Human papillomavirus type-specific distribution in cervical intraepithelial neoplasia and cancer in The Gambia prior to HPV immunization programme: A baseline for monitoring the quadrivalent vaccine

Human papillomavirus type-specific distribution in cervical intraepithelial neoplasia and cancer in The Gambia prior to HPV immunization programme: A baseline for monitoring the quadrivalent vaccine | 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 Human papillomavirus type-specific distribution in cervical intraepithelial neoplasia and cancer in The Gambia prior to HPV immunization programme: A baseline for monitoring the quadrivalent vaccine Haddy Bah, Foday Ceesay, Ousman Leigh, Haddy Tunkara Bah, Ahmad Tejan Savage, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4289490/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Sep, 2024 Read the published version in Infectious Agents and Cancer → Version 1 posted 7 You are reading this latest preprint version Abstract Background: Persistent infection with the high-risk human papillomavirus (HR-HPV) is associated with causing nearly 95% of cervical cancer and remains a worldwide concern. In the Gambia, cervical cancer is the leading cause of cancer deaths in women. Current estimates indicate that 286 women are annually diagnosed with cervical cancer with a fatality rate of 70%. In an attempt to address this, in 2019 the quadrivalent HPV vaccine was incorporated into the Gambia’s expanded programme on Immunisation. The aim of the study was to retrospectively assess the prevalence and distribution of high-risk HPV genotype in archived, formalin fixed paraffin embedded cervical biopsy tissues diagnosed with cervical cancer in the Gambia from year 2013 -2022. Method: A total of 223 samples with histologically diagnosis of cervical cancer with adequate tissues were sectioned and deparaffinised, followed by HPV DNA extraction and the detection of HR-HPV by real-time multiplex PCR. The internal housekeeping gene was amplified in 119 samples, which were subsequently tested for HPV DNA. Results: HPV prevalence was found to be 87% (104 /119) in cervical cancer cases, 15 (12.6%) samples tested negative for HPV DNA. In single infections, HPV 16 genotype was the most frequent type in cervical cancer cases accounting for 53% (56/104), followed by other high risk HPV genotypes 17% (18/104), and HPV genotype 18 was found in 15% (16/104) of cervical cancer cases. HPV related cervical cancer was most common in the 32 -42 year (28.8%, 30/104) aged women. A significant association between age and diagnosis with cervical cancer (p = 0.023), and HPV genotype (p = 0.038) was observed. Conclusion: There was no difference in the distribution of HPV 16 and 18 genotypes in cervical cancer cases in The Gambia in comparison with the global distribution. However, the high prevalence of single infections with other HR-HPV, and multiple infections with HPV 16 and other HR-HPV genotypes seen in this study, clearly shows that the nonavalent HPV vaccine could be more beneficial for The Gambia. This study provides The Gambia with a baseline data to use in policy decisions regarding future evaluation of the quadrivalent HPV vaccine in the country. HPV genotype human papilloma virus Cervical cancer HPV vaccines Squamous carcinoma Figures Figure 1 Figure 2 Background Globally, cervical cancer is the fourth most common cancer among women with over 604,000 new cases and approximately 340,000 deaths reported in 2020 [ 1 ]. However, in developing countries, cervical cancer accounts for more than 85% of the global cervical cancer deaths [ 1 ]. The high cases of cervical cancer observed in developing countries may be attributed to low awareness and limited resources to successfully implement nationwide screening programs. Furthermore, the global mortality rate reported from cervical cancer is almost 10 times greater in the developing countries than in developed countries. This is mainly due to late presentation combined with inadequate access to cancer chemotherapy [ 2 ]. In the Gambia, cervical cancer ranks as the most frequent cancer among reproductive aged women 15–44 years with an age standardised incidence rate of 42.9 and age standardised mortality rate of 33.9 per 100,000, respectively [ 3 ]. Current estimates indicate that every year 286 women in the Gambia are diagnosed with cervical cancer and approximately 70% die from the disease. Persistent infection with high-risk human papillomavirus (HR-HPV) genotypes has been identified as the cause for the development of approximately 90% of cervical cancer cases. There are at least 15 HR-HPV genotypes that are known to be associated with cervical cancer, namely: HPV 16,18, 31,33,35,39,45,51,52,53,56,58,59,66 and 68 [ 4 ]. In an attempt to reduce the burden of HPV infection, three recombinant HPV prophylactic vaccines have been developed: a bivalent vaccine that targets HR-HPV genotypes16, 18, a quadrivalent vaccine against HR-HPV 16, 18 and low risk (LR) HPV 6 and 11, and Gardasil 9, which targets 7 HR-HPV genotypes 16, 18, 31, 33, 45, 52, 58 and LR-HPV, 6 and 11. HPV16 and HPV18 genotypes have the strongest association with cervical cancer with international studies reporting their presence in around 70% of cervical cancers [ 5 ]. However, the distribution of other HR-HPV genotypes among cervical cancers across continents and even within Africa has been reported [ 6 , 7 ]. The Gambia is a small country situated in West Africa with a population size of less than 2.5 million; it is divided into namely: Banjul, the capital city, kanifing Municipal, Western, Lower River, North Bank, Central River, and Upper River Regions. Both Kanifing Municipal and Western Region are closer to the capital city, Banjul. The quadrivalent HPV vaccine was introduced in the Gambia in 2019 targeting girls aged 9–14 years residing in the Kanifing Municipality and the Western Region. A vaccine coverage of 83% was achieved for the first dose. However, in 2021, the second dose coverage was about 30%. Although, there is data on the distribution of circulating HPV genotypes in the Gambia [ 8 , 9 ], this is the first baseline study characterising HPV genotypes in archived formalin fixed paraffin embedded (FFPE) biopsy cervical cancer tissues. The primary objectives of this study were to retrospectively assess the prevalence of HPV in archived FFPE cervical biopsy tissues with cervical cancer and to determine if there is any difference in the distribution of HR-HPV 16 and 18 genotypes in cervical cancerous cases in the Gambia comparison with the global distribution. Method Sample selection and collection . The Edward Francis Small Teaching Hospital (EFSTH) is the only tertiary referral hospital for patients or specimens with any form of suspected cancer in The Gambia. The Pathology department maintains a register where all received and processed tissue samples are recorded. This register was used to select paraffin-embedded formalin-fixed cervical tissues of women who were referred to the Pathology unit, Banjul, between January 2013 and December 2022 and diagnosed histologically with high grade precursor lesion (CIN III, high grade squamous Intraepithelial lesion (HSIL), or carcinoma in situ) or cervical cancer (adenocarcinoma, adenosquamous carcinoma or any form of squamous cell carcinoma) for this study. Formalin fixed paraffin embedded (FFPE) tissue blocks that are attached to the cassette, properly stored, and have all the relevant clinical data were selected for processing. Haematoxylin Eosin (H &E) stained slides of these paraffin blocks were examined for cancerous tissues and verified by the department Pathologist. All archived Atypical Squamous Cells of Undetermined Significance (ASCUS), CIN1/2 samples, inadequate tissue material and those with missing clinical data were excluded from processing. Tissue Sectioning A total of 338 FFPE tissue samples with either HGSIL or cervical cancer were retrieved from the pathology department. A hundred and fifteen (115) of these samples had a small number of embedded tissues and were difficult to section. A total of two hundred and twenty-three (223) samples were adequate for sectioning (Fig. 1 ). To avoid cross-contamination from other specimens, the microtome stage and forceps were cleaned with xylene followed by ethanol, and a fresh blade and a new container of water for floating sections was used for each paraffin block. Sixty (60µ) micro of tissue samples were sectioned from each paraffin block. Figure 1 : Sample sectioning and human papillomavirus (HPV) testing for archived FFPE tissue blocks, received from Department of Laboratory Medicine, Histology unit, EFSTH. HPV DNA extraction Nucleic acid was extracted from the FFPE tissue samples using the AmpFire HPV kit (Atila Biosystems). The extraction process consists of lysing of the 60 µ tissue samples with solution A (Catalog number PRMVR − 10) and a lysis buffer. Briefly, the tubes were vortexed for 10 seconds, followed by a brief spin to bring down all the liquid at the bottom of the tube. The tubes were incubated in a 95 O C dry heat block for 1hr 30 minutes with a brief spin after the first 45 mins of incubation. After the incubation, the tubes were allowed to cool down at room temperature, vortexed and briefly spun. The supernatant containing the purified nucleic acid was transferred into microtubes for HPV detection and genotyping. To quality control the extraction process, molecular grade water was used as an internal control. HPV detection and genotyping HPV detection was carried out using AmpFire HPV 16/18/HR assay (Atila Biosystems, Line gene 9200). The test kit is designed for molecular diagnostic in vitro detection and typing of 15 high-risk human papillomaviruses (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) from DNA preparations. It allows simultaneous identification of HPV 16 and 18 and grouped the rest of the HR-HPV (31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) as other HR-HPV. The test system is based on detection of the viral genomic DNA