Molecular Epidemiology of High-Risk Human Papillomavirus Infection in Burkina Faso

*Théodora Mahoukèdè Zohoncon, Rogomenoma Alice Ouedraogo, Florencia Wendkuuni Djigma, Lassina Traore, Teega-Wendé Clarisse Ouedraogo, Maimouna Ilboudo, Regine Ilboudo, Catherine Salambanga, Sindimalgdé Patricia Guigma, Sessi Frida Tovo, Mah Alima Esther Traore, Prosper Bado, Ali Kande, Cyrille Bisseye, Abdoul Karim Ouattara, Ina Marie Angèle Traore, Djeneba Ouermi, Tani Sagna, Albert Théophane Yonli, Wendyam Marie Christelle Nadembega, Dorcas Obiri-Yeboah, Yvette Marie Chantal Gyebre, Olga Mélanie Lompo, Charlemagne Marie Ragnag-Newende Ouedraogo and Jacques Simpore*

## **Abstract**

The aim of the present study was to determine the distribution of high-risk human papillomavirus (HR-HPV) genotypes in childbearing age women, teenage girls, HIV-infected women, women with high-grade precancerous lesions and cervical cancer, sex workers, men, and otolaryngology tumor cases in Burkina Faso. This descriptive cross-sectional study with several target groups, consisted of 2386 samples from Burkina Faso. HR-HPV genotypes were characterized using real-time multiplex PCR. The prevalence of HR-HPV ranged from 15.63 to 72.31% depending on the target population and the nature of the samples. The most predominant genotypes in descending order were HPV-56, HPV-52, HPV-39, HPV-59, HPV-51, HPV-35, HPV-31, HPV-18, HPV-68, HPV-16, HPV-66, HPV-58, HPV-45, and HPV-33. The results of the present study show a wide variation in the distribution of HR-HPV genotypes in Burkina Faso. Genotypes 16 and 18 covered by HPV vaccines only accounted for 32.23% of HR-HPV cases.

**Keywords:** HPV, genotypes, cervical cancer, ENT cancer, Burkina Faso

## **1. Introduction**

Virus-induced cancers represent a huge burden, especially in developing countries. According to recent estimates from the International Agency for Research on Cancer (IARC), 16% of new cases of cancer worldwide are attributable to infections, of which 11% are viral infections. In sub-Saharan Africa, one-third of all cancers are infection-induced cancers [1]. Human papillomaviruses are small non-enveloped viruses (about 55 nm in diameter) of the Papillomaviridae family with a compact structure and a small circular genome (8000 base pairs), encoding 8–9 proteins depending on the genotype (LCR, L1, L2, E1, E2, E4, E5, E6, and E7) [2]. E5, E6, and E7 proteins are involved in cell proliferation and transformation [3, 4]. It is noteworthy that persistent infection with high oncogenic risk human papillomavirus (HR-HPV) can lead to precancerous lesions, which generally begin with slight modification (CIN 1), that can progress to more severe lesions such as CIN 2 then CIN 3 (carcinoma *in situ*). These lesions can regress spontaneously or progress to cancer. HR-HPV infection is recognized as the major risk factor associated with cervix, penis, vulva, vagina, anus, and oropharynx cancers [5]. Globally, cervical cancer remains one of the leading causes of morbidity and mortality with about 569,847 cases and 311,365 deaths occurring in 2018 [6]. Low-income countries have the highest incidence, especially sub-Saharan Africa, where it is the second most common female malignancy [7] and the leading cause of cancer death in women [8].

In West Africa, the annual estimate of cervical cancer burden is 31,955 cases and 23,529 deaths [9]. However, most sexually active men and women can be infected with HR-HPV at some point in their lives, and persistent infection could lead to precancerous lesions and progress into invasive cancer [1, 5]. In addition, HPV infection can affect fertility in men [10, 11]. According to the World Health Organization (WHO), men genital infections with any type of HPV are estimated at least at 19.1% in sub-Saharan Africa [12].

In Burkina Faso, cervical cancer is the most commonly diagnosed cancer with an estimated incidence of 2517 cases and 2081 deaths per year [13]. In addition, otolaryngology and cervico-facial cancers are relatively frequent and account for 24.5% of this entity [14]. Gynecological cancers associated with persistent HR-HPV infection, therefore, threaten many African communities and economies, upsetting the trends of positive societal development. Although HR-HPV is the main causative agent of cervical cancer, other important cofactors (environmental or genetic) such as gene polymorphisms (E6, E7, MMP1, MMP3, TNF-alfa, and IL-18) are involved in the clearance and pathway of carcinogenesis [15].

HIV infection is an additional risk factor [16, 17] as well as some risky behaviors such as multiple sexual partners, especially among sex workers, leading to higher rates of cervical cancer [18] and increasing the risk of penile cancer in men [19]. Nevertheless, preventive measures through behavior modification, screening, and vaccination can significantly control these viral-induced cancers. To efficiently combat this pathology, it is, therefore, necessary to investigate whether the HR-HPV genotypes found in our populations, especially the most common in cancers cases, are covered by the available vaccines. To address this concern, the objective of the present study was to determine the distribution of HR-HPV genotypes in a general population including childbearing age women, teenage girls, HIV-infected women, women with high-grade precancerous lesions and invasive cervical cancer, sex workers, men, and histologically confirmed otolaryngology tumor (ear, nose, and throat) in Burkina Faso.

