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- Springer Journals
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- Copyright © The Author(s) 2023
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- 1750-9378
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- 10.1186/s13027-023-00493-z
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Abstract
Background Cervical cancer is the third most common cancer among women worldwide, but particularly affects women living in sub‑Saharan Africa. Screening and vaccination programs are two prevention approaches that can reduce cervical cancer incidence. However, effective vaccination campaigns require better knowledge of the preva‑ lence of the main human papillomavirus (HPV ) genotypes reported in high‑ grade neoplastic lesions and invasive carcinomas in women. Methods All samples collected in this study were processed using standard histopathological methods with hae‑ matoxylin and eosin staining of the sections. Areas with abnormal cells were then identified. The HPV genotype was determined on the DNA extracted from the same sections using nested PCR followed by amplicon sequencing and real‑time PCR specific to five different HPV genotypes (16, 18, 33, 45 and 58). Results A total of 132 Gabonese patients with high‑ grade neoplastic lesions were included in this study; 81% were squamous cell carcinomas (SCC). At least one HPV was detected in 92.4% patients; HPV16 (75.4%) was the most fre‑ quent genotype, followed by HPV18, 58, 45, 33 and 35. Moreover, histological analysis showed that SCC samples had 50% and 58.2% stage III and IV tumor cells, respectively, according to the FIGO classification. Finally, 36.9% of these stage III and IV patients were less than 50 years old. Conclusions Our results confirm the high prevalence of HPV16 and 18 genotypes among high‑ grade lesions in Gabonese women. This study confirms the need for a national strategy for early screening of precancerous lesions associated with a broad national vaccination program among non‑sexually active women to significantly reduce the long‑term cancer burden. Keywords High‑ grade cervical lesions, Invasive cervical cancer, HPV, Gabon *Correspondence: Nicolas Berthet nicolas.berthet@pasteur.fr; nicolas.berthet@ips.ac.cn Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Moussavou‑Boundzanga et al. Infectious Agents and Cancer (2023) 18:16 Page 2 of 8 used. Overall, these studies have revealed a predomi- Introduction nance of the HPV16, 18 and 33 genotypes in cervical can- Cervical cancer is a major global public health issue. Of cers [9–11]. the estimated 570,000 new cases and 311,365 deaths in The objective of this study was to determine the prev - 2018, it is the third most common cancer among women alence of major HPV genotypes in all reported cases of worldwide, but particularly affects women living in devel - high-grade neoplastic lesions and invasive carcinomas at oping countries [1]. Approximately 85% of new cancer the Centre Hospitalier Universitaire d’Angondjé (CHUA) cases are reported in low- and middle-income countries. and the Hôpital des Instructions des Armées Omar Bongo The various screening programs, particularly those based Ondimba (HIAOBO)between 2012 and 2017 in Gabon. on the Papanicolaou smear, have reduced the rate of cer- The clinical stage of these lesions was determined and vical cancer in developed countries. However, the high virological investigations were performed using stand- rates of cervical cancer observed in developing countries ardized protocols common to all other consortium result from inadequate screening and treatment of pre- countries. cancerous lesions. To reduce this disparity, the WHO has set up a strat- egy to ensure that 90% of girls are fully vaccinated against Methods human papillomavirus (HPV) by the age of 15 and that Population 70% of women are tested for HPV at 35 and 45 years of A multi-center, cross-sectional study was conducted in age [2]. Although vaccination and screening are two pre- two