including the viral oncogenes E6/E7 using high-risk HPV specific primers and fluorescent probes under isothermal condition. The Atila Biosystem software evaluates all amplification signals and generates the test results. An additional primer system that amplifies a region of the HPV genomic DNA is integrated into the test system. This serves as a positive control for the DNA preparation. Both positive and negative test controls were included in each run. In addition to the test controls, a molecular grade water was run alongside the controls as an in-house negative control. Samples that failed to amplify the internal housekeeping gene were classified as inadequate or invalid test result. All inadequate and HPV negative samples were rescreened using a new sectioned tissue. Statistical Analysis Epidemiological data was stored using Epi-Info version 7 ( https://www.cdc.gov/epiinfo ) software and was linked to both the clinical data and the HPV genotyping results. The final data base was analysed using IBM SPSS version 21.0. Analysis was primarily descriptive with proportions of each HPV type detected in the cancers. Fisher’s exact test was used to determine the primary outcomes of interest at a p-value of < 0.05 and 95% confidence intervals (CI) were considered statistically significant. Fisher’s test was used to find any relation between HPV types and degree of cytopathologic abnormalities. Results The mean age of women that samples were collected from was 50.4 years (standard deviation, SD ± 12.6, range 13–85). Out of the 338 participants, 326 (96.4%) of them were diagnosed with cervical cancer; 300 (92%) of these cancers were squamous cell carcinoma, 14 (4.3%) adenocarcinoma, 11 (3.4%) carcinoma in-situ and 1 (0.3%) with CIN III with high degree of invasive suspicious of invasive carcinoma. Of the 119 samples that were adequate for HPV DNA screening, 104 were HPV positive and 15 were HPV negative, thus giving HPV positivity rate of 87% (104/119). In single infection, HPV 16 accounts for 53% (56/104) of the HPV genotypes found in the cervical tissues, HPV 18 accounts for 15.4% (16/104), and other HR-HPV17.3% (18/104) (Table 1). Furthermore, HPV 16 and 18 genotypes combined accounts for 69.2% of the cervical cancer cases. In multiple infections, double infections were observed in 14 cases with a prevalence rate as follows: HPV genotype 16 /18 (3.8%, 4/104), HPV genotype 16 and other HR-HPV (6.7%, 8/104), HPV 18 and other HR-HPV (1.9%, 2/104). A majority 93% (97/104) of cervical samples diagnosed with squamous cell carcinoma were HPV positive with HPV genotype 16 being more prevalent (54.6%, 53/97), followed by others - HR-HPV (18.6%, 18/97), and HPV 18 accounting for 14.4%, (14/97) of the squamous cell carcinoma cases, respectively. Table 1: HPV Genotypes Distribution in Cervical Cancer identified by Histotype and Patient Age HPV distribution amongst the different age groups showed HPV 16 related cancer was more prevalent in the 43 − 53-year-old (18.3%), followed by 32–42 aged group (14.4%) (Table 2). The results also showed that 39% of the cervical cancer biopsies that were HPV positive were from the Mandinka ethnicity, followed by the Jola (20%) (Fig. 2 ). The distribution of HPV related cervical cancer in the different regions of the country showed that approximately 52% and 32% of cases were from the West Coast Region (WCR) and Kanifing Municipal Council (KMC) of the country, respectively. Fewer cases of HPV related cervical cancer were observed for the other regions and only 2% of HPV related cervical cancer cases were from the capital city, Banjul. Figure 2 : A graph showing HPV prevalence amongst different ethnicities diagnosed with cervical cancer, Gambia . A bivariate analysis showed there was a significant association between participants’ age with their diagnosis with cervical cancer (p = 0.023) and HPV genotype (p = 0.038) (Table 2). However, no significant association between ethnicity, residential area of the participants and their diagnosis with cervical cancer, HPV result and HPV genotype (p > 0.05) were observed. The participants within the ages 43–53 years had the highest frequency (n = 100, 29.6) of cervical cancer diagnosis and with HPV Genotype 16 (n = 19, 18.3%) as the most prevalent type. Fewer HPV positive cervical cancers were observed in the older age group (76–86 years) (Table 2). Table 2: Association between Age, HPV Genotype and Cervical Cancer Discussion Persistent infection with high -risk HPV genotypes has been identified as the most important aetiologic agent in the pathogenesis of cervical cancer [ 10 ]. Although, geographical variations in the prevalence of HPV DNA in cervical cancer biopsies, has been reported worldwide, the overall prevalence has been reported to be approximately 95% [ 11 , 12 ]. In this cross-sectional study of women diagnosed with cervical cancer from 2013–2022, HPV prevalence was found to be 87% in the analysed cervical cancer tissues with HPV 16 genotype being the most frequent type detected (53.8%), followed by other HR-HPV genotype (17.3%), and HPV 18 genotype accounting for (15.4%) (Table 1). In addition, the combined prevalence of HPV 16 and 18 genotypes accounts for approximately 70% of the cervical cancer cases diagnosed in this study. However, a low HPV 16 carriage rate was observed in cervical swabs from reproductive aged women from Bah Camara et al (2018) study [ 8 ]. Their study identified other HR-HPV genotypes as the most common circulating type in urban Gambia. The high HPV prevalence rate of 87% found in this study is similar to other studies conducted in the neighbouring country, Senegal (90%, and in Nigeria (90.7%) [ 13 , 14 ]. In addition, HPV studies carried out on FFPE samples in Malawi and South Africa also reported a high prevalence rate of 97% and 92%, respectively [ 15 , 16 ]. However, countries including Poland and Iran reported a lower HPV prevalence rate in cervical cancer [ 17 , 18 ]. These differences in HPV prevalence in cervical cancer could be attributed to several factors which may include geographical variations, quality and quantity of samples, sensitivity and specificity of the methods used for DNA extraction and HPV detection [ 19 , 20 ]. The high prevalence (53%) of HPV16 reported in this FFPE study was consistent with other studies, as this genotype is the most prevalence type reported, globally [ 21 , 22 , 23 , 24 ]. Epidemiological, clinical, and molecular studies have shown that HPV 16 and HPV18 genotypes are combinedly responsible for almost 70% of cervical cancers [ 25 , 26 ]. The combined prevalence rate (approximately 70%) of HPV 16 (53.8%) and HPV 18 (15.4%) genotypes reported in this retrospective cross-sectional study corresponds to the estimate of the global distribution of these genotypes responsible for causing cervical cancers, worldwide. They are the most prevalent and most potent carcinogenic viruses, and their probability of disease progression and persistence is significantly higher than other high risk HPV genotypes [ 27 ]. Furthermore, in the 97 tissues diagnosed with squamous carcinoma, HPV 16 genotype accounts for 54.6% (53/97) (Table 1). This result agrees with that of Wall et al., carried out in the Gambia [ 9 ] and Missaoui et al., carried out in Tunisia, North Africa [ 28 ]. Both studies found that HPV 16 is the most frequent genotype among invasive squamous cell carcinomas. However, some studies have reported that other HR-HPV genotypes other than HPV 16 are most common HPV type detected in cervical cancer [ 29 , 30 ]. A study carried out in Parakou, Benin Republic, reported that HPV 16 genotype was not detected in any of the cervical cancer cases, and HPV 39 was the most common genotype detected in their study [ 30 ]. This could be due to geographical variation and /or genotype specific replacement as 15% of cervical cancers are reported to be caused by other HR-HPV [ 31 ] An observation in this study was the high proportion (17.3%) of single infections with other HR-HPV and (6.7%) combined infections of HPV 16 with other HR-HPV genotypes found in the cervical cancer tissue samples. This finding agrees with the result from Bah Camara et al., study that found other HR-HPV genotypes in cervical samples of HIV positive women diagnosed with cervical cancer in The Gambia [ 32 ]. Other studies have also shown that apart from HPV 16 and 18 genotypes, other HR-HPV genotypes that the quadrivalent HPV vaccine does not offer protection against causes cervical cancers [ 31 ]. Although, the Gambia is currently administering the quadrivalent vaccine which targets HPV genotypes 6, 11, 16 and 18, there is a need to switch to the nonavalent HPV vaccine which targets an additional 5 other HR-HPV genotypes (HPV 31, 33, 45, 52, and 58) which are associated of causing 15% of cervical cancers, globally [ 31 ]. HPV DNA negative results was found in 12.6% (15/119) histologically diagnosed cervical cancer cases. This could be due to the rare cases of non-HPV related cervical cancer or integration of the viral genome into the host chromosome, which could lead to changes in the genes the PCR primers target. Of the 326 cervical cancer cases histologically diagnosed in The Gambia, cervical cancer was most common in 43–53-year aged women (29.6%, 100/326). However, HPV related cervical cancer was more prevalent in the 32–42 year (28.8%, 30/104), followed by 43–53 year (27.9%, 29/104) aged women. This finding further shows that women that are mostly affected with cervical cancer in the Gambia are in their mid-adult lives (32–53 years) and possibly having young families. A significant association was found between cervical cancer diagnosis and age (P < 0.05) and HPV genotype (p < 0.05) (Table 2). The high (39%) HPV related cervical cancer observed in the Mandinka ethnic is not surprising as it is the most predominate ethnicity of the country. However, no significance association was found between HPV genotype, cervical cancer diagnoses and ethnicity. Another interesting finding from this study was that less histologically