## **2. Material and methods**

## **2.1 Type and study population, sample collection**

From 2013 to 2017, we carried out a large-scale, descriptive cross-sectional, and multicenter epidemiological study in Burkina Faso along with the retrospective data collection and analysis. The population of the present study consisted of 2386 participants, including eight (8) target groups: childbearing age women, teenage girls, HIV-infected women, sex workers, men, women with high-grade precancerous lesions (CIN 2/3), tissue from invasive cervical cancer, and histologically confirmed otolaryngology tumor (ear, nose, and throat cancers) in Burkina Faso.

The study was conducted in two phases: a descriptive cross-sectional study with 2025 participants made up of 1321 childbearing age women, 200 teenage girls, 183 HIVinfected women, 200 sex workers, and 124 men. We first focused on awareness-raising of HPV infection prevention and the risk of developing cervical cancer at several sites.

The goal after awareness-raising was to include in the target groups, all sexually active women (SAW) regardless of age who were not pregnant and provided informed consent to participate in the study. The exclusion was being in the menstruation period, during the study recruitment, and have had a total hysterectomy.

Prior to the samples collection, socio-demographic data, sexual behavior, HIV serology, level of knowledge about HPV and cervical cancer as well as associated diseases were collected using a standardized questionnaire. An individual collection card was used to collect clinical data of each sex worker in the study population. The privacy and confidentiality were respected through the generation of a unique code for each participant.

Midwives and gynecologists using a single-use speculum and sterile swab performed endocervical samples collection at the squamocolumnar junction. The following samples were taken:


Ouagadougou, 535 in the Hauts-Bassins region (Bobo and Orodara), and 266 in the Center-East region (Tenkodogo and Garango);

• from June to August 2017, 200 endocervical samples from sex workers aged 16–50 years were enrolled in Ouagadougou.

The samples thus collected were frozen in a transport medium at −20°C except those from HIV+ women, which were stored at −80°C. The samples were then sent to the CERBA/LABIOGENE molecular biology and genetics laboratory for molecular biology analyzes. Following sampling in women, screening for precancerous lesions was performed using visual inspection of the cervix with acetic acid (VIA) or with Lugol's iodine (VILI).

The second phase, a cross-sectional study with retrospective data collection, involved 358 samples. Using patients medical register available at the Department of Anatomy and Cytopathology of YalgadoOuedraogo University Hospital Center (CHU-YO), 118 cervical tissue specimens were selected based on high-grade (CIN 2/3) intraepithelial lesions diagnosis between February 2009 and May 2015 along with 112 cervical tissue specimens dated from 2009 to 2015 with a histological diagnosis of invasive cervical cancer.

According to the same protocol, we also included 128 histologically confirmed otolaryngology cancerous tissues dated from 2007 to 2017 in four health centers of Ouagadougou, CHU-YO, Shiphra, Sandof, and Philadelphia clinics. All these biopsy specimens were fixed in formalin and embedded in paraffin.

## **2.2 Extraction of HR-HPV viral DNA from endocervical samples**

HR-HPV viral DNA was extracted using the DNA-Sorb-A kit (Sacace Biotechnologies, Como, Italy) from endocervical and sperm samples following the protocol provided by the manufacturer. Endocervical samples of HIV-positive women, DNA was extracted using bio solutions "INSTANT Virus DNA Kit" Analytkjena® (Italy). The extracted DNA was then quantified using UV spectrophotometry at 260 nm and stored at −20°C until PCR amplification.

## **2.3 Samples deparaffinization and extraction of HR-HPV viral DNA from tissue specimens**

In the cytopathology anatomy laboratory of the CHU-YO, the paraffin blocks containing a piece of biopsy were cut with a microtome to obtain five sections of about 20 μm thick. Tissues thus collected in sterile Eppendorf tubes were sent to the CERBA/LABIOGENE for molecular analyzes. DNA extraction was performed using the FFPE DNA Purification Kit, following the protocol provided by the manufacturer.

#### **2.4 Spermogram and spermocytogram**

Each semen sample was assessed according to the following parameters: volume, motility, concentration, morphology, and vitality of spermatozoa, using an optical microscope.

## **2.5 Molecular characterization of HR-HPV genotypes using real-time multiplex PCR**

Extracted DNA was amplified with "HPV Genotypes 14 Real-TM Quant" kit (Sacace Biotechnologies, Como, Italy) using Sacycler-96 Real-time PCR v.7.3

*Molecular Epidemiology of High-Risk Human Papillomavirus Infection in Burkina Faso DOI: http://dx.doi.org/10.5772/intechopen.102327*

(SACACE Biotechnologies®). Fourteen HR-HPV genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) could be detected in a multiplex PCR procedure with β-globin gene as internal control.

Two different techniques were used to amplify the viral DNA extracted from samples of HIV+ women: PCR/Hybridization for the detection of HPV 6, 11, 16, 18, 45, 30'S and 50'S using the "HPV Blot STAR" kit from Diatech® (Italy), without discrimination of the HPV 30'S and 50'S genotypes, respectively. The second technique using the "HPV High-Risk Typing Real-TM" kit (SACACE biotechnologies®, Italy) allows specific detection of the following high-risk genotypes: 16, 18, 31, 39, 45, 59, 33, 35, 56, 51, 52, and 58. The amplification program was as follows: 1 cycle of 95°C for 15 minutes; 5 cycles of 95°C for 05 s, 60°C for 20s, 72°C for 15 s; 40 cycles of 95°C for 05 s, 60°C for 30s, and 72°C for 15 s.