hospitals in Libreville (Gabon), at the CHUA and at vention approaches, vaccination is probably the most the HIA OBO. Between 2012 and 2017, all women diag- effective in the long term given its extremely high pre - nosed histologically with either cervical intraepithelial ventive efficacy [3–5]. However, vaccination campaigns neoplasia 3 (CIN3), adenocarcinoma (ADC) or squa- mainly benefit younger generations of women and future mous cell carcinoma (SCC) were included in this study. generations; thus, several decades will pass before the The exclusion criteria for the study were as follows: (i) health effects of vaccination are observed in developing patients with a history of total uterine or cervical resec- countries. However, in the meantime, screening pro- tion or (ii) patients with a history of chemotherapy and grams can reduce the burden of cervical cancer more (iii) vaccinated patients. In addition, samples for which rapidly and benefit both current and future generations patient age was unavailable or not precisely known were of women. Thus, screening programs combined with vac - excluded. To avoid duplication, the names and date of cination are fundamental, because they are potentially birth of each patient were checked by two different tech - cost-effective and can reduce cervical cancer incidence nicians. All laboratory manipulations were carried out at and mortality rates [6]. the Centre Interdisciplinaire de Recherches Médicales de Given that epidemiological data on HPV in low- Franceville (CIRMF) in Gabon. income countries, particularly in sub-Saharan Africa (SSA), are difficult to compare, an African consortium Histological analysis from formalin‑fixed of five French-speaking African countries (Senegal, Ivory paraffin‑embedded (FFPE) tissue Coast, Cameroon, Gabon and Madagascar) was created The samples were processed using standard histo - under the aegis of the National Cancer Institute (INCa) pathological methods and evaluated by a certificated in France. The consortium focuses on providing a work - pathologist. All patients were staged according to the ing model to establish standardized research protocols International Federation of Gynecology and Obstetrics for the identification of HPV genotypes associated with (FIGO) staging system 2009 [12]. The abnormal cell per - high-grade invasive neoplasia intraepithelial lesions in centage was calculated by selecting the area where the women living in the consortium countries [7]. In these lesion was most representative on the slide and count- participating countries, cervical cancer is a major public ing at high magnification (× 400) out of 100 cells. Only health issue, and is generally the most common cancer these regions with abnormal tissue were used for DNA found in women. As in other Central African countries, extraction. cervical cancer is one of the leading cause of cancer mor- tality in Gabon and remains a priority for the authorities of this country for better management [8]. However, the Sample preparation for molecular analysis main challenge is to determine the prevalence of the dif- Depending on the size of the biopsy, five to seven sec - ferent HPV genotypes found in cervical cancer in Gabon. tions of 4 µm were cut from each FFPE block and placed Previous studies in Gabon have shown that the distribu- on a slide. The outer sections were used for histological tion of genotypes varies according to the type of popula- analysis and the inner sections were used for molecular tion studied, age group, histological status and methods investigations. Histological sections were stained with M oussavou‑Boundzanga et al. Infectious Agents and Cancer (2023) 18:16 Page 3 of 8 hematoxylin and eosin (H&E) and areas including abnor- Determination of infectious profile mal cells were identified. The result of any method was compiled independently. Specific HPV genotypes concurrently detected by both RealTime PCR and nested PCR were regarded as valid results. In the event of a discordant result, the result was