diagnosed cervical cancer cases was observed for the Northern, Central, and Upper Regions of the country compared to the Western (52%) and (32%) Kanifing Municipal Regions. These differences could be attributed to several factors among which include access, and proximity of the only histology department in the country, which is situated at the teaching hospital in Banjul, the capital city. The low (2%) prevalence rate of histologically diagnosed cervical cancer observed in the capital city could also be attributable to residents having access to early cervical cancer screening and pre cancer management, which is also offered in the teaching hospital in Banjul. This highlight the need to decentralise cervical cancer screening in the country for easy access and management of precancerous lesions, and prompt treatment options. Conclusion This study showed that the overall frequency of HPV genotypes detected in women with cervical cancer in The Gambia was high. HPV 16, other HR-HPV, and HPV 18 genotypes were the most prevalence types found causing cervical cancer in a single infection. HPV 16 and other HR-HPV were the most common genotypes in multiple infections. In view of these results, the use of the Gardasil-9® (nonavalent) vaccine could provide a more effective cervical cancer prevention in The Gambia. Furthermore, monitoring the changes in HPV genotype distribution will allow ongoing assessment of the impact of the quadrivalent vaccine and potential, but unlikely, type replacement. This baseline data will help policy makers and implementers in policy decisions regarding future evaluation of the quadrivalent HPV vaccine in the Gambia. The data will also contribute to the literature on other HR-HPV genotypes causing cervical cancers in Africa and other continents. Study Limitations One of the study limitations is failure to amplify the internal housekeeping gene in a high number of FFPE samples. This could be attributed to the long storage of the samples. Some studies have elucidated difficulties in deparaffinising and extracting DNA from long storage FFPE samples. Another limitation encountered in this study was the poorly embedded tissues, not attached on the cassette or had little embedded tissues, which made tissue sectioning impossible. These samples were excluded from the study; therefore, the proposed sample size was not achieved. Declarations Ethics approval Ethics clearance was obtained from The Gambian Government Research and Publication ethics Committee. Consent to participant Not applicable Availability of data and materials Not applicable Competing Interest We have no competing interests. Funding This study was funded by Merck Sharp & Dohme through the Merck Investigator initiated Studies Program (MISP), Grant Number 59472 Authors’ contributions HB : contributed to the conception of the study, to the development of the proposal, molecular analysis, data analysis, writing of the draft manuscript and review of the manuscript. FC : contributed to the molecular laboratory analysis, review of the manuscript. HTB : contributed to the data analysis and review of the manuscript. OL : Contributed to the histology laboratory analysis and review of the manuscript. ATS : Contributed to the histology laboratory analysis and review of the manuscript. PTK : Contributed to the conception of the study, to the development of the proposal and review of the manuscript. All authors read and approved the final manuscript. Acknowledgements We would like to acknowledge Ramatoulie Secka, Mustapha Kanteh, Mariama Jammeh, Lucy Prom and the staff of the Pathology lab for their valuable support in retrieving the cervical cancer FFPE blocks and the request forms. We are also grateful to the Management of the Edward Francis Small Teaching Hospital for granting us the request to use the archived samples. References Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021:71:209–49. Stelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob Health. 2020; 20:30459-9 IOC/IARC: Gambia Human papillomavirus and related cancers, Fact sheet. 2023; https://hpvcentre.net/statistics/reports/GMB_FS.pdf IARC (International Agency for Research on Cancer). A review of human carcinogens. Part B: Biological agents/IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human papillomaviruses, IARC monographs on the evaluation of carcinogenic risks to humans. 2011;100B:255-313 de Martel C, Plummer M, Vignat J et al. Worldwide burden of cancer attributable to HPV by site, country, and HPV type. Int J Cancer. 2017; 141:664 – 670 Smith JS, Lindsay L, Hoots B et al. Human papillomavirus type distribution in invasive cervical cancer and high‐grade cervical lesions: a meta‐analysis update. Int J Cancer, 2007; 121:621-632 Clifford GM, Tully S, Franceschi S. Carcinogenicity of human papillomavirus (HPV) types in HIV-positive women: a meta-analysis from HPV infection to cervical cancer. Clin Infect Dis. 2017; 64:1228-1235. Bah Camara H, Anyanwu M, Wright, Kimmitt PT. Human papillomavirus genotype distribution and risk factor analysis in reproductive age women in urban Gambia. J Med Microbiol. 2018; 67:1645 -1654 Wall SR, Scherf CF, Morison L et al. Cervical human papillomavirus infection and squamous intraepithelial lesions in rural Gambia, West Africa: viral sequence analysis and epidemiology. Br J Cancer. 2005; 93:1068- 1076 Witkiewicz A K, Wright T C, Ferenczy A, Ronnett B M, Kurman R J. Carcinoma and other tumours of the Cervix, Blaustein's Pathology of the Female Genital Tract. Springer. 2011;254-295 Anna-Barbara M. Natural History of HPV Infection in Adolescents and Relationship to Cervical Cancer, Molecular Pathology of Gynaecologic Cancer, Totowa, New Jersey, Humana Press. Springer. 2007;103-112. Castellsague X. Natural history and epidemiology of HPV infection and cervical cancer. Gynecol Oncol. 2008;110(3 Suppl 2): S4-7 Niane K, Diagne Diop C T, Dia G et al. Human papilloma virus genotypes associated with cervical cancer in Senegal. Biomed Res Rev 2021; 5: 1- 6. Okolo C, Franceschi S, Adewole I, Thomas J O et al. Human papillomavirus infection in women with and without cervical cancer in Ibadan, Nigeria. Infect Agent Cancer. 2010; 5:24. Howitt B E, Herfs M, Tomoka T, Kamiza S et al. Comprehensive Human Papillomavirus Genotyping in Cervical Squamous Cell Carcinomas and Its Relevance to Cervical Cancer Prevention in Malawian Women. J Glob Oncol. 2017; 3: 227-234. Denny L, Adewole I, Anorlu R, Dreyer G, Moodley M, Smith T et al. Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-Saharan Africa. Int J Cancer. 2014; 134:1389-1398 Dybikowska A, Licznerski P, Podhajska A. HPV detection in cervical cancer patients in northern Poland. Oncology Reports. 2002;9(4):871-874 Mahmoodi P, Motamedi H, Abad Shapouri M R S, Shehni M B, Kargar M. Molecular Detection and Typing of Human Papillomaviruses in Paraffin-Embedded Cervical Cancer and Precancer Tissue Specimens. Iran J Cancer Prev. 2016; 9: e3752 Biedermann K, Dandachi N, Trattner M, Vogl G, Doppelmayr H, Moré E et al. Comparison of Real-Time PCR Signal-Amplified in Situ Hybridization and Conventional PCR for Detection and Quantification of Human Papillomavirus in Archival Cervical Cancer Tissue. J Clin Microbiol. 2004; 42:3758-3765 Garland S M, Tabrizi S. Methods for HPV Detection: Polymerase Chain Reaction Assays, Emerging Issues on HPV Infections, From Science to Practice. Basel Karger. 2006; 63-72. de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE et al. Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010; 11: 104 Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type, and year of publication. Int J Cancer 2011;128: 927-935 Lagheden C, Eklund C, Lamin H, Kleppe SN, Lei J et al. Nationwide comprehensive human papillomavirus (HPV) genotyping of invasive cervical cancer. Br J Cancer 2008;118: 1377-1381 Liao L, Cheng H, Zeng F, Zhou W, Ding Y. Prevalence and distribution of human papillomavirus genotypes among women with high-grade squamous intraepithelial lesion and invasive cervical cancer in Ganzhou, China. J Clin Lab Anal 2019; 33: e22708. International Agency for Research on Cancer (IARC). Handbooks of cancer prevention Vol 10: cervix cancer screening. 2005; Muñoz N, Castellsagué X, Berrington de González A, Gissmann L Chapter 1: HPV in the etiology of human cancer. Vaccine. 2006; 24:1-10 Salazar K L, Zhou H S, Xu J, Peterson L E, Schwartz M R, Mody D R et al. Multiple Human Papillomavirus Infections and Their Impact on the Development of High-Risk Cervical Lesions. Acta Cytologica. 2015;59::391-398 Missaoui N, Hmissa S, Trabelsi A, Tahar Yacoubi M, Nouira A et al. Prevalence of HPV infection in precancerous and cancerous lesions of the uterine cervix in Tunisia. Ann Biol Clin (Paris) 2010; 68: 297-303 Awua A K, Sackey S T, Osei Y D, Asmah R H, Wiredu E K. Prevalence of human papillomavirus genotypes among women with cervical cancer in Ghana. Infectious Agents and Cancer. 2016; 11:4. Zohoncon T M, Quedraogo T C, Brun L V S, Obiri-Yeboah D, Djigma W F, Kabibou S et al. Molecular Epidemiology of High-Risk Human Papillomavirus in High-Grade Cervical Intraepithelial Neoplasia and in Cervical Cancer in Parakou, Republic of Benin. Pakistan Journal of Biological Sciences. 2016; 19:49-56 IARC Handbooks of Cancer Prevention.2022; vol 18: https://publications.iarc.fr Bah Camara H, Anyanwu M, Mattiuzzo G, Gillard L, Wright E, Kimmitt, PT. Human Papillomavirus Sero-prevalence and Sexual Attitudes Amongst a Cohort of HIV Positive Women in The Gambia. 