration and the quality of the extracted DNA were determined by spectrophotometry. 5\u0026mu;l of DNA solution was used as a template for PCR amplification.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHPV genotyping\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHPV 16 and HPV 18 genotypes were determined as described elsewhere [16]. Briefly, HPV in positive samples was genotyped using multiplex PCR assay targeting the 2 genotypes of high risk HPV. We used 2 sets of genotype-specific primers that could amplify specific regions of both types of high risk- HPV DNA (16 and 18). PCR was performed with a multiplex PCR kit (Qiagen) according to manufactures instruction. Due to possible false negatives that could arise from DNA degradation due to over-fixing, we amplified a fragment of the human \u0026beta;-globin gene using a method and primers described elsewhere[17]. All \u0026beta;-globin-negative samples were excluded from further analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEthical approval for the reported study was obtained from the Higher Degrees Research and Ethics Board (HDREB) of Makerere University College of Health Sciences, Kampala, Uganda.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBased on sample sizes for some categories, we determined the association between categorical variables using Fisher\u0026rsquo;s Exact test. The t-test was used to determine associations between continuous e.g. age and categorical variables like HPV status. We then modelled the effect of multiple socio-demographic variables on HPV presence using logistic regression. All statistical analyses were performed using R studio package, version R 4.1.2.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe socio-demographic characteristics of the study participants are shown in \u003cstrong\u003eTable 1\u003c/strong\u003e. A total of 174 archived samples were retrieved: of these, 117 (67%) were from males, and 57 (33%) were from females. The age of the patients ranged from 11 to 84 years mean \u0026plusmn; SD, 53.98 \u0026plusmn; 15.73 years. Majority (80%) of the subjects were in the age group 31 \u0026ndash; 70 years. About 52% of patients were cigarette smokers and 49% were alcohol consumers. According to medical records, 83% of the subjects were HIV negative and only 17% were seropositive.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe tumors were described basing on Histological differentiation, Site, and HPV genotype as shown in \u003cstrong\u003eTable 2\u003c/strong\u003e. Well differentiated tumors were observed in 133 (76%) of the subjects, 15 (9%) of the tumors had moderate differentiation and 26 (15%) of the tumors were poorly differentiated. The tongue and mandible were the commonest sites for OPSCC contributing to 78 (45%) and 50 (29%) of all the tumor sites respectively. Each accounted for 3% of the tumor sites. HPV 16 was detected in 55(32%) individuals, HPV 18 and double infections were each detected in 21% of individuals.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe found a significant association between HIV sero-positivity and occurrence of HPV 16 associated OPSCC (\u003cstrong\u003eTable3\u003c/strong\u003e). However, no association was found between being HIV positive and occurrence of HPV 18 only among subjects confirmed with OPSCC. Likewise, there was no significant association between HIV and having both types of HPV; 16\u0026amp;18 among those confirmed with OPSCC. Similarly, we found no association between the occurrence of HPV and Histological differentiation of the tumor. There was insufficient evidence to suggest a significant relationship between alcohol consumption and HPV occurrence. Surprisingly, HPV genotypes had a higher frequency in non-alcohol consumers as shown in \u003cstrong\u003eFigure 1\u003c/strong\u003e. However, the frequency of HPV 16 was higher in both alcohol consumers and non-alcohol consumers at 26 and 29 subjects respectively compared to other HPV types. Smoking was not associated with occurrence of either HPV genotypes. Finally, HPV was not associated with either smoking or alcohol consumption for either HPV genotypes as shown in the heat map in \u003cstrong\u003efigure 2\u003c/strong\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we determined the occurrence and established factors associated with presence of HPV genotypes 16 and 18, among patients diagnosed with oral and/or oropharyngeal squamous cell carcinoma. The overall prevalence of HPV 16 and 18 in oral and oropharyngeal squamous cell carcinoma was 74%.\u003c/p\u003e \u003cp\u003eThis high prevalence tallies with a previous study from Uganda by Banura \u003cem\u003eet al\u003c/em\u003e who reviewed literature from Uganda and reported HPV in Uganda among different subgroups to range from 10\u0026ndash;75% [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These studies however did not solely focus on OPSCC. Other studies from the continent; Senegal and Nigeria, for example, reported a low prevalence of HPV associated OPSCC of 3.4% 1.2% respectively [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Other East African countries like Kenya had either insufficient data on HPV associated prevalence in oral cancer or no data at all. It was therefore hard to make a more geographically associated comparison.\u003c/p\u003e \u003cp\u003eThis study didn\u0026rsquo;t find an association between gender and HPV occurrence in OPSCC confirmed subjects. This was true for both single and multiple infections of HPV 16 and 18. This finding is in agreement with most studies about risk factors associated with oral and oropharyngeal Squamous cell carcinomas[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, Combes et al and Gillison et al, have reported that HPV associated OPSCC is more common in men than women [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The age group above 60 had the highest number of cases (40.8%) although it was not statistically significant in comparison to other age groups (P\u0026thinsp;=\u0026thinsp;0.512). Studies from other continents have reported that HPV-positive patients were significantly younger, more likely to be male and more likely to be white or of other races. Our findings are in agreement with D\u0026rsquo;Souza et al who found that age does not at all influence the risk of acquiring HPV associated oral and oral pharyngeal squamous cell carcinomas.