DNA extraction grouped into High risk, Low risk, and uncertain-risk Before extraction, abnormal tissue sections from the five groups according to previously described criteria [14]. inner slides (each 4-μm thick) were placed in a 1.5 ml An individual sample was considered co-infections if at Eppendorf tube. Precaution was taken to avoid cross- least two different genotypes were detected by either of contamination, including changing cutting blades and the two methods. changing gloves between each preparation. Then, each block was deparaffinized. To dissolve the paraffin, blocks were treated with toluene for 2 min, and then immersed Statistical analysis in 100% alcohol for 2 min to remove the toluene. Then, Statistical analysis were performed using R version 3.2.2. total DNA was extracted using a QIAamp DNA FFPE Summary statistics for age at histological diagnosis (n, Tissue Kit (Qiagen, Redwood City, CA, USA) accord- mean, standard error, median, minimum and maximum) ing to the manufacturer’s instructions. Extracted DNA and cervical lesion (n; proportion) were produced. The was stored at − 20 °C until analysis. DNA was quanti- associations between HPV infection and both age group- fied using a Qubit dsDNA BR Assay kit with the Qubit ings and severity of histological diagnosis have been 2.0 fluorimeter (Life Technologies, Carlsbad, CA, USA). tested by chi-square at 95% confidence level. DNA quality was assessed using real-time qPCR to amplify a 107 bp fragment of the glyceraldehyde-3-phos- Results phate dehydrogenase (GADPH) housekeeping gene. Characteristics of the study population Among the 191 patients followed in the two laboratories between 2012 and 2017, only 132 were included in this Identification of HPV genotypes using nested PCR assay study due to missing data for some patients. The popula - The HPV genome in the DNA extracted from FFPE sam - tion was aged between 24 and 87 years; the mean age of ples was genotyped using nested PCR followed by ampli- the cohort was 54.9 years (SD ± 12.8 years). The major - con sequencing. The nested PCR used primers derived ity of women were postmenopausal 76.5% (101/132) and from the MY09/MY011 region of the L1 gene of the multiparous 84.6% (77/91) with a maximum of 12 preg- HPV genome and GP5 + /6 + consensus inner primers nancies. Moreover, age at first sexual intercourse varied as described previously [9]. The amplification result was between 10 and 22 years (median = 16 years). Only 35.6% visualized on electrophoresis agarose gels stained with (36/101) had never been to school. Histological analy- ethidium bromide and observed on a UV transillumina- ses showed that 6.82% (9/132) of the patients had ADC, tor. Results were deemed positive based on the presence 12.12% (16/132) had CIN3 and SCC was found in 81.06% of a 150 bp band and the sequenced amplicon corre- (107/132) of included patients (Table 1). The mean age sponding to HPV upon a BLAST analysis. The amplicon of patients with CIN3 was 46.7 years (SD ± 10.1 years), was sequenced performed using the BigDye Terminator 55.1 years (SD ± 12.1 years) for ADC and 56.1 years v3.1 cycle sequencing kit according to the manufacturer’s (SD ± 12.8 years) for SCC. In addition, histological anal- protocol. yses showed that the percentage of tumor cells varied between 5 and 100% depending on the histological diag- nosis of the lesions. For instance, more than 50% of SCCs Identification of HPV genotypes using real‑time PCR had more than 50% tumor cells, but 62.5% of CIN3 cases Real-time PCR was carried out to detect five different had between 5 and 50% tumor cells (Table 2). Clinical HPV genotypes (16, 18, 33, 45 and 58) [13]. Each PCR stage data, available for only 79 of the patients, showed reaction was performed in a 25 ul volume using 50 ng that the III (A&B) and IV (A&B) stages were found in of template DNA in 5 ul, 12.5 ul of Platinum Quantita- 58.2% (46/79) of SCC. In addition, 36.96% (17/46) of tive PCR SuperMix-UDG (Invitrogen), 10 pmol of each patients at these III and IV