#### **2.6 Ethical considerations**

Each phase of the present study received the approval of the Ethics Committee for Health Research of Burkina Faso (CERS) (n °2009-009/CR/135 of April 22, 2009 (HIV+); N2014-8-099 of August 6, 2014 (CIN2/3); Deliberation No. 2016- 2102-0012 of 02/03/2016 (general population); No.2017-1026/MS/RCEN/DRSC (sex workers); No. 2014-8-099 (ICC); Ref.2017/CERBA/II-24/0019 of 24-02-2017 (otolaryngology samples) along with approbation of the regional health directorates (DRS) of the various target collection sites. Free and informed consent, anonymity, and confidentiality were strictly observed.

#### **2.7 Statistical analyzes**

Statistical analysis of data was performed using IBM SPSS 21 and Epi Info v7.0 software. The Chi-square test was used for comparisons with a significant difference for *p* < 0.05.

## **3. Results**

#### **3.1 Mean age of target groups in our study population**

The present study focused on eight (8) target groups, including childbearing age women, adolescent girls, HIV-infected women, sex workers, men, high-grade precancerous lesions (CIN 2/3) cases, invasive cervical cancer, and histologically confirmed otolaryngology tumors in Burkina Faso. The mean age ranged from 18.7 ± 0.7 to 46.32 ± 12.76 years (**Table 1**).


**Table 1.**

*Mean age of target groups in the study population.*

## **3.2 Socio-demographic data and sexual behavior of the study population women**

The general female population of the present study consisted of 1321 childbearing age women and 200 adolescent girls. Among them, only 142 (9.34%) had a university education while 951 (62.53%) were living with a partner. Most of them (61.34%) were over 18 years of age at first, and 43.19% never used a condom during sex. It is noteworthy that 40.89% of them had a history of STIs and 50.43% declared to be using contraception. Screening for precancerous lesions using VIA/VILI revealed 70 positive women (**Table 2**).

## **3.3 HR-HPV prevalence**

The beta-globin gene used as an internal control was an essential factor for results validation in multiplex real-time PCR procedures for HR-HPV genotypes detection. Out of 118 CIN 2/3 tissue blocks samples, 43 positives for the beta-globin gene were considered valid while 65 samples were valid out of the 112 ICC specimens. Only valid samples were considered for the present study. HPV data were therefore available for 2264 valid samples out of 2386 recruited participants.

The prevalence of HR-HPV ranged from 15.63% to 72.31% based on the target population and nature of the samples. The overall prevalence was estimated at


#### **Table 2.**

*Sociodemographic data and sexual behavior of the women general population.*

#### *Molecular Epidemiology of High-Risk Human Papillomavirus Infection in Burkina Faso DOI: http://dx.doi.org/10.5772/intechopen.102327*

39.05% (824/2264). As shown in **Figure 1**, a prevalence of 72.31% (*n* = 47) was observed in ICC cases, 63.90% (*n* = 117) in HIV-positive women, 53% (*n* = 106) in sex workers women, 48.80% (*n* = 21) in CIN 2/3 cases, 41.50% (*n* = 83) in adolescent girls, 35.40% (*n* = 468) in childbearing age women, 17.74% (n = 22) in men and 15.63% (*n* = 20) in otolaryngology cancers.

#### **3.4 Prevalence and genotypic distribution of HR-HPV in target groups**

The amplification kits used enabled us to essentially characterize the HR-HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68. **Table 3** shows the distribution of HR-HPV in descending order in the study population. Overall, varied distribution of HR-HPV genotypes was observed with predominance of non-HPV 16 and 18 genotypes (**Table 3**).

On the one hand, HPV 16 was particularly absent in childbearing age women from the Haut-Bassins region, in southwestern Burkina Faso, and in women with high-grade precancerous lesions (**Table 3**). On the other hand, HPV 18 was most common in ICC cases and HIV-positive women. In addition, HPV 56 was predominant in childbearing age women, otolaryngology cancers, and men. However, a predominance of HPV 68 was registered in sex workers and absent in ICC and otolaryngology cancers. It is noteworthy that HPV 56 was predominant in the general population as well as in the target groups (**Table 3**).

**Table 4** shows the HR-HPV genotypes detected in the present study population and their prevalence in each target population. Considering the five most common HR-HPV genotypes found in the different target groups, HPV 16 presented a low proportion, especially in childbearing age women (1.82%), adolescent girls (5.2%), sex workers (2.7%), HIV + (4.9%), CIN 2/3 (0.0%). However, in decreasing order of frequency, it was the third genotype identified in otolaryngology cancers, the fourth in ICC, and the fifth in men. In HIV-positive women, a frequency of 2% of HPV6 infection was observed.

#### **3.5 Prevalence of single and multiple infections in target groups**

PCR screening in each target group revealed that among the 884 cases of HR-HPV infections, the number of genotypes per infected person ranged from 1 to 9 out of 14 genotypes tested. Single infection (isolated infection) ranged from 37.61 to 90.50% while multiple infection varied from 9.50 to 62.39% (**Table 5**).