2018b. ASM Microbe : WestminsterResearch Tables Table 1: HPV genotype Distribution in Cervical Cancers identified by Histotype and Patient Age. Squamous cell carcinoma Adenocarcinoma Carcinoma in-situ Total HPV positive cases (n) HPV Prevalence (%) HPV positive cases (n) HPV Prevalence (%) HPV positive cases (n) HPV Prevalence (%) HPV positive cases (n) HPV Prevalence (%) All 97/104 93.3 5/104 4.8 2/104 1.9 104/119 87.4 Age (years) 21- 31 3/97 3.1 0 0 0 0 3/104 2.9 32-42 27/97 27.8 1/5 20.0 2/2 100 30/104 28.8 43-53 28/97 28.8 1/5 20.0 0 0 29/104 27.9 54-64 23/97 23.7 1/5 20.0 0 0 24/104 23.1 65-75 14/97 14.4 1/5 20.0 0 0 15/104 14.4 76-86 2/97 2.1 1/5 20.0 0 0 3/104 2.9 HPV type 16 53 54.6 1 20.0 2 1.9 56 53.8 18 14 14.4 2 40.0 0 0 16 15.4 16 /18 4 4.1 0 0 0 0 4 3.8 16/others-HR-HPV 7 7.1 1 20.0 0 0 8 6.7 18/ others-HR-HPV 1 1.0 1 20.0 0 0 2 1.9 Others-HR-HPV 18 18.5 0 0 0 0 18 17.3 Table 2; Association between Age, HPV Genotype and Cervical Cancer Variable Age in years n (%) Fisher’s exact test P-value 21 - 31 32 - 42 43 – 53 54 - 64 65 - 75 76 - 86 Diagnosis (n = 338) Cervical Cancer 11 (3.3) 82 (24.3) 100 (29.6) 79 (23.4) 45 (13.3) 9 (2.7) 11.4 0.023* Not Cervical Cancer 1 (0.3) 4 (1.2) 3 (0.9) 3 (0.9) - - HPV Result (n = 119) Positive 3 (2.5) 30 (25.2) 29 (24.4) 24 (20.2) 15 (12.6) 3 (2.5) 2.4 0.790 Negative - 3 (2.5) 6 (5.0) 3 (2.5) 2 (10.5) 1 (0.8) HPV Genotype (n =104) HPV16 1 (0.9) 15 (14.4) 19 (18.3) 10 (9.6) 11 (10.6) - 32.9 0.038* HPV 18 1 (0.9) 7 (6.7) 2 (1.9) 4 (3.8) 2 (1.9) - HPV 16 /18 - 1 (0.9) 2 (1.9) 1 (0.9) - - HPV 16 /other HR-HPV - - 4 (4.8) 2 (1.9) 1 (0.9) 1 (0.9) HPV 18 / other HR- HPV - - - 1 (0.9) - 1 (0.9) Other HR-HPV 1 (0.9) 7 (6.7) 2 (1.9) 6 (5.8) 1 (0.9) 1 (0.9) Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Sep, 2024 Read the published version in Infectious Agents and Cancer → Version 1 posted Editorial decision: Revision requested 24 May, 2024 Reviews received at journal 24 May, 2024 Reviewers agreed at journal 02 May, 2024 Reviewers invited by journal 29 Apr, 2024 Editor assigned by journal 22 Apr, 2024 Submission checks completed at journal 22 Apr, 2024 First submitted to journal 18 Apr, 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. We do this by developing innovative software and high quality services for the global research community. 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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-4289490","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":293884182,"identity":"913bf884-a1dc-48a2-92a1-768b18e48939","order_by":0,"name":"Haddy Bah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYBACAyCSYGxgSOCH8JlJ0CLZwEyqFoMDxGoxZz+88TbvDrs84xv5h18wVFgnNvCvTsCrxbInrdia90xysdmNZDYLhjPpiQ0Sbzfgd9iBHDNp3jbmxG1ALQaMbYeBWs4S0HL+DUhLfeLmGSAt/4jRcgNsy+HEDRLJzA8YG4Ba+HsJaXlWbDn3zPHEGWcemzEkHEs3bpPgJeSw5I033u6oTuxvT3z84UONtWw/PwGHgQATD4Rmk0iAkwQA4w8IzfwBTPEfIKxlFIyCUTAKRhQAAFmfTvIDjlAsAAAAAElFTkSuQmCC","orcid":"","institution":"University of The Gambia","correspondingAuthor":true,"prefix":"","firstName":"Haddy","middleName":"","lastName":"Bah","suffix":""},{"id":293884183,"identity":"589670a1-f0d2-4105-b915-35fe2bda1344","order_by":1,"name":"Foday Ceesay","email":"","orcid":"","institution":"Edward Francis Small Teaching Hospital","correspondingAuthor":false,"prefix":"","firstName":"Foday","middleName":"","lastName":"Ceesay","suffix":""},{"id":293884184,"identity":"f4e4636b-1e82-47e0-82f3-167cd135016b","order_by":2,"name":"Ousman Leigh","email":"","orcid":"","institution":"The American International University, West Africa","correspondingAuthor":false,"prefix":"","firstName":"Ousman","middleName":"","lastName":"Leigh","suffix":""},{"id":293884185,"identity":"f25df253-a8b7-4569-b364-2ef91d754f48","order_by":3,"name":"Haddy Tunkara Bah","email":"","orcid":"","institution":"University of The Gambia","correspondingAuthor":false,"prefix":"","firstName":"Haddy","middleName":"Tunkara","lastName":"Bah","suffix":""},{"id":293884186,"identity":"9567368c-4834-49f0-8e66-82a4e71f1d49","order_by":4,"name":"Ahmad Tejan Savage","email":"","orcid":"","institution":"Edward Francis Small Teaching Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ahmad","middleName":"Tejan","lastName":"Savage","suffix":""},{"id":293884188,"identity":"d1941168-e6c2-4746-bfc2-7cb79ea6670e","order_by":5,"name":"Patrick.T. Kimmitt","email":"","orcid":"","institution":"University of Westminster","correspondingAuthor":false,"prefix":"","firstName":"Patrick.T.","middleName":"","lastName":"Kimmitt","suffix":""}],"badges":[],"createdAt":"2024-04-18 18:59:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4289490/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4289490/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13027-024-00601-7","type":"published","date":"2024-09-12T15:58:19+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55526858,"identity":"1f4a381c-fadd-4f49-883a-101a2b6214c9","added_by":"auto","created_at":"2024-04-29 14:58:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":26271,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSample sectioning and human papillomavirus (HPV) testing for archived FFPE tissue blocks, received from Department of Laboratory Medicine, Histology unit, EFSTH.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4289490/v1/8d1f2986a51030d2ae1293d8.png"},{"id":55526857,"identity":"abd7da3f-0af6-467f-9865-06ed6b8936c1","added_by":"auto","created_at":"2024-04-29 14:58:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":18057,"visible":true,"origin":"","legend":"\u003cp\u003eHPV prevalence in the different ethnicities diagnosed with cervical cancer in The Gambia.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4289490/v1/c0d0fc7e0fcbd6ae08cbcf22.png"},{"id":64619549,"identity":"7f2fc707-0000-4e16-83f3-9b0d07da6046","added_by":"auto","created_at":"2024-09-16 16:15:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":799330,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4289490/v1/dff60134-638b-4a69-b20a-e74f4d71278c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Human papillomavirus type-specific distribution in cervical intraepithelial neoplasia and cancer in The Gambia prior to HPV immunization programme: A baseline for monitoring the quadrivalent vaccine","fulltext":[{"header":"Background","content":"\u003cp\u003eGlobally, cervical cancer is the fourth most common cancer among women with over 604,000 new cases and approximately 340,000 deaths reported in 2020 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, in developing countries, cervical cancer accounts for more than 85% of the global cervical cancer deaths [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The high cases of cervical cancer observed in developing countries may be attributed to low awareness and limited resources to successfully implement nationwide screening programs. Furthermore, the global mortality rate reported from cervical cancer is almost 10 times greater in the developing countries than in developed countries. This is mainly due to late presentation combined with inadequate access to cancer chemotherapy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the Gambia, cervical cancer ranks as the most frequent cancer among reproductive aged women 15\u0026ndash;44 years with an age standardised incidence rate of 42.9 and age standardised mortality rate of 33.9 per 100,000, respectively [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Current estimates indicate that every year 286 women in the Gambia are diagnosed with cervical cancer and approximately 70% die from the disease.\u003c/p\u003e \u003cp\u003ePersistent infection with high-risk human papillomavirus (HR-HPV) genotypes has been identified as the cause for the development of approximately 90% of cervical cancer cases. There are at least 15 HR-HPV genotypes that are known to be associated with cervical cancer, namely: HPV 16,18, 31,33,35,39,45,51,52,53,56,58,59,66 and 68 [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In an attempt to reduce the burden of HPV infection, three recombinant HPV prophylactic vaccines have been developed: a bivalent vaccine that targets HR-HPV genotypes16, 18, a quadrivalent vaccine against HR-HPV 16, 18 and low risk (LR) HPV 6 and 11, and Gardasil 9, which targets 7 HR-HPV genotypes 16, 18, 31, 33, 45, 52, 58 and LR-HPV, 6 and 11. HPV16 and HPV18 genotypes have the strongest association with cervical cancer with international studies reporting their presence in around 70% of cervical cancers [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, the distribution of other HR-HPV genotypes among cervical cancers across continents and even within Africa has been reported [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe Gambia is a small country situated in West Africa with a population size of less than 2.5\u0026nbsp;million; it is divided into namely: Banjul, the capital city, kanifing Municipal, Western, Lower River, North Bank, Central River, and Upper River Regions. Both Kanifing Municipal and Western Region are closer to the capital city, Banjul. The quadrivalent HPV vaccine was introduced in the Gambia in 2019 targeting girls aged 9\u0026ndash;14 years residing in the Kanifing Municipality and the Western Region. A vaccine coverage of 83% was achieved for the first dose. However, in 2021, the second dose coverage was about 30%. Although, there is data on the distribution of circulating HPV genotypes in the Gambia [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], this is the first baseline study characterising HPV genotypes in archived formalin fixed paraffin embedded (FFPE) biopsy cervical cancer tissues. The primary objectives of this study were to retrospectively assess the prevalence of HPV in archived FFPE cervical biopsy tissues with cervical cancer and to determine if there is any difference in the distribution of HR-HPV 16 and 18 genotypes in cervical cancerous cases in the Gambia comparison with the global distribution.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003e \u003cb\u003eSample selection and collection\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eThe Edward Francis Small Teaching Hospital (EFSTH) is the only tertiary referral hospital for patients or specimens with any form of suspected cancer in The Gambia. The Pathology department maintains a register where all received and processed tissue samples are recorded. This register was used to select paraffin-embedded formalin-fixed cervical tissues of women who were referred to the Pathology unit, Banjul, between January 2013 and December 2022 and diagnosed histologically with high grade precursor lesion (CIN III, high grade squamous Intraepithelial lesion (HSIL), or carcinoma in situ) or cervical cancer (adenocarcinoma, adenosquamous carcinoma or any form of squamous cell carcinoma) for this study. Formalin fixed paraffin embedded (FFPE) tissue blocks that are attached to the cassette, properly stored, and have all the relevant clinical data were selected for processing. Haematoxylin Eosin (H \u0026amp;E) stained slides of these paraffin blocks were examined for cancerous tissues and\u003c/p\u003e \u003cp\u003everified by the department Pathologist.