stages were younger than primer and 5 pmol of each probe. Thermal cycling was 50 years of age (Table 3). based on the following program: an initial denaturation step at 95 °C for 10 min, 55 amplification cycles (dena - Overall prevalence of HPV turation at 95 °C for 15 s, annealing at 50 °C for 20 s and Of the 132 samples investigated in this study, at least one extension at 60 °C for 40 s each). A positive and a nega- HPV was detected in 92.4% (122/132) even if the GAPDH tive control were included in each amplification reaction. Moussavou‑Boundzanga et al. Infectious Agents and Cancer (2023) 18:16 Page 4 of 8 Table 1 Age of cervical cancer patients included in the study according to the histological diagnosis of the lesions (CIN3, ADC, SCC) Age group (years) Cervical intraepithelial neoplasia Adenocarcinoma (ADC) Squamous cell carcinoma Total 3 (CIN3) (SCC) < 39 3 (18.8%) 0 9 (8.4%) 12 (9.09%) 40–49 7 (43.8%) 2 (22.2%) 27 (25.2%) 36 (27.27%) 50–59 5 (31.2%) 5 (55.6%) 37 (34.6%) 47 (35.61%) 60–69 1 (6.2%) 1 (6.2%) 13 (12.1%) 15 (11.36%) > 70 0 1 (11.1%) 21(19.6%) 22 (16.67%) Total 16 (12.1%) 9 (6.8%) 107 (81.1%) 132 (100%) 77% (77/107) of ADC/CIN3 and SCC samples, respec- Table 2 Tumor cell percentages according to histological diagnosis (CIN3, ADC, SCC) tively. The second most frequent high-risk genotype was HPV18 with percentages of 13.3% (2/15) to 28.6% (2/7) Tumor cell percentage in CIN3 and ADC cases, respectively (Table 4) and in [5–40] ]40–50] ]50–80] ]80–100] 15.0% (16/117) of SCCs. However, in 50% and 61.1% of n (%) n (%) n (%) n (%) cases, HPV18 was found in co-infection with HPV16 CIN3 (n = 16) 6 (37.5%) 4 (25%) 3 (18.75%) 3 (18.75%) for ADC/CIN3 and SCC samples, respectively. The per - ADC (n = 8) 2 (25%) 1 (12.5%) 1 (12.5%) 4 (50%) centages of the other high-risk HPV genotypes in SCC SCC (n = 107) 23 (23.5%) 24 (24.5%) 34 (34.7%) 17 (17.3%) varied between 1.1% and 11.7% (HPV35 and HPV58, respectively). Moreover, in 58.3% of cases, these minority genotypes were found in co-infection with either HPV16 or HPV18. Among CIN3 histological diagnostic 2/15 gene was amplified in 67.42% (89/132) samples. How - were found co-infected with HPV16 and HPV18 on an ever, only 64% of the different genotypes were detected hand and HPV45 and HPV58 on an other hand. regard- with two methods used for our virological investiga- ing the ADC histological diagnostic, 3/7 cases were co- tions. Nonetheless, 100% of the HPV genotypes detected infected. It was HPV16-HPV18; HPV16-HPV58 and with qPCR were also detected with conventional nested HPV18-HPV45. PCR (Additional file 1: Table S1). HPV prevalence was 77.8% (7/9), 93.6% (15/16) and 93.5% (100/107) among HPV genotype prevalence in SCC according to age the ADC, CIN3 and SCC samples, respectively. Six dif- All women with SCC were divided into five age groups ferent HPV genotypes (HPV16, 18, 33, 35, 45 and 58), all (26–39; 40–49; 50–59; 60–69 and 70–87). Although classified as high risk, were found in descending order: the overall prevalence of at least one high-risk HPV HPV16 75.4% (92/122); HPV18 18% (22/122); HPV58 was 87.5% (94/107), the prevalence differed accord - 10.7 (13/122); HPV45 9.8% (12/122); HPV33 4.1% (5/122) ing to age group. It varied from 86.7% (13/15) to 90.9% and HPV35 0.8% (1/122). Co-infections were identified in (20/22) for the 60–69 and 70–87 groups, respectively 28/122 cases (23%). HPV16 and HPV18 were both found (Table 5). Moreover, regardless of the age group consid- in 82.8% (101/122) samples. The HPV16 genotype was ered, HPV16 genotype was the most frequent genotype, the most frequent genotype, detected in 60% (15/25) and varying from 61.7% (29/47) to 75% (27/36) for the 50–59 Table 3 Clinical stages of squamous cell carcinoma (SCC) by age group Age group Clinical stages of squamous cell carcinoma IA IB IIA IIB IIIA IIIB IVA IVB Total < 39 1 0 1 0 0 1 2 2 7 40–49 1 1 3 3 0 7 3 2 20 50–59 1 2 2 9 2 7 6 0 29 60–69 1 1 2 0 2 2 1 1 10 > 70 1 1 1 2 0 5 3 0 13 Total 5 5 9 14 4 22 15 5 79 M oussavou‑Boundzanga