\u003c/p\u003e \u003cp\u003eWhereas the majority of head and neck cancers have been associated with high tobacco and alcohol consumption, patients with OPSCC have been reported by several groups not to have a history of tobacco or alcohol use [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Instead, their tumors are positive for oncogenic HPV types, particularly HPV 16; and their risks are mainly related to sexual history. Our findings are in agreement with these reports as we didn\u0026rsquo;t find any association between HPV associated OPSCC with alcohol consumption or smoking.\u003c/p\u003e \u003cp\u003eInterestingly, HIV was the only risk factor that showed a significant association with HPV-associated OPSCC. Oral HPV prevalence has been associated with HIV-infection and current CD4 cell count in several studies. To the best of our knowledge, this is the first study in Uganda to report an association between any types of HPV associated OPSCC and HIV-1 infection. It has already been established that HIV-infected individuals are at higher risk of developing oropharyngeal cancers [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. This is in agreement with our findings in this study. One explanation for this is the immunocompromised state of HIV-1 infected individuals making them prone to several co-infections. However, with the current roll-out of ART (test and treat policy by WHO), most HIV infected individuals in the country are leaving healthy lives, and for longer. It would be crucial therefore to conduct a more in-depth investigation about this association. The medical charts had missing information about different HIV clinical parameters; for example, we couldn\u0026rsquo;t identify the CD4 count at the time of diagnosis, neither could we establish ART history of those who were HIV positive. Beachler et al already reported that HIV-infected individuals are living longer due to ART but have a high prevalence of oral HPV infection and have many of the currently determined risk factors for HPV-associated Head and Neck cancers. Also, it will be important for future studies to establish whether the distribution of HPV types in oropharyngeal cancers in HIV‐infected individuals differs from that of the general population.\u003c/p\u003e \u003cp\u003e Our study was limited in certain aspects; a relatively small number of HIV positive cases made warrants bigger studies to affirm the association reported here. The duration of fixation was not uniform and could have contributed to a misdiagnosis. Another limitation was inconsistence and gaps in records needed for sociodemographic data collection. We were also not able to genotype other HPV types as part of this study. We recommend future studies to genotype for all other HPV types to determine their respective contributions in oropharyngeal carcinomas. Sexual history couldn\u0026rsquo;t be established either from the charts and we therefore couldn\u0026rsquo;t affirm the role of sexual behavior and number of lifetime sex partners in HPV associated OPSCC in the study population. We therefore recommend a higher statistically powered study to clearly establish such associations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, we have established the prevalence of HPV associated OPSCC to be 74% in a Ugandan population. We have also reaffirmed the role of HPV in oral and oropharyngeal squamous cell carcinoma etiology in this population. HPV 16 was the majority genotype in the total prevalence of HPV in this population. HIV positive individuals in this Ugandan population are at a higher risk of acquiring oral and oral pharyngeal squamous cell carcinoma associated with HPV 16 and not HPV 18. We report that HPV associated OSCC and OPSCC is not gender dependent and we therefore recommend that the male gender should not be left out in future HPV vaccination in Uganda since they are at a similar risk as females.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eDNA: Deoxyribonucleic acid; H\u0026amp;E: Haematoxilin and Eosin; HIV: Human Immunodeficiency Virus; HPV: Human papillomavirus; PCR: Polymerase Chain Reaction; OPSCC: oropharyngeal squamous cell carcinoma\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interests in regard to any financial or non-financial relationship.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAMB was responsible for the concept drafting, full proposal development and getting approval from the ethics committees. CK was responsible for the specimen selection and data file cleaning. CK and AMB were responsible for the HPV DNA detection and quality control analysis. AMB and CK wrote the manuscript, and were responsible for the preparation of the manuscript for submission. AMB, MO, CK, EN, and AK Guided data analysis, interpreted data, and edited the paper. MO performed the histopathological evaluation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to Dr. Samuel Kyobe, Mr. Edgar Kigozi, and Mr. Fred Ashaba from the entire Molecular Biology department of Makerere University for their contribution to HPV genotyping and data collection. We thank Dr. Kyityamuwesi Richard for guidance during data collection and interpretation of results.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was partially supported by funds from the Ministry of Health, Uganda. The funder had no role in data collection, analysis or interpretation of results.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eApplebaum KM, Furniss CS, Zeka A, Posner MR, Smith JF, Bryan J, et al. Lack of association of alcohol and tobacco with HPV16-associated head and neck cancer. J Natl Cancer Inst. 2007;99(23):1801\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin oncology: official J Am Soc Clin Oncol. 2011;29(32):4294\u0026ndash;301.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):1944\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTommasino M, Alyce A, Debby B, Zigui C, Burk C, Hugo D. Human papillomavirus 33 worldwide genetic variation. J Virol. 2011;448:356\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTimbang MR, Sim MW, Bewley AF, Farwell DG, Mantravadi A, Moore MG. HPV-related oropharyngeal cancer: a review on burden of the disease and opportunities for prevention and early detection. Hum vaccines immunotherapeutics. 2019;15(7\u0026ndash;8):1920\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGillison L, Koch M, Capone B, Spafford M, Westra W. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGillison M, Gypsyamber D, Westra W, Sugar E, Weihong X. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008;100:407\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDahlstrom KR, Little JA, Zafereo ME, Lung M, Wei Q, Sturgis EM. 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Annals oncology: official J Eur Soc Med Oncol. 2017;28(12):3065\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcLemore M, Missak H, Smith R, Nuovo G. Head and neck squamous cell carcinomas in HIV-positive patients: a preliminary investigation of viral associations. Head Neck Pathol. 2010;4:97\u0026ndash;105.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNishiwaki M, Yamamoto T, Tone S, Murai T, Ohkawara T, Matsunami T, et al. Genotyping of human papillomaviruses by a novel one-step typing method with multiplex PCR and clinical applications. J Clin Microbiol. 2008;46(4):1161\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eA-M deRodaHusman P, Stel HV, van denBrulel AJC. CJLM Meijer and JMM Walboomers. Processing of long-stored archival cervical smears for human papillomavirus detection by the polymerase chain reaction. Br J Cancer. 1995;72:412\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBanura C, Mirembe FM, Katahoire AR, Namujju PB, Mbonye AK, Wabwire FM. Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review. Infect agents cancer. 2011;6(1):11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNdiaye C, Alemany L, Diop Y, Ndiaye N, Dieme MJ, Tous S, et al. The role of human papillomavirus in head and neck cancer in Senegal. Infect agents cancer. 2013;8(1):14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCathy Ndiaye LA, Yankhoba Diop N, Ndiaye M-J, Di\u0026eacute;m\u0026eacute; S, Tous J, Ellen Klaustermeier MA. Xavier Castellsagu\u0026eacute;, F Xavier Bosch, Helen Trottier and, Sanjos\u0026eacute; Sd. role Hum papillomavirus head neck cancer Senegal. 2013;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChowdary SD, Sekhar PC, Kattapagari KK, Mani Deepthi CH, Neelima D, Reddy BVR. A study to assess expression of human papillomavirus types 16 and 18 in oral squamous cell carcinoma using polymerase chain reaction. J oral maxillofacial pathology: JOMFP. 2018;22(3):347\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAshraf MJ, Hosseini S, Monabati A, Valibeigi B, Khademi B, Abedi E, et al. The Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of Oral Tongue. Iran J Pathol. 2017;12(2):144\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCombes JD, Chen AA, Franceschi S. Prevalence of human papillomavirus in cancer of the oropharynx by gender. Cancer epidemiology, biomarkers \u0026amp; prevention: a publication of the American Association for Cancer Research. cosponsored Am Soc Prev Oncol. 2014;23(12):2954\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGillison ML. Human papillomavirus-related diseases: oropharynx cancers and potential implications for adolescent HPV vaccination. J Adolesc health: official publication Soc Adolesc Med. 2008;43(4 Suppl):S52\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGillison ML. Oropharyngeal cancer: a potential consequence of concomitant HPV and HIV infection. Curr Opin Oncol. 2009;21(5):439\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLekoane KMB, Kuupiel D, Mashamba-Thompson TP, Ginindza TG. The interplay of HIV and human papillomavirus-related cancers in sub-Saharan Africa: scoping review. Syst Rev. 2020;9(1):88.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Socio-demographic characteristics of the Study Subjects\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"389\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 102px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"9\" style=\"width: 102px;\"\u003e\n \u003cp\u003eAge group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e11- 20 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e21- 30 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e31- 40 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e41- 50 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e51- 60 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e61- 70 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e71- 80 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e81- 90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 102px;\"\u003e\n \u003cp\u003eCigarette Smoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eSmokers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNon-smokers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(48)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 102px;\"\u003e\n \u003cp\u003eAlcohol consumption\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eConsumers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(49)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNon-consumers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(51)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 102px;\"\u003e\n \u003cp\u003eHIV status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e30 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e144 (83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e174 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: HPV type distribution by site and histological differentiation\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"408\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 120px;\"\u003e\n \u003cp\u003eHistological Differentiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e26 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e15 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eWell\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e133 (76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e174 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" style=\"width: 120px;\"\u003e\n \u003cp\u003eSite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eBuccal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e11 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eMandible\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e50 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eMaxilla\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e24 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eOral pharynx\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e5 