\u003c/p\u003e \u003cp\u003eAll archived Atypical Squamous Cells of Undetermined Significance (ASCUS), CIN1/2\u003c/p\u003e \u003cp\u003esamples, inadequate tissue material and those with missing clinical data were excluded from processing.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eTissue Sectioning\u003c/h2\u003e \u003cp\u003eA total of 338 FFPE tissue samples with either HGSIL or cervical cancer were retrieved from the pathology department. A hundred and fifteen (115) of these samples had a small number of embedded tissues and were difficult to section. A total of two hundred and twenty-three (223) samples were adequate for sectioning (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). To avoid cross-contamination from other specimens, the microtome stage and forceps were cleaned with xylene followed by ethanol, and a fresh blade and a new container of water for floating sections was used for each paraffin block. Sixty (60\u0026micro;) micro of tissue samples were sectioned from each paraffin block.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e: \u003cb\u003eSample sectioning and human papillomavirus (HPV) testing for archived FFPE tissue blocks, received from Department of Laboratory Medicine, Histology unit, EFSTH.\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eHPV DNA extraction\u003c/h2\u003e \u003cp\u003eNucleic acid was extracted from the FFPE tissue samples using the AmpFire HPV kit (Atila Biosystems). The extraction process consists of lysing of the 60 \u0026micro; tissue samples with solution A (Catalog number PRMVR \u0026minus;\u0026thinsp;10) and a lysis buffer. Briefly, the tubes were vortexed for 10 seconds, followed by a brief spin to bring down all the liquid at the bottom of the tube. The tubes were incubated in a 95\u003csup\u003eO\u003c/sup\u003eC dry heat block for 1hr 30 minutes with a brief spin after the first 45 mins of incubation. After the incubation, the tubes were allowed to cool down at room temperature, vortexed and briefly spun. The supernatant containing the purified nucleic acid was transferred into microtubes for HPV detection and genotyping. To quality control the extraction process, molecular grade water was used as an internal control.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eHPV detection and genotyping\u003c/h2\u003e \u003cp\u003eHPV detection was carried out using AmpFire HPV 16/18/HR assay (Atila Biosystems, Line\u003c/p\u003e \u003cp\u003egene 9200). The test kit is designed for molecular diagnostic in vitro detection and typing of\u003c/p\u003e \u003cp\u003e15 high-risk human papillomaviruses (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59,\u003c/p\u003e \u003cp\u003e66, 68) from DNA preparations. It allows simultaneous identification of HPV 16 and 18 and\u003c/p\u003e \u003cp\u003egrouped the rest of the HR-HPV (31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) as other HR-HPV. The test system is based on detection of the viral genomic DNA including the viral oncogenes E6/E7 using high-risk HPV specific primers and fluorescent probes under isothermal condition. The Atila Biosystem software evaluates all amplification signals and generates the test results. An additional primer system that amplifies a region of the HPV genomic DNA is integrated into the test system. This serves as a positive control for the DNA preparation. Both positive and negative test controls were included in each run. In addition to the test controls, a molecular grade water was run alongside the controls as an in-house negative control. Samples that failed to amplify the internal housekeeping gene were classified as inadequate or invalid test result. All inadequate and HPV negative samples were rescreened using a new sectioned tissue.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eEpidemiological data was stored using Epi-Info version 7 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/epiinfo\u003c/span\u003e\u003cspan address=\"https://www.cdc.gov/epiinfo\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) software and was linked to both the clinical data and the HPV genotyping results. The final data base was analysed using IBM SPSS version 21.0. Analysis was primarily descriptive with proportions of each HPV type detected in the cancers. Fisher\u0026rsquo;s exact test was used to determine the primary outcomes of interest at a p-value of \u0026lt;\u0026thinsp;0.05 and 95% confidence intervals (CI) were considered statistically significant. Fisher\u0026rsquo;s test was used to find any relation between HPV types and degree of cytopathologic abnormalities.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe mean age of women that samples were collected from was 50.4 years (standard deviation, SD\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6, range 13\u0026ndash;85). Out of the 338 participants, 326 (96.4%) of them were diagnosed with cervical cancer; 300 (92%) of these cancers were squamous cell carcinoma, 14 (4.3%) adenocarcinoma, 11 (3.4%) carcinoma in-situ and 1 (0.3%) with CIN III with high degree of invasive suspicious of invasive carcinoma.\u003c/p\u003e \u003cp\u003eOf the 119 samples that were adequate for HPV DNA screening, 104 were HPV positive and 15 were HPV negative, thus giving HPV positivity rate of 87% (104/119). In single infection, HPV 16 accounts for 53% (56/104) of the HPV genotypes found in the cervical tissues, HPV 18 accounts for 15.4% (16/104), and other HR-HPV17.3% (18/104) (Table\u0026nbsp;1). Furthermore, HPV 16 and 18 genotypes combined accounts for 69.2% of the cervical cancer cases. In multiple infections, double infections were observed in 14 cases with a prevalence rate as follows: HPV genotype 16 /18 (3.8%, 4/104), HPV genotype 16 and other HR-HPV (6.7%, 8/104), HPV 18 and other HR-HPV (1.9%, 2/104).\u003c/p\u003e \u003cp\u003eA majority 93% (97/104) of cervical samples diagnosed with squamous cell carcinoma were HPV positive with HPV genotype 16 being more prevalent (54.6%, 53/97), followed by others - HR-HPV (18.6%, 18/97), and HPV 18 accounting for 14.4%, (14/97) of the squamous cell carcinoma cases, respectively.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;1: \u003cb\u003eHPV Genotypes Distribution in Cervical Cancer identified by Histotype and\u003c/b\u003e\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient Age\u003c/h2\u003e \u003cp\u003eHPV distribution amongst the different age groups showed HPV 16 related cancer was more prevalent in the 43 \u0026minus;\u0026thinsp;53-year-old (18.3%), followed by 32\u0026ndash;42 aged group (14.4%) (Table\u0026nbsp;2). The results also showed that 39% of the cervical cancer biopsies that were HPV positive were from the Mandinka ethnicity, followed by the Jola (20%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The distribution of HPV related cervical cancer in the different regions of the country showed that approximately 52% and 32% of cases were from the West Coast Region (WCR) and Kanifing Municipal Council\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e(KMC) of the country, respectively. Fewer cases of HPV related cervical cancer were observed for the other regions and only 2% of HPV related cervical cancer cases were from the capital city, Banjul.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e: \u003cb\u003eA graph showing HPV prevalence amongst different ethnicities diagnosed with cervical cancer, Gambia\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eA bivariate analysis showed there was a significant association between participants\u0026rsquo; age with their diagnosis with cervical cancer (p\u0026thinsp;=\u0026thinsp;0.023) and HPV genotype (p\u0026thinsp;=\u0026thinsp;0.038) (Table\u0026nbsp;2). However, no significant association between ethnicity, residential area of the participants and their diagnosis with cervical cancer, HPV result and HPV genotype (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) were observed. The participants within the ages 43\u0026ndash;53 years had the highest frequency (n\u0026thinsp;=\u0026thinsp;100, 29.6) of cervical cancer diagnosis and with HPV Genotype 16 (n\u0026thinsp;=\u0026thinsp;19, 18.3%) as the most prevalent type. Fewer HPV positive cervical cancers were observed in the older age group (76\u0026ndash;86 years) (Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;2: Association between Age, HPV Genotype and Cervical Cancer\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePersistent infection with high -risk HPV genotypes has been identified as the most important aetiologic agent in the pathogenesis of cervical cancer [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Although, geographical variations in the prevalence of HPV DNA in cervical cancer biopsies, has been reported worldwide, the overall prevalence has been reported to be approximately 95% [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In this cross-sectional study of women diagnosed with cervical cancer from 2013\u0026ndash;2022, HPV prevalence was found to be 87% in the analysed cervical cancer tissues with HPV 16 genotype being the most frequent type detected (53.8%), followed by other HR-HPV genotype (17.3%), and HPV 18 genotype accounting for (15.4%) (Table\u0026nbsp;1). In addition, the combined prevalence of HPV 16 and 18 genotypes accounts for approximately 70% of the cervical cancer cases diagnosed in this study. However, a low HPV 16 carriage rate