et al. Infectious Agents and Cancer (2023) 18:16 Page 5 of 8 Table 4 HPV genotype detected according to histological diagnosis of the lesions (CIN3, ADC, SCC) HPV genotype detected Cervical intraepithelial neoplasia 3 Adenocarcinoma (ADC) Squamous (CIN3) cell carcinoma (SCC) n = 16 (%) n = 9 (%) n = 107 (%) All genotypes 15 (93.8%) 7 (77.8%) 100 (93.5%) HPV16 10 (66.7%) 5 (71.4%) 77 (77.0%) HPV18 2 (13.3%) 2 (28.6%) 18 (18.0%) HPV33 1 (6.7%) 0 4 (4.0%) HPV35 0 0 1 (1.0%) HPV45 2 (13.3%) 2 (28.6%) 8 (8.0%) HPV58 1 (6.7%) 1 (14.3%) 11 (11.0%) Table 5 HPV genotype detected according to the age group of squamous cell carcinoma (SCC) patients Age group (years) 26–39 years 40–49 years 50–59 years 60–69 years 70–87 years n (%) 11/12 (91.7%) 33/36 (91.7%) 45/47 (95.7%) 13/15 (86.7%) 20/22 (90.9%) HPV16 11 27 29 9 16 HPV18 2 5 9 3 3 HPV33 0 1 2 1 1 HPV35 0 1 0 0 0 HPV45 0 4 6 1 1 HPV58 0 2 6 1 4 HPV16, 18 2 4 5 1 1 HPV16, 45 0 1 1 1 1 HPV16, 58 0 1 2 1 3 HPV18, 58 0 0 1 0 0 HPV16, 18, 45 0 0 1 0 0 and 41–49 age groups, respectively. Except for HPV16, percentage of HPV detected ranging from 80.9% (17/21) the only other HPV genotype found in several age groups to 93.3% (14/15) for groups IIA-IIB and IVA-IVB, respec- was HPV18, even though it was found in co-infection tively. In addition, in 66.2% (45/58) of the cases, a sin- with HPV16 in 61.1% (11/18) of the cases. The other less gle HPV genotype was detected, albeit varying with age frequent genotypes (HPV33, 45 and 58) were not found group: IA-IB was the group with the most co-infections, in the first age group (26–39). In the other groups, they with only 28.5% of mono-infections; in the IIIA-IIIB were detected either individually in 42.8% (9/21) of cases group, 95% were mono-infections. The HPV16 genotype or in co-infection with HPV16 or 18 or with the another was found in all stage groups and was the most frequent genotype. The HPV33 and 58 genotypes were found indi - regardless of stage group. Moreover, HPV16 was also the vidually between two and four times, respectively, in all genotype most frequently found in mono-infections. In the age groups except for the 60–69 age group. Finally, no contrast, HPV18 was more often found in co-infection age group was statistically more infected than any other, with HPV16 (7/11) than in mono-infection. Finally, the either with HPV overall or with a particular HPV geno- minority genotypes (HPV33, 45 and 58) were found in type (p = 0.8157). mono-infection only in groups IA-IB and IIA-IIB, but in 80% of co-infection cases with HPV16 in the other two HPV genotype prevalence in SCC according to clinical groups IIIA-IIIB and IVA-IVB (Table 6). stage Of the 107 SCCs in this study, histological stage (four Discussion groups, IA-IB, IIA-IIB, IIIA-IIIB and IVA-IVB) could Cervical cancer is the leading cause of cancer-related be established for only 67 SCCs. At least one HPV death among women in sub-Saharan Africa (SSA) was detected in 86.6% (58/67) of the cases, with the but it can be prevented by vaccination. But, due to Moussavou‑Boundzanga et al. Infectious Agents and Cancer (2023) 18:16 Page 6 of 8 Table 6 HPV genotype detected according to the clinical (FIGO) has led to a large deployment of thermal cyclers in hos- stage of SCC pitals in the capital of Gabon as well as in the provinces [16]. Thus, the implementation of molecular screening Clinical stage of SCC n (%) now seems possible throughout the country. To determine the prevalence of the different HPV IA/IB IIA/IIB IIIA/IIIB IVA/IVB N/A genotypes associated with CIN3 + in the Gabonese n = 8 n = 21 n = 23 n = 15 n = 38 population according to methodologies standardized All geno‑ 7 (87.5%) 17 (80.9%) 20 (86.9%) 14 (93.3%) 34 (89.5%) with other French-speaking African countries belong- types ing to the COFAC-Col consortium [7], they were HPV16 2 10 15 8 20 screened on the FFPE samples. The proportions of HPV HPV18 – – 3 – 2 detected were lower than those reported in studies per- HPV33 1 – – – 3 formed on smears or biopsies in the same Gabonese