**Figure 1.**

*Prevalence of HR-HPV according to the target groups and nature of the samples in the study population.*


*NB: The general population consists of childbearing age women, adolescent girls, and men. The target population consists of sex workers, HIV+ women, CIN 2/3 cases, ICC cases, and otolaryngology cancers.*

#### **Table 3.**

*Genotypic distribution of HR-HPV in target groups.*

## **3.6 Prevalence of HR-HPV genotypes targeted by bivalent, quadrivalent, and nonavalent HPV vaccines**

The HR-HPV genotypes targeted by bivalent/quadrivalent HPV vaccines (HPV6/11/16/18) were identified in 7.83% of childbearing age women, 10.40% of adolescent girls, 8.90% of sex workers, 25.70% of HIV+ women, 4.30% of CIN 2/3, 38.57% of ICC cases, 14% of men, and 50% of otolaryngology cancer cases. The genotypes covered by the nonavalent vaccine (HPV6/11/16/18/31/33/45/52/58) were 36.22, 43.40, 44.90, 65.30, 39, 75.71, and 40%, respectively in childbearing


#### *Molecular Epidemiology of High-Risk Human Papillomavirus Infection in Burkina Faso DOI: http://dx.doi.org/10.5772/intechopen.102327*


**Table 4.** *Prevalence of HR-HPV in risk population, precancerous lesions, and cancer cases.*


**Table 5.**

*Prevalence of single and multiple infections in target groups.*

## *Molecular Epidemiology of High-Risk Human Papillomavirus Infection in Burkina Faso DOI: http://dx.doi.org/10.5772/intechopen.102327*

**Figure 2.**

*Prevalence of HR-HPV identified in the target groups of our study according to their coverage by available vaccines.*

age women, adolescent girls, sex workers, HIV-positive women, CIN 2/3, ICC, men, and otolaryngology cancer. HR-HPV not covered by bivalent, quadrivalent, or nonavalent HPV vaccines were observed with a higher prevalence in childbearing age women (63.18%), CIN 2/3 cases (61%), and men (60%) (**Figure 2**).

## **4. Discussion**

HPV is one of the carcinogenic viruses, sexually transmitted, widespread in the world with a high prevalence in developing countries especially in Sub-Saharan Africa where socio-cultural and behavioral factors which promote transmission prevail in several regions. In the present epidemiological study, including 2386 samples out of which 2264 were valid using the PCR technique, the overall prevalence of HR-HPV was 39.05% (824/2264). This prevalence is in line with those reported in previous studies supporting a global prevalence of 10.4% of HR-HPV infection [20] which can reach 36.5% in some developing countries [21, 22].

Epidemiological studies suggested a difference in the prevalence and distribution of HR-HPV genotypes in infected women according to regions and risk groups throughout the world [23, 24]. Our results support this variable prevalence and distribution of HR-HPV according to target populations and sample types.

Indeed, the prevalence of 35.40% of infection observed in the population of childbearing age women was lower than that reported in some studies from Tanzania (74%) [25] and Ethiopia (83.2%) [26] almost similar to that of a study conducted in England (35%) [27].

HR-HPV is the main etiologic agent responsible for ano-genital cancers including ICC and a prevalence of 100% could be expected in ICC cases. The high prevalence of 72.31% of HR-HPV infection in ICC cases found in this study was lower than the 100% reported in Gabon [28], 90,7% in Nigeria [29], and 83,2% in Malaysia [30]. The difference in the methodologies used could support the existence of falsenegative samples as reported in a previous study by Tan et al. [30] in Malaysia.

#### *Molecular Epidemiology of High-Risk Human Papillomavirus Infection in Burkina Faso DOI: http://dx.doi.org/10.5772/intechopen.102327*

Furthermore, sex workers and men, an important active group for the maintenance of HPV in the population, showed a high prevalence of HR-HPV in our study. For instance, some studies reported a significant association between HPV infection, high number of sexual partners, and history of STIs [31]. The prevalence of 53% found among sex workers in our study was higher than those of 51.5% and 26% reported respectively in Côte d'Ivoire [32] and Ghana [7]. In contrast, the infection rate of 17.74% in the men of our study population was lower than the 32.4% observed by Zhu et al. [33] in men with genital warts. These results support the fact that sex workers and men constitute a reservoir for the transmission of HR-HPV, hence the importance of awareness-raising among these risk populations about the screening for HPV infection.

Data analysis also showed that 48.80% (21/43) of women with high-grade precancerous lesions (CIN2/3) were infected with HR-HPV; a lower prevalence than the 91.9% reported in another study in a similar population [34]. These results could be explained by the higher rate of infection in women under 30 years old, especially in those of 25–29 and 60 years and over [35–37]. For instance, the mean age of women with CIN 2/3 in our study was 41.5 ± 9.8 years (22–74 years) against was 45.7 years in the study of Wang et al. (21–83 years old).

Several studies reported a high prevalence of HPV infection in HIV+ women [7, 38] as HIV is a well-known factor associated with an increased risk of HR-HPV persistence and multiple infections, and therefore, promote the occurrence of anogenital cancers. The prevalence of 63.90% of HR-HPV observed in this target group of the present study was similar to 65.5% in Ghana [39] but higher than the 36% reported in Nigeria [40] and 33.3% in Brazil [41]. Compared to non-HIV infected women in the general population, this high prevalence could be explained by the immunosuppression and confirm the role of HIV infection as an additional risk factor for the persistence of HR-HPV.