was observed in cervical swabs from reproductive aged women from Bah Camara et al (2018) study [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Their study identified other HR-HPV genotypes as the most common circulating type in urban Gambia. The high HPV prevalence rate of 87% found in this study is similar to other studies conducted in the neighbouring country, Senegal (90%, and in Nigeria (90.7%) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In addition, HPV studies carried out on FFPE samples in Malawi and South Africa also reported a high prevalence rate of 97% and 92%, respectively [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, countries including Poland and Iran reported a lower HPV prevalence rate in cervical cancer [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These differences in HPV prevalence in cervical cancer could be attributed to several factors which may include geographical variations, quality and quantity of samples, sensitivity and specificity of the methods used for DNA extraction and HPV detection [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe high prevalence (53%) of HPV16 reported in this FFPE study was consistent with other studies, as this genotype is the most prevalence type reported, globally [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Epidemiological, clinical, and molecular studies have shown that HPV 16 and HPV18 genotypes are combinedly responsible for almost 70% of cervical cancers [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The combined prevalence rate (approximately 70%) of HPV 16 (53.8%) and HPV 18 (15.4%) genotypes reported in this retrospective cross-sectional study corresponds to the estimate of the global distribution of these genotypes responsible for causing cervical cancers, worldwide. They are the most prevalent and most potent carcinogenic viruses, and their probability of disease progression and persistence is significantly higher than other high risk HPV genotypes [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Furthermore, in the 97 tissues diagnosed with squamous carcinoma, HPV 16 genotype accounts for 54.6% (53/97) (Table\u0026nbsp;1). This result agrees with that of Wall et al., carried out in the Gambia [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and Missaoui et al., carried out in Tunisia, North Africa [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Both studies found that HPV 16 is the most frequent genotype among invasive squamous cell carcinomas. However, some studies have reported that other HR-HPV genotypes other than HPV 16 are most common HPV type detected in cervical cancer [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. A study carried out in Parakou, Benin Republic, reported that HPV 16 genotype was not detected in any of the cervical cancer cases, and HPV 39 was the most common genotype detected in their study [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. This could be due to geographical variation and /or genotype specific replacement as 15% of cervical cancers are reported to be caused by other HR-HPV [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAn observation in this study was the high proportion (17.3%) of single infections with other HR-HPV and (6.7%) combined infections of HPV 16 with other HR-HPV genotypes found in the cervical cancer tissue samples. This finding agrees with the result from Bah Camara et al., study that found other HR-HPV genotypes in cervical samples of HIV positive women diagnosed with cervical cancer in The Gambia [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Other studies have also shown that apart from HPV 16 and 18 genotypes, other HR-HPV genotypes that the quadrivalent HPV vaccine does not offer protection against causes cervical cancers [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Although, the Gambia is currently administering the quadrivalent vaccine which targets HPV genotypes 6, 11, 16 and 18, there is a need to switch to the nonavalent HPV vaccine which targets an additional 5 other HR-HPV genotypes (HPV 31, 33, 45, 52, and 58) which are associated of causing 15% of cervical cancers, globally [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHPV DNA negative results was found in 12.6% (15/119) histologically diagnosed cervical cancer cases. This could be due to the rare cases of non-HPV related cervical cancer or integration of the viral genome into the host chromosome, which could lead to changes in the\u003c/p\u003e \u003cp\u003egenes the PCR primers target.\u003c/p\u003e \u003cp\u003eOf the 326 cervical cancer cases histologically diagnosed in The Gambia, cervical cancer was most common in 43\u0026ndash;53-year aged women (29.6%, 100/326). However, HPV related cervical cancer was more prevalent in the 32\u0026ndash;42 year (28.8%, 30/104), followed by 43\u0026ndash;53 year (27.9%, 29/104) aged women. This finding further shows that women that are mostly affected with cervical cancer in the Gambia are in their mid-adult lives (32\u0026ndash;53 years) and possibly having young families. A significant association was found between cervical cancer diagnosis and age (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and HPV genotype (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;2). The high (39%) HPV related cervical cancer observed in the Mandinka ethnic is not surprising as it is the most predominate ethnicity of the country. However, no significance association was found between HPV genotype, cervical cancer diagnoses and ethnicity. Another interesting finding from this study was that less histologically diagnosed cervical cancer cases was observed for the Northern, Central, and Upper Regions of the country compared to the Western (52%) and (32%) Kanifing Municipal Regions. These differences could be attributed to several factors among which include access, and proximity of the only histology department in the country, which is situated at the teaching hospital in Banjul, the capital city. The low (2%) prevalence rate of histologically diagnosed cervical cancer observed in the capital city could also be attributable to residents having access to early cervical cancer screening and pre cancer management, which is also offered in the teaching hospital in Banjul. This highlight the need to decentralise cervical cancer screening in the country for easy access and management of precancerous lesions, and prompt treatment options.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study showed that the overall frequency of HPV genotypes detected in women with cervical cancer in The Gambia was high. HPV 16, other HR-HPV, and HPV 18 genotypes were the most prevalence types found causing cervical cancer in a single infection. HPV 16 and other HR-HPV were the most common genotypes in multiple infections. In view of these results, the use of the Gardasil-9\u0026reg; (nonavalent) vaccine could provide a more effective cervical cancer prevention in The Gambia. Furthermore, monitoring the changes in HPV genotype distribution will allow ongoing assessment of the impact of the quadrivalent vaccine and potential, but unlikely, type replacement. This baseline data will help policy makers and implementers in policy decisions regarding future evaluation of the quadrivalent HPV vaccine in the Gambia. The data will also contribute to the literature on other HR-HPV genotypes causing cervical cancers in Africa and other continents.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStudy Limitations\u003c/h2\u003e \u003cp\u003eOne of the study limitations is failure to amplify the internal housekeeping gene in a high number of FFPE samples. This could be attributed to the long storage of the samples. Some studies have elucidated difficulties in deparaffinising and extracting DNA from long storage FFPE samples. Another limitation encountered in this study was the poorly embedded tissues, not attached on the cassette or had little embedded tissues, which made tissue sectioning impossible. These samples were excluded from the study; therefore, the proposed sample size was not achieved.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics clearance was obtained from The Gambian Government Research and Publication ethics Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participant\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by Merck Sharp \u0026amp; Dohme through the Merck Investigator initiated Studies Program (MISP), Grant Number 59472\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eHB\u003c/strong\u003e: contributed to the conception of the study, to the development of the proposal, molecular analysis, data analysis, writing of the draft manuscript and review of the manuscript.\u0026nbsp;\u003cstrong\u003eFC\u003c/strong\u003e: contributed to the molecular laboratory analysis, review of the manuscript.\u0026nbsp;\u003cstrong\u003eHTB\u003c/strong\u003e: contributed to the data analysis and review of the manuscript.\u0026nbsp;\u003cstrong\u003eOL\u003c/strong\u003e: Contributed to the histology laboratory analysis and review of the manuscript.\u0026nbsp;\u003cstrong\u003eATS\u003c/strong\u003e: Contributed to the histology laboratory analysis and review of the manuscript.\u0026nbsp;\u003cstrong\u003ePTK\u003c/strong\u003e: \u0026nbsp;Contributed to the conception of the study, to the development of the proposal and review of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge Ramatoulie Secka, Mustapha Kanteh, Mariama Jammeh, Lucy Prom and the staff of the Pathology lab for their valuable support in retrieving the cervical cancer FFPE blocks and the request forms. We are also grateful to the Management of the Edward Francis Small Teaching Hospital for granting us the request to use the archived samples.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021:71:209\u0026ndash;49.\u003c/li\u003e\n \u003cli\u003eStelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob Health. 2020; 20:30459-9\u003c/li\u003e\n \u003cli\u003eIOC/IARC: Gambia Human papillomavirus and related cancers, Fact sheet. 