HPV45 – 2 – 1 – population [9–11]. There are two main reasons behind HPV58 – 2 – – 2 this absence of HPV detection in a small proportion HPV59 – – – – 1 of cancer biopsies [17, 18]. First, the DNA extracted HPV16, 18 2 2 – 2 4 from FFPE samples may be partially degraded, mak- HPV16, 45 1 – 1 – – ing HPV detection more difficult for technical reasons. HPV16, 58 1 – 1 2 2 Second,the target region of the PCR/qPCR used may HPV18, 58 – – – 1 – have been deleted during the process of integration of HPV16, 18, – 1 – – – the viral genome into that of the host. A metanalysis reported viral integration of HPV into the host genome in more than 80% of cervical cancers [19]. This propor - tion is similar to that obtained in a recent study per- financial and logistical obstacles, their implementa - formed in Gabon, in which the viral genome was found tion is difficult in SSA. Although current vaccines can integrated in 85.7% of cervical cancer cases [20]. only prevent up to 9 different genotypes, it affords The diversity of HPV genotypes detected in this study cross-protection between the genotypes targeted by is lower than that obtained in other studies conducted the vaccine and non-target genotypes. However, the in other SSA countries. Indeed, only six genotypes effectiveness of these campaigns also depends on a bet - were detected: HPV16, 18, 33, 35, 45 and 58. Previ- ter understanding of the distribution of different HPV ous studies conducted in Gabon reported between 11 genotypes in women with high-grade lesions. Although and 24 different genotypes including the six high-risk many studies have been conducted over the past few genotypes in this study [9–11]. However, these studies decades in SSA countries, their comparison is difficult were based on total DNA extracted from either cervi- because of the lack of standardization in the meth- cal smears or non-paraffin biopsies, in contrast to this odologies used in pathology and virology. Although study where only high-grade tumor tissues were spe- screening by molecular testing for HPV genomic DNA cifically collected from paraffin slides. This preselection is more efficient than screening by cytology, histologi - decreases the probability of finding HPV genotypes cal confirmation of cases remains the cornerstone of not associated with cancer or high-grade lesions. For clinical diagnosis. However, pathology laboratories are example, high-grade CIN is primarily caused by a single rare in low-income countries [15]. For example, to date HPV type [21]. The diversity observed in Gabon is also in Gabon, there are only four laboratories all located in lower than that observed in Senegal (HPV16, 18, 31, the capital city and the most recent of which became 33, 35, 39, 45, 56 and 58) and Cameroon (HPV16, 18, operational in 2020. However, two of these laboratories 33, 35, 39, 45, 51, 56 and 82) in FFPE samples, where located at the CHUA and the HIA OBO have biobanks nine genotypes were detected [22, 23]. Although diver- that can be used to assess the prevalence of different sity varies among SSA countries, the two main geno- HPV genotypes in cervical cancer according to clinical types are still HPV16 and HPV18, with more than 75% stage. However, screening based on smears associated of cases in Gabon. Finally, the clinical data for cervical with cytological analysis has a low coverage rate due to cancer in our study are consistent with previous studies the insufficient infrastructures and the lack of trained conducted in Africa, and particularly in SSA [24, 25]. personne; HPV screening covers a greater proportion of Cervical cancer in Gabon mainly affects young women the population, but is difficult to set up due to the need under 50 years of age and a large number of cervical fo specific infrastructures unavailable on a large scale cancer cases is diagnosed at a late stage, with 87.3% of in Gabon. The global health situation due to COVID-19 patients at stage II or higher. M oussavou‑Boundzanga et al. Infectious Agents and Cancer (2023) 