The infection rate of 41.5% found in adolescent girls was lower than the 66.7% observed in South Africa [32]. The difference in age range (15 to 19 years in our study versus 16 to 22 in the South African study) could explain the prevalence variation between the two studies especially when previous studies support that HR-HPV infection is higher in those less than 30 years of age [37].

In our study, HPV 56 was the most common genotype in childbearing age women, men, and otolaryngology cancers with predominance in the general population as well as target groups. This genotype is not covered by any available HPV vaccine, although it has been found in ICC and CIN 2/3 cases [29]. The same is true for HPV 68 which was the most common genotype in sex workers and the fourth common in men.

Since sexual transmission is possible between men and women, the presence of these genotypes in ICC and CIN 2/3 cases suggests a low clearance of the latter HR-HPV genotype in Burkina Faso.

HPV 18 was more common in HIV-positive women and ICC cases with a high frequency of 18.8 and 25.71% respectively. It was also present in CIN 2/3 up to 4.3 and 10% in otolaryngology cancers. Our results are in line with those of studies reporting that this persistent genotype is one of the most commonly found in cervical cancers [29].

Immunodeficiency of HIV-infected women coinfected with HPV 18 promotes high-grade precancerous lesions and the occurrence of invasive cancer of the cervix. It would therefore be necessary to strengthen surveillance through screening, treatment, and vaccination of HIV-infected women.

In addition, unlike studies reporting HPV 16 as the most common genotype throughout the world, especially in cervical cancers [13, 28, 30, 42, 43], this genotype was classified among the less frequent HPVs in our study. However, in ICC

(12.86%), otolaryngology cancers (10%), and in men (8%), HPV 16 was not one of the most common genotypes but reached a frequency that required attention. The low prevalence of HPV-16/18 in our 2386 samples remains an enigma to be elucidated. It remains true that not only the distribution of the HPV genotypes would vary according to the continents, the zones, the countries, and the target populations but also the clearance and the borrowing of the pathway of the carcinogenesis induced by these viruses is modulated by genetic polymorphisms of their human hosts [44, 45]. Evidence from the literature support that the HPV16/18/31/33/35/45/52/58 genotypes are the most common genotypes found in 20% of cervical cancer cases worldwide [24].

The results of the present study also revealed a high prevalence of HR-HPV genotypes covered by the nonavalent vaccine (36.22–75.71%) as well as genotypes of HPV not covered by the vaccine (24.29–63,18%). It is noteworthy that some of the genotypes not covered by vaccine were found in high-grade precancerous lesions and cervical cancer cases [29, 46].

For effective prophylactic actions to control HPV infection, the present epidemiological study in Burkina Faso shows variable distribution of HR-HPV genotypes in the different target populations. Our results suggest that implementation of the nonavalent vaccine is important for HR-HPV infection control in Burkina Faso. Promotion of screening of men, especially for penile cancer and genital warts, and young boys vaccination programs are required since men are well-known reservoirs for HR-HPV dissemination.

## **5. Conclusion**

The studies carried out in Burkina Faso show the circulation of fourteen highrisk HPV genotypes among different layers of the population. The prevalence of HPV infection and genotypes distribution varied among target groups with an overall predominance of non-HPV 16 and 18 genotypes. Moreover, the high-risk HPV genotypes found in Burkina Faso are not all covered by the available vaccines. It is however crucial and important to focus on vaccination using available and accessible vaccines for developing countries to reduce the disease incidence. Cervical cancer and other HPV-induced cancers remain a global public health concern. Strengthening the implementation of primary, secondary, and tertiary prevention strategies incorporating information-education-communication and awarenessraising, will allow effective control of HPV infection and its consequences in men and women.

*Molecular Epidemiology of High-Risk Human Papillomavirus Infection in Burkina Faso DOI: http://dx.doi.org/10.5772/intechopen.102327*

## **Author details**

Théodora Mahoukèdè Zohoncon1,2,3, Rogomenoma Alice Ouedraogo1,2, Florencia Wendkuuni Djigma1,2, Lassina Traore1,2, Teega-Wendé Clarisse Ouedraogo1,2, Maimouna Ilboudo1,2, Regine Ilboudo1,2, Catherine Salambanga1,2, Sindimalgdé Patricia Guigma2 , Sessi Frida Tovo1,2, Mah Alima Esther Traore1,2, Prosper Bado1,2, Ali Kande1,2, Cyrille Bisseye2 , Abdoul Karim Ouattara1,2, Ina Marie Angèle Traore1,2, Djeneba Ouermi1,2, Tani Sagna1,2, Albert Théophane Yonli1,2, Wendyam Marie Christelle Nadembega1,2, Dorcas Obiri-Yeboah4 , Yvette Marie Chantal Gyebre5 , Olga Mélanie Lompo5 , Charlemagne Marie Ragnag-Newende Ouedraogo6 and Jacques Simpore1,2\*

1 Laboratory of Molecular Biology and Genetics (LABIOGENE), Joseph KI-ZERBO University, Burkina, Faso

2 Pietro Annigoni Biomolecular Research Centre (CERBA), Burkina Faso

3 Faculty of Medicine, University Saint Thomas d'Aquin, Burkina Faso

4 Department of Microbiology and Immunology, University of Cape Coast, School of Medical Sciences, University Post Office, Accra, Ghana