2023; https://hpvcentre.net/statistics/reports/GMB_FS.pdf\u003c/li\u003e\n \u003cli\u003eIARC (International Agency for Research on Cancer). A review of human carcinogens. Part B: Biological agents/IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human papillomaviruses, IARC monographs on the evaluation of carcinogenic risks to humans. 2011;100B:255-313\u003c/li\u003e\n \u003cli\u003ede Martel C, Plummer M, Vignat J et al. Worldwide burden of cancer attributable to HPV by site, country, and HPV type. Int J Cancer. 2017; 141:664 \u0026ndash; 670\u003c/li\u003e\n \u003cli\u003eSmith JS, Lindsay L, Hoots B et al. Human papillomavirus type distribution in invasive cervical cancer and high‐grade cervical lesions: a meta‐analysis update. Int J Cancer, 2007; 121:621-632\u003c/li\u003e\n \u003cli\u003eClifford GM, Tully S, Franceschi S. Carcinogenicity of human papillomavirus (HPV) types in HIV-positive women: a meta-analysis from HPV infection to cervical cancer. Clin Infect Dis. 2017; 64:1228-1235.\u003c/li\u003e\n \u003cli\u003eBah Camara H, Anyanwu M, Wright, Kimmitt PT. Human papillomavirus genotype distribution and risk factor analysis in reproductive age women in urban Gambia. J Med Microbiol. 2018; 67:1645 -1654\u003c/li\u003e\n \u003cli\u003eWall SR, Scherf CF, Morison L et al. Cervical human papillomavirus infection and squamous intraepithelial lesions in rural Gambia, West Africa: viral sequence analysis and epidemiology. Br J Cancer. 2005; 93:1068- 1076\u003c/li\u003e\n \u003cli\u003eWitkiewicz A K, Wright T C, Ferenczy A, Ronnett B M, Kurman R J. Carcinoma and other tumours of the Cervix, Blaustein\u0026apos;s Pathology of the Female Genital Tract. Springer. 2011;254-295\u003c/li\u003e\n \u003cli\u003eAnna-Barbara M. Natural History of HPV Infection in Adolescents and Relationship to Cervical Cancer, Molecular Pathology of Gynaecologic Cancer, Totowa, New Jersey, Humana Press. Springer. 2007;103-112.\u003c/li\u003e\n \u003cli\u003eCastellsague X. Natural history and epidemiology of HPV infection and cervical cancer. Gynecol Oncol. 2008;110(3 Suppl 2): S4-7\u003c/li\u003e\n \u003cli\u003eNiane K, Diagne Diop C T, Dia G et al. Human papilloma virus genotypes associated with cervical cancer in Senegal. Biomed Res Rev 2021; 5: 1- 6.\u003c/li\u003e\n \u003cli\u003eOkolo C, Franceschi S, Adewole I, Thomas J O et al. Human papillomavirus infection in women with and without cervical cancer in Ibadan, Nigeria. Infect Agent Cancer. 2010; 5:24.\u003c/li\u003e\n \u003cli\u003eHowitt B E, Herfs M, Tomoka T, Kamiza S et al. Comprehensive Human Papillomavirus Genotyping in Cervical Squamous Cell Carcinomas and Its Relevance to Cervical Cancer Prevention in Malawian Women. J Glob Oncol. 2017; 3: 227-234.\u003c/li\u003e\n \u003cli\u003eDenny L, Adewole I, Anorlu R, Dreyer G, Moodley M, Smith T et al. Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-Saharan Africa. Int J Cancer. 2014; 134:1389-1398\u003c/li\u003e\n \u003cli\u003eDybikowska A, Licznerski P, Podhajska A. HPV detection in cervical cancer patients in northern Poland. Oncology Reports. 2002;9(4):871-874\u003c/li\u003e\n \u003cli\u003eMahmoodi P, Motamedi H, Abad Shapouri M R S, Shehni M B, Kargar M. Molecular Detection and Typing of Human Papillomaviruses in Paraffin-Embedded Cervical Cancer and Precancer Tissue Specimens. Iran J Cancer Prev. 2016; 9: e3752\u003c/li\u003e\n \u003cli\u003eBiedermann K, Dandachi N, Trattner M, Vogl G, Doppelmayr H, Mor\u0026eacute; E et al. Comparison of Real-Time PCR Signal-Amplified in Situ Hybridization and Conventional PCR for Detection and Quantification of Human Papillomavirus in Archival Cervical Cancer Tissue. J Clin Microbiol. 2004; 42:3758-3765\u003c/li\u003e\n \u003cli\u003eGarland S M, Tabrizi S. Methods for HPV Detection: Polymerase Chain Reaction Assays, Emerging Issues on HPV Infections, From Science to Practice. Basel Karger. 2006; 63-72.\u003c/li\u003e\n \u003cli\u003ede Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE et al. Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010; 11: 104\u003c/li\u003e\n \u003cli\u003eLi N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type, and year of publication. Int J Cancer 2011;128: 927-935\u003c/li\u003e\n \u003cli\u003eLagheden C, Eklund C, Lamin H, Kleppe SN, Lei J et al. Nationwide comprehensive human papillomavirus (HPV) genotyping of invasive cervical cancer. Br J Cancer 2008;118: 1377-1381\u003c/li\u003e\n \u003cli\u003eLiao L, Cheng H, Zeng F, Zhou W, Ding Y. Prevalence and distribution of human papillomavirus genotypes among women with high-grade squamous intraepithelial lesion and invasive cervical cancer in Ganzhou, China. J Clin Lab Anal 2019; 33: e22708.\u003c/li\u003e\n \u003cli\u003eInternational Agency for Research on Cancer (IARC). Handbooks of cancer prevention Vol 10: cervix cancer screening. 2005;\u003c/li\u003e\n \u003cli\u003eMu\u0026ntilde;oz N, Castellsagu\u0026eacute; X, Berrington de Gonz\u0026aacute;lez A, Gissmann L Chapter 1: HPV in the etiology of human cancer. Vaccine. 2006; 24:1-10\u003c/li\u003e\n \u003cli\u003eSalazar K L, Zhou H S, Xu J, Peterson L E, Schwartz M R, Mody D R et al. Multiple Human Papillomavirus Infections and Their Impact on the Development of High-Risk Cervical Lesions. Acta Cytologica. 2015;59::391-398\u003c/li\u003e\n \u003cli\u003eMissaoui N, Hmissa S, Trabelsi A, Tahar Yacoubi M, Nouira A et al. Prevalence of HPV infection in precancerous and cancerous lesions of the uterine cervix in Tunisia. Ann Biol Clin (Paris) 2010; 68: 297-303\u003c/li\u003e\n \u003cli\u003eAwua A K, Sackey S T, Osei Y D, Asmah R H, Wiredu E K. Prevalence of human papillomavirus genotypes among women with cervical cancer in Ghana. Infectious Agents and Cancer. 2016; 11:4.\u003c/li\u003e\n \u003cli\u003eZohoncon T M, Quedraogo T C, Brun L V S, Obiri-Yeboah D, Djigma W F, Kabibou S et al. Molecular Epidemiology of High-Risk Human Papillomavirus in High-Grade Cervical Intraepithelial Neoplasia and in Cervical Cancer in Parakou, Republic of Benin. Pakistan Journal of Biological Sciences. 2016; 19:49-56\u003c/li\u003e\n \u003cli\u003eIARC Handbooks of Cancer Prevention.2022; vol 18: https://publications.iarc.fr\u003c/li\u003e\n \u003cli\u003eBah Camara H, Anyanwu M, Mattiuzzo G, Gillard L, Wright E, Kimmitt, PT. Human Papillomavirus Sero-prevalence and Sexual Attitudes Amongst a Cohort of HIV Positive Women in The Gambia. 2018b. ASM Microbe : WestminsterResearch\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: HPV genotype Distribution in Cervical Cancers identified by Histotype and Patient Age.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"702\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.974358974358974%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.64957264957265%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSquamous cell carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79202279202279%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAdenocarcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79202279202279%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eCarcinoma in-situ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.79202279202279%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003eHPV positive cases (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003eHPV Prevalence (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003eHPV positive cases (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003eHPV Prevalence (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003eHPV positive cases (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003eHPV Prevalence (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003eHPV positive cases (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003eHPV Prevalence (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003eAll\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e97/104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e93.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e5/104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e2/104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e104/119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e87.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e21- 31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e3/97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e3/104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e32-42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e27/97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e27.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1/5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e2/2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e30/104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e28.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e43-53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e28/97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e28.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1/5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e29/104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e27.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e54-64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e23/97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e23.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1/5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e24/104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e23.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e65-75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e14/97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e14.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1/5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e15/104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e14.