18:16 Page 7 of 8 Competing interests Conclusion The authors have no conflict of interest. This study was part of a transversal initiative between several French-speaking countries to standardize meth- Author details Centre International de Recherches Médicales de Franceville (CIRMF), BP ods to obtain results generalizable across the SSA 69 Franceville, Gabon. Laboratoire de Biologie Moléculaire et Cellulaire region. Our results confirm the high prevalence of the (LABMC), Université des Sciences et Techniques de Masuku, BP 941 France‑ HPV16 and 18 genotypes among high-grade lesions in ville, Gabon. Centre Hospitalier Universitaire de Libreville, Libreville, Gabon. 4 5 Institut de Cancérologie de Libreville (ICL), Libreville, Gabon. I nstitut de the Gabonese population. Among the six genotypes Recherches et de Développement (IRD), MIVEGEC, CNRS, IRD, Université de detected, five are targeted by the HPV 9-valent vaccine. Montpellier, Montpellier, France. Unité Environnement et Risques Infectieux, This result highlights the need for a national strategy Cellule d’Intervention Biologique d’Urgence, Institut Pasteur, Université Paris‑ Cité, 25 Rue du Docteur Roux, 75724 Paris, France. Unit of Discovery for the early screening of precancerous lesions coupled and Molecular Characterization of Pathogens, The Center for Microbes, with a broad national vaccination program targeting Development and Health, Institut Pasteur of Shanghai ‑ Chinese Academy non-sexually active women to significantly reduce the of Sciences, Life Science Research Building, No 320 Yueyang Road, XuHui District, Shanghai, China. long-term cancer burden. Received: 4 July 2022 Accepted: 22 February 2023 Abbreviations HPV Human papillomavirus CIN 3 Cervical intraepithelial neoplasia 3 ADC Adenocarcinoma References SCC Squamous cell carcinoma 1. The L. GLOBOCAN 2018: counting the toll of cancer. Lancet (London, FFPE Formalin‑fixed paraffin‑embedded England). 2018;392(10152):985. 2. WHO: Global Action Plan for the Prevention and Control of NCDs 2013–2020. 2013. Supplementary Information 3. Garland SM, Hernandez‑Avila M, Wheeler CM, Perez G, Harper DM, The online version contains supplementary material available at https:// doi. Leodolter S, Tang GW, Ferris DG, Steben M, Bryan J, et al. Quadrivalent org/ 10. 1186/ s13027‑ 023‑ 00493‑z. vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007;356(19):1928–43. Additional file1. Table S1. HPV genotype detected by histological stage 4. Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter D, Kitch‑ according to molecular method ener H, Castellsague X, Teixeira JC, Skinner SR, et al. Efficacy of human papillomavirus (HPV )‑16/18 AS04‑adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final Acknowledgements analysis of a double‑blind, randomised study in young women. Lancet We acknowledge Carolyn Engel‑ Gautier for editing the English in the (London, England). 2009;374(9686):301–14. manuscript. 5. Qiao YL, Wu T, Li RC, Hu YM, Wei LH, Li CG, Chen W, Huang SJ, Zhao FH, Li MQ, et al. Efficacy, safety, and immunogenicity of an Escherichia coli‑ Author contributions produced bivalent human papillomavirus vaccine: an interim analysis of a NB and IHK conceived and designed the study. PMB performed all the randomized clinical trial. J Natl Cancer Inst. 2020;112(2):145–53. molecular biology assays for HPV genotyping and statistical analysis. JKC and 6. Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, RR carried out all preparations of FFPE blocks and slides for anapathology Dicker DJ, Chimed‑ Orchir O, Dandona R, Global Burden of Disease Cancer analyses. CEA performed all anapathology analyses. All authors analyzed the C, et al. Global, regional, and national cancer incidence, mortality, years of data. PMB and NB wrote the manuscript. CEA and IHK critical reading of the life lost, years lived with disability, and disability‑adjusted life ‑ years for 32 manuscript. All authors read and approved the final manuscript. cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3(4):524–48. Funding 