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003ePalate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e6 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eTongue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e78 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e174 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 120px;\"\u003e\n \u003cp\u003eType of HPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eHPV 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e55 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eHPV 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e37 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eHPV 16 AND HPV 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e36 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNONE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e46 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e174 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Association between HPV and HIV\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; HPV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e16\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e16 \u0026amp; 18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHIV status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlcohol consumption\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.583\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCigarette smoking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.582\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"infectious-agents-and-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"iaac","sideBox":"Learn more about [Infectious Agents and Cancer](http://infectagentscancer.biomedcentral.com/)","snPcode":"13027","submissionUrl":"https://submission.nature.com/new-submission/13027/3","title":"Infectious Agents and Cancer","twitterHandle":"@IAC_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Human Papilloma Virus (HPV), Oral and Oropharyngeal Squamous Cell Carcinoma (OSCC\u0026OPSCC), HIV (Human Immunodeficiency Virus)","lastPublishedDoi":"10.21203/rs.3.rs-5423702/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5423702/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eHuman Papillomavirus (HPV) has been associated with oral (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) involving several risk factors in different parts of the world. The aim of this study was to determine the prevalence and factors associated with high-risk HPV 16 and HPV 18 among patients with oral and oropharyngeal squamous cell carcinoma who attended Mulago Hospital, Uganda from 2010\u0026ndash;2015.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis was a retrospective study in which 174 tissue blocks confirmed with oral and oral pharyngeal squamous cell carcinoma were retrieved from the archives. The corresponding medical charts of the patients were reviewed for demographic and clinical data. Sections of the tissue blocks were reconfirmed for OSCC\u0026amp; OPSCC by staining with H\u0026amp;E. The samples were genotyped for HPV 16, 18 using Multiplex PCR techniques. The data was analyzed using SPSS version 21.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAll 174 samples were confirmed positive for OSCC \u0026amp; OPSCC. HPV DNA was positive in 128 individuals, 46 tested negative. HPV 16 occurred in 55 (32%) subjects and HPV 18 occurred in 37 (21%). Double infection was present in 36 individuals (21%). HIV was the only risk factor significantly associated with HPV 16 associated OSCC\u0026amp; OPSCC (p\u0026thinsp;=\u0026thinsp;0.018). The overall HPV prevalence was 74%.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOverall, HPV 16 and 18 are key etiological factors in oral and oral pharyngeal squamous cell carcinoma pathogenesis in the Ugandan population, with a high prevalence. The results suggest that HIV positive individuals are at a higher risk of acquiring HPV 16 associated OPSCC. Alcohol consumption and cigarette smoking are not factors associated with HPV associated OPSCC in this study population.\u003c/p\u003e","manuscriptTitle":"Genotyping HPV 16 and 18 in Oral and Oropharyngeal Cancer: Uncovering HIV as a Key Risk Factor in a Ugandan Cohort","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-17 08:40:50","doi":"10.21203/rs.3.rs-5423702/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-02-14T13:16:39+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-12T02:09:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-06T19:12:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"199589131241027250208698109388186804532","date":"2025-01-30T16:36:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"178348317071217456859584276005600728111","date":"2025-01-28T08:06:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"299793728306043393909552978800273463584","date":"2025-01-28T05:13:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-01-27T18:14:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-11T12:19:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-11T12:18:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Infectious Agents and Cancer","date":"2024-11-09T23:08:34+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"infectious-agents-and-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"iaac","sideBox":"Learn more about [Infectious Agents and Cancer](http://infectagentscancer.biomedcentral.com/)","snPcode":"13027","submissionUrl":"https://submission.nature.com/new-submission/13027/3","title":"Infectious Agents and Cancer","twitterHandle":"@IAC_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"310130cd-1205-4702-96a2-2b26f5c977e4","owner":[],"postedDate":"December 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-29T16:01:26+00:00","versionOfRecord":{"articleIdentity":"rs-5423702","link":"https://doi.org/10.1186/s13027-025-00691-x","journal":{"identity":"infectious-agents-and-cancer","isVorOnly":false,"title":"Infectious Agents and Cancer"},"publishedOn":"2025-09-25 15:57:55","publishedOnDateReadable":"September 25th, 2025"},"versionCreatedAt":"2024-12-17 08:40:50","video":"","vorDoi":"10.1186/s13027-025-00691-x","vorDoiUrl":"https://doi.org/10.1186/s13027-025-00691-x","workflowStages":[]},"version":"v1","identity":"rs-5423702","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5423702","identity":"rs-5423702","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}