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e76-86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e2/97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; 2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1/5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;3/104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;2.9\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHPV type\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e54.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e53.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e14.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e40.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e15.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e16 /18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e16/others-HR-HPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003e18/ others-HR-HPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9%\" valign=\"top\"\u003e\n \u003cp\u003eOthers-HR-HPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e17.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 2;\u003c/strong\u003e \u003cstrong\u003eAssociation between Age, HPV Genotype and Cervical Cancer\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"708\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"66.94915254237289%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge in years\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFisher\u0026rsquo;s exact test\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\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 width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e21 - 31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e32 - 42\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e43 \u0026ndash; 53\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e54 - 64\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e65 - 75\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e76 - 86\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis (n = 338)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\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 width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003eCervical Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e11 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e82 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e100 (29.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e79 (23.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e45 (13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e9 (2.7) \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e11.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.023*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNot Cervical Cancer\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\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 width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHPV Result (n = 119)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\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 width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\"\u003e\n \u003cp\u003e3\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e30\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(25.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e29\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(24.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e24\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(20.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e15\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\"\u003e\n \u003cp\u003e3\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(2.5) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e2.4 \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.790\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e3\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e6\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e3\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e2\u003csub\u003e\u0026nbsp;\u003c/sub\u003e(10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\"\u003e\n \u003cp\u003e1 (0.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\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 width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHPV Genotype\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n =104)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\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 width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\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 width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003eHPV16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e15 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e19 (18.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e10 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e11 (10.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 32.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003cstrong\u003e0.038*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHPV 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHPV 16 /18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHPV 16 /other HR-HPV\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003eHPV 18 / other HR- HPV\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOther HR-HPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\"\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e7 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e2 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e6 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.864406779661017%\"\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\"\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.169491525423728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.322033898305085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\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":"HPV genotype, human papilloma virus, Cervical cancer, HPV vaccines, Squamous carcinoma","lastPublishedDoi":"10.21203/rs.3.rs-4289490/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4289490/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePersistent infection with the high-risk human papillomavirus (HR-HPV) is associated with causing nearly 95% of cervical cancer and remains a worldwide concern. In the Gambia, cervical cancer is the leading cause of cancer deaths in women. Current estimates indicate that 286 women are annually diagnosed with cervical cancer with a fatality rate of 70%. In an attempt to address this, in 2019 the quadrivalent HPV vaccine was incorporated into the Gambia’s expanded programme on Immunisation. The aim of the study was to retrospectively assess the prevalence and distribution of high-risk HPV genotype in archived, formalin fixed paraffin embedded cervical biopsy tissues diagnosed with cervical cancer in the Gambia from year 2013 -2022.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod: \u003c/strong\u003eA total of 223 samples with histologically diagnosis of cervical cancer with adequate tissues were sectioned and deparaffinised, followed by HPV DNA extraction and the detection of HR-HPV by real-time multiplex PCR. The internal housekeeping gene was amplified in 119 samples, which were subsequently tested for HPV DNA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eHPV prevalence was found to be 87% (104 /119) in cervical cancer cases, 15 (12.6%) samples tested negative for HPV DNA. In single infections, HPV 16 genotype was the most frequent type in cervical cancer cases accounting for 53% (56/104), followed by other high risk HPV genotypes 17% (18/104), and HPV genotype 18 was found in 15% (16/104) of cervical cancer cases. HPV related cervical cancer was most common in the 32 -42 year (28.8%, 30/104) aged women. A significant association between age and diagnosis with cervical cancer (p = 0.023), and HPV genotype (p = 0.038) was observed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThere was no difference in the distribution of HPV 16 and 18 genotypes in cervical cancer cases in The Gambia in comparison with the global distribution. However, the high prevalence of single infections with other HR-HPV, and multiple infections with HPV 16 and other HR-HPV genotypes seen in this study, clearly shows that the nonavalent HPV vaccine could be more beneficial for The Gambia. This study provides The Gambia with a baseline data to use in policy decisions regarding future evaluation of the quadrivalent HPV vaccine in the country.\u003c/p\u003e","manuscriptTitle":"Human papillomavirus type-specific distribution in cervical intraepithelial neoplasia and cancer in The Gambia prior to HPV immunization programme: A baseline for monitoring the quadrivalent vaccine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-29 14:57:56","doi":"10.21203/rs.3.rs-4289490/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-24T11:23:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-24T09:02:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"69280932710502611301237250961121984606","date":"2024-05-02T09:31:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-29T16:03:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-22T06:01:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-22T06:01:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Infectious Agents and Cancer","date":"2024-04-18T18:55:54+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":"dbe75abb-38b9-4699-9487-0569eb7b5ced","owner":[],"postedDate":"April 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-16T16:09:36+00:00","versionOfRecord":{"articleIdentity":"rs-4289490","link":"https://doi.org/10.1186/s13027-024-00601-7","journal":{"identity":"infectious-agents-and-cancer","isVorOnly":false,"title":"Infectious Agents and Cancer"},"publishedOn":"2024-09-12 15:58:19","publishedOnDateReadable":"September 12th, 2024"},"versionCreatedAt":"2024-04-29 14:57:56","video":"","vorDoi":"10.1186/s13027-024-00601-7","vorDoiUrl":"https://doi.org/10.1186/s13027-024-00601-7","workflowStages":[]},"version":"v1","identity":"rs-4289490","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4289490","identity":"rs-4289490","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}