7. Berthet N, Berling C, Nabi H, Woto Gaye G, Toure Kane C, Diop‑Ndiaye This study was supported by National Cancer Institute (INCa) in France H, Koumakpayi IH, Engohan Aloghe C, Bisvigou U, Didi Coulibaly J, et al. (COFAC‑ Col) and by the CIRMF which is supported by the Government of COFAC‑ Col: a cervical cancer control networking initiative in five French‑ Gabon, Total‑Fina‑Elf Gabon, and the Ministère de la Coopération Française. speaking African countries. Cancer Epidemiol Biomark Prev Publ Am The funders had no role in study design, data analysis or preparation of the Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2016;25(6):1004–5. manuscript. 8. Santé Mdl: Plan National de Développement Sanitaire (2019). Accessed 01 Aug 2019. Availability of data and materials 9. Moussavou PB, Koumakpayi IH, Nkili‑Meyong AA, Labouba I, Bisvigou All data are reported in the manuscript. U, Chansi JK, Engohan‑Aloghe C, Dissanami F, Ambounda N, Delannoy‑ Vieillard A‑S, et al. Molecular analysis of human Papillomavirus detected among women positive for cervical lesions by visual inspection with Declarations acetic acid/Lugol’s iodine ( VIA/VILI) in Libreville, Gabon. Infect Agents Cancer. 2016;11(1):50. Ethical approval and consent to participate 10. Zoa Assoumou S, Ndjoyi Mbiguino A, Mabika Mabika B, Nguizi Ogoula This study was performed following the Helsinki Declaration and approved by S, El Mzibri M, Khattabi A, Ennaji MM. Human papillomavirus genotypes the Medical Ethics Committee of Gabon (consent number PROT N°0010/2013/ distribution among Gabonese women with normal cytology and cervical SG/CNE). This study also obtained the authorization of the Scientific Com‑ abnormalities. Infect Agents Cancer. 2016;11:2. mittee of the Centre International de Recherches Médicales de Franceville 11. Zoa‑Assoumou S, Ndjoyi‑Mbiguino A, Mabika BM, Belembaogo E, (CIRMF). Khattabi A, Ennaji MM. Human papillomavirus genotypes distribution in cervical cancer cases in Gabon. Infect Agents Cancer. 2016;11:42. Consent for publication 12. Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma Not applicable. of the cervix. 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Nkili‑Meyong AA, Moussavou‑Boundzanga P, Labouba I, Koumakpayi IH, Jeannot E, Descorps‑Declere S, Sastre ‑ Garau X, Leroy EM, Belembaogo E, Berthet N. Genome‑ wide profiling of human papillomavirus DNA integration in liquid‑based cytology specimens from a Gabonese female population using HPV capture technology. Sci Rep. 2019;9(1):1504. 21. Quint W, Jenkins D, Molijn A, Struijk L, van de Sandt M, Doorbar J, Mols J, Van Hoof C, Hardt K, Struyf F, et al. One virus, one lesion–individual components of CIN lesions contain a specific HPV type. J Pathol. 2012;227(1):62–71. 22. Pirek D, Petignat P, Vassilakos P, Gourmaud J, Pache JC, Rubbia‑Brandt L, Sando Z, McKee TA, Ho L. Human papillomavirus genotype distribution among Cameroonian women with invasive cervical cancer: a retrospec‑ tive study. Sex Transm Infect. 2015;91(6):440–4. 23. Diop‑Ndiaye H, Sastre ‑ Garau X, Drame A, Dembele B, Ba NN, Diop‑ Diongue O, Mbow M, Diakhaby MEB, Woto‑ Gaye G, Toure Kane C, et al. Respective prevalence of high‑risk HPVgenotypes in cervical neoplasia in Senegal. J Med Virol. 2021;93(8):5110–7. 24. Maranga IO, Hampson L, Oliver AW, Gamal A, Gichangi P, Opiyo A, Holland CM, Hampson IN. Analysis of factors contributing to the low survival of cervical cancer patients undergoing radiotherapy in Kenya. PLoS ONE. 2013;8(10): e78411. 25. Parkin DM, Bray F. Chapter 2: the burden of HPV‑related cancers. Vaccine. 2006;24(Suppl 3):11–25. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in pub‑ lished maps and institutional affiliations. Re Read ady y to to submit y submit your our re researc search h ? Choose BMC and benefit fr ? 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Journal
Infectious Agents and Cancer – Springer Journals
Published: Mar 8, 2023
Keywords: High-grade cervical lesions; Invasive cervical cancer; HPV; Gabon