5 Yalgado Ouedraogo University Hospital (CHU/YO), Burkina Faso

6 Obstetrician-Gynecologist, UFR/SDS, Joseph KI-ZERBO University, Burkina Faso

\*Address all correspondence to: simpore93@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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*Molecular Epidemiology of High-Risk Human Papillomavirus Infection in Burkina Faso DOI: http://dx.doi.org/10.5772/intechopen.102327*

[14] Ilboudo M, Zohoncon TM, Traore EMA, Traore IMA, Kande A, Djigma FW, et al. Characterization of high-risk oncogenic human papillomavirus genotypes in histologically confirmed ear, nose and throat (Ent) cancers in Burkina Faso. Asian Pacific Journal of Cancer Prevention. 2019;**20**(11):3429-3435

[15] Traore IMA, Zohoncon TM, Djigma FW, Compaore TR, Traore Y, Simpore J. Association of TNF-α-308G/a and IL-18 polymorphisms with risk of HPV infection among sexually active women in Burkina Faso. Biomolecular Concepts. 2020;**11**(1):97-101

[16] Sagna T, Djigma F, Zeba M, Bisseye C, Karou SD, Ouermi D, et al. Human papillomaviruses prevalence and genital co-infections in HIVseropositive women in Ouagadougou (Burkina Faso). Pakistan Journal of Biological Sciences. 2010;**13**(19): 951-955

[17] Yamada R, Sasagawa T, Kirumbi LW, Kingoro A, Karanja DK, Kiptoo M, et al. Human papillomavirus infection and cervical abnormalities in Nairobi, Kenya, an area with a high prevalence of human immunodeficiency virus infection. Journal of Medical Virology. 2008;**80**(5):847-855

[18] Soohoo M, Blas M, Byraiah G, Carcamo C, Brown B. Cervical HPV infection in female sex workers: A global perspective. The Open AIDS Journal. 2013;**7**:58

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[20] De Sanjosé S, Diaz M, Castellsagué X, Clifford G, Bruni L, Muñoz N, et al. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: A meta-analysis. The Lancet Infectious Diseases. 2007;**7**(7):453-459

[21] Ouedraogo RA, Zohoncon TM, Guigma SP, Angèle Traore IM, Ouattara AK, Ouedraogo M, et al. Oncogenic human papillomavirus infection and genotypes characterization among sexually active women in Tenkodogo at Burkina Faso, West Africa. Papillomavirus Research. 2018;**6**:22-26

[22] Bao Y-P, Li N, Smith J, Qiao Y-L. Human papillomavirus type distribution in women from Asia: A meta-analysis. International Journal of Gynecologic Cancer. 2008;**18**(1):71-79. DOI: 10.1111/ j.1525-1438.2007.00959.x

[23] Zohoncon TM, Djigma WF, Ouattara AK, Traore IM, Ouedraogo RA, Traore EM, et al. Mapping of fourteen high-risk human papillomavirus genotypes by molecular detection in sexually active women in the West African sub-region. International Journal of Genetics and Molecular Biology. 2020; **12**(1):11-21

[24] Clifford GM, Smith JS, Plummer M, Munoz N, Franceschi S. Human papillomavirus types in invasive cervical cancer worldwide: A meta-analysis. British Journal of Cancer. 2003;**88**(1): 63-73

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[26] Wolday D, Derese M,

Gebressellassie S, Tsegaye B, Ergete W, Gebrehiwot Y, et al. HPV genotype distribution among women with normal and abnormal cervical cytology presenting in a tertiary gynecology referral Clinic in Ethiopia. Infectious Agents and Cancer. 2018;**13**:28

[27] Howell-Jones R, Bailey A, Beddows S, Sargent A, de Silva N, Wilson G, et al. Multi-site study of HPV type-specific prevalence in women with cervical cancer, intraepithelial neoplasia and normal cytology, in England. British Journal of Cancer. 2010;**103**(2):209-216

[28] Zoa-Assoumou S, Ndjoyi-Mbiguino A, Mabika BM, Belembaogo E, Khattabi A, Ennaji MM. Human papillomavirus genotypes distribution in cervical cancer cases in Gabon. Infectious Agents and Cancer. 2016;**11**(1):1-5

[29] Okolo C, Franceschi S, Adewole I, Thomas JO, Follen M, Snijders PJ, et al. Human papillomavirus infection in women with and without cervical cancer in Ibadan, Nigeria. Infectious Agents and Cancer. 2010;**5**(1):1-4

[30] Tan SC, Ismail MP, Duski DR, Othman NH, Ankathil R. Prevalence and type distribution of human papillomavirus (HPV) in Malaysian women with and without cervical cancer: An updated estimate. Bioscience Reports. 2018;**38**(2):BSR20171268

[31] Mbulawa ZZ, Van Schalkwyk C, Hu N-C, Meiring TL, Barnabas S, Dabee S, et al. High human papillomavirus (HPV) prevalence in south African adolescents and young women encourages expanded HPV vaccination campaigns. PLoS One. 2018;**13**(1):e0190166

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[39] Obiri-Yeboah D, Akakpo PK, Mutocheluh M, Adjei-Danso E, Allornuvor G, Amoako-Sakyi D, et al. Epidemiology of cervical human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) among a cohort of HIV-infected and uninfected Ghanaian women. BMC Cancer. 2017;**17**(1):688

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## **Chapter 9**

Perspective Chapter: Cervical Cancer Elimination by 2030—The W.H.O Goal: Neo Challenges and Next Gen Solutions "TIT for TAT"—The Community Competency Model of Raj ©

*Rajamanickam Rajkumar*

## **Abstract**

Cervical Cancer is the fourth most common cancer among women, worldwide. It accounts for 600,000 new cases per year, and 340,000 deaths globally (WHO 2020 data). It causes a lot of maladies and suffering for women, in the age group of 30–60 years, especially in the poor community of developing countries. Cervical cancer is a great public health problem and is a cause of grave concern for the health system in Low-Middle-Income Countries—LMIC. But cervical cancer is amenable for early detection and successful treatment of precancer stages. Human Papilloma Virus—HPV vaccines offer a high level of primordial prevention, against cervical cancer. Therefore, the World Health Organization, in 2018, has called for "Elimination of Cervical Cancer by 2030." The objective is to reduce the incidence rate of cervical cancer to below 4/100,000, by the year 2030. This leads to many "Neo Challenges" and also opens the door for "Next Gen Solutions". The author, with vast experiences in his Cervical Cancer Screening Projects of IARC/ WHO, at Tamil Nadu, India, during 2000–2007, advocates a strategy called "TIT for TAT—The Community Competency model of Raj©."

**Keywords:** cervical cancer screening, pre cancer treatment, HPV vaccination, elimination

## **1. Introduction**

Cervical Cancer accounts for about 600,000 incident cases and 340,000 cause specific deaths, per year, worldwide, according to IARC/WHO, for the year 2020 [1]

Cervical Cancer ranks 7th among the most common cancers in general and among women, it is ranking as the 4th highest, worldwide, as per the data available with the WHO, for the year 2020 [2].

As far as Mortality is concerned, it is the 9th most common cancer-causing deaths among all cancers and the 4th leading among cancers in women, during 2020 [3].

## **2. Methodology**

## **2.1 Efforts towards elimination of cervical cancer: the favorable features of the disease**

The Human Papilloma Virus—HPV, is the known causal factor for the Cervical Cancer. HPV consists of more than 180 strains. But only a few are oncogenic. The HPV 16, 18 are the high-risk oncogenic strains. When a woman enters sexual life, she is exposed to the HPV infections. But these infections undergo self-clearance, due to the good immunity that may exist in the woman. In some cases, the HPV infection persists for a long time, even up to 10 years. If there are oncogenic strains like the HPV 16, 18, the cervical cells undergo a pathological process called dysplasia or Cervical Intra epithelial Neoplasia—CIN. These are the Pre cancer lesions. At this stage, the disease is detectable by the application of screening tests.

The screening tests which are available:


These tests have acceptable levels of Sensitivity and Specificity to detect CIN lesions.

### **2.2 Precancer lesions: diagnosis and management protocols**

## *2.2.1 See & treat*

The Health care provider, who does the screening, subjects the woman to VIA testing. If the VIA test is positive, then the woman is treated by Cryotherapy/Thermal ablation/Cold coagulation/Laser/Cold knife conization/LEEP or LLETZ.

### *2.2.2 See: test & treat*

The woman is subjected to VIA testing. If the result is positive, another screening test is applied, by means of Pap smear or HPV testing. Even if one of these tests is positive, the woman undergoes Precancer treatment, by modalities listed above.

#### **2.3 The 3 eligibility criteria for elimination, are fulfilled by cervical cancer**

#### *2.3.1 Criteria 1: effective vaccines*

The HPV Vaccines which are available in the Health care system are the Bivalent, Quadravalent and Nonovalent vaccines. They are prophylactic vaccines given to Girls between the age group 9–15 years, in doses as recommended by their Health care providers. The protective value of these vaccines are claimed to be more than 70%.

*Perspective Chapter: Cervical Cancer Elimination by 2030—The W.H.O Goal… DOI: http://dx.doi.org/10.5772/intechopen.104660*

## *2.3.2 Criteria 2: early diagnosis at precancer stages*

Various screening methods are available for the early diagnosis of Cervical Cancer, especially in the Precancer stages. The methods are VIA, Pap smear and HPV tests. These tests have high accuracy with acceptable levels of Sensitivity and Specificity. Further confirmation is done by Colposcopy and Cervical Biopsies. Hence, sure methods for diagnosis of pre cancer stages are available and the effective treatment of these lesions, prevent the stages of invasive Cervical Cancer. This is an important criterion for fulfilling the eligibility of Cervical cancer, for Elimination.

## *2.3.3 Criteria 3: effective treatment for cervical precancer*

The various treatment modalities available for the treatment of cervical precancer lesions:


All the above methods are very efficient for the treatment of Cervical precancers, resulting in Cure rates, up to 80–90%.

## **3. The WHO declares cervical cancer Elimination by 2030**

#### **3.1 Milestones**


### **3.2 The targets set by WHO, for cervical cancer elimination by 2030**

*3.2.1 HPV vaccination*

90% of girls to be fully vaccinated with the HPV vaccine by the age of 15 years [4].

## *3.2.2 Cervical cancer screening*

70% of women to be screened by VIA/Pap smear /HPV tests, by the age of 35 years, and again by the age of 45 years.

## *3.2.3 Precancer and cancer treatment*

90% of women with precancer lesions, to be treated. 90% of women with invasive cancer to be treated and offered Palliative care.

	- 1.Low levels of Awareness.
	- 2.Lack of Knowledge.
	- 3. Indifferent and negative Attitude.
	- 4.Poor Health seeking Behavior.

5.Very poor levels of Translation of Knowledge into Practice.


## **4. Discussion**

**Cervical Cancer Elimination by 2030 Neo Challenges and Next Gen Solutions "TIT for TAT" The Community Competency Model of Raj © "TIT"** Trained manpower—Indigenous resources—Translational research—**TIT "TAT"** Targets achievement—Action plan—Transformational research—**TAT**

The author recommends

**"TIT"as the Next Gen solutions "TAT"as the Neo challenges The Community Competency Model of Raj ©, for achieving Cervical Cancer Elimination by 2030.**

These recommendations are based on the "Proof of Concept ", Cervical Cancer Screening project of IARC/WHO, at Christian Fellowship Community Health Center, Ambilikai, Dindigul district, Tamil Nadu, India, during 2000–2007. The Author was the Principal Investigator of this project, which achieved a reduction in the

*Perspective Chapter: Cervical Cancer Elimination by 2030—The W.H.O Goal… DOI: http://dx.doi.org/10.5772/intechopen.104660*

Cervical Cancer Incidence by 25% and mortality due to Cervical Cancer by 35%, in a period of 5 years [5].

**Brief description of the model "TIT for TAT": NEXT GEN SOLUTIONS—"TIT" "TIT" T=T**rained manpower **I=I**ndigenous resources **T=T**ranslational research **NEO CHALLENGES—"TAT" "TAT" T=T**arget achievement **A=A**ction plan **T=T**ransformational research

#### **4.1 Next gen solutions = "TIT"**

#### *4.1.1 T = Trained manpower*

It is very important and prudent, to have the entire team, trained in their role, from authorized persons/organizations, and get certified, which are approved and accepted by the implementing authorities. Assessment exams are to be conducted at the start, concurrent and terminal levels to assure Internal Quality Control and Quality Assurance.

#### *4.1.1.1 Doctors*

To be trained in Colposcopy, Cryotherapy and LEEP/LLETZ, procedures. The author had his trainings with the fellowship from IARC/WHO, at RCSI—Dublin, RCOG—London, SCCPS—Singapore and served as a Hon. Consultant to the Cervical Cancer Screening Program of The Ohio State University Medical Center.

#### *4.1.1.2 Nurses/female health workers*

To be trained in Visual Inspection methods with Acetic acid—VIA, Lugol's Iodine—VILI Pap smear techniques, Endocervical curettage, Colposcopy guided Biopsy techniques, Cervical cells collection for HPV testing, technical assistance during treatment procedures and Counseling methods. Maintenance of clinical instruments, equipment, sterilization, autoclaving and laundry, which are very important tasks for the nurses.

#### *4.1.1.3 Lab technicians*

To be trained in Cervical Pathology and HPV testing procedures. The Medical Records staff needs to be trained in appropriate computer applications, Data management, data analysis, interpretation and publishing techniques.

#### *4.1.1.4 Health educators/counselor*

The participation of women for the Cervical Cancer Programs and compliance with the treatment and follow-up procedures, largely depends upon the level of Knowledge, Attitude and Practice. Even though, they may have adequate

knowledge regarding Cervical Cancer and its prevention, the proportion of women who will translate "Knowledge into Practice" is relatively small.

## *4.1.1.5 Knowledge—present/practice—absent*

The main barriers to achieving the above ambitious goal, are the lacunae and deficiencies in the conversion of knowledge into practice, by the women, who are otherwise well informed about the prevention of Cervical Cancer, as a result of massive inputs in the field of Health Education. Thus, the screening participation and compliance to precancer treatment remain low. This barrier in *translational knowledge* should be overcome efficiently. The author, by the virtue of his vast experiences, in planning and implementing one of the largest cervical cancer screening programs in India, has conceptualized "**The STAR P6 Health Education Model of Raj**© (6), for successful conversion of "Knowledge into Practice".

The STAR P6 Health Education Model of Raj© (**Figure 1**) [6].

## *4.1.1.6 The "P 6" concepts*

The STAR approach can be better explained under 6 aspects of the program:


The sole motive of the STAR approach is to encourage young women and girls for the HPV Vaccination and Screening of Cervical Cancer, applying the above mentioned 6 criteria, which involves a series of programmed and tailored steps in Health Education.

**Figure 1.** *The STAR P6 Health Education Model of Raj© [6].*

*Perspective Chapter: Cervical Cancer Elimination by 2030—The W.H.O Goal… DOI: http://dx.doi.org/10.5772/intechopen.104660*

### *4.1.2 I = Indigenous*

### *4.1.2.1 Indigenous resources*

The stability and sustainability of the Cervical Cancer Screening programs largely depend upon the **Availability and Affordability of Resources**. Instead of depending on distant and foreign resources which may be very costly and unaffordable, it is always prudent to develop locally available and affordable **Indigenous resources**, which would be functional and effective, even in limited and low resource settings. Some of the examples, that the Author has used in his WHO project are listed below:


## *4.1.3 T = Translational research*

The flow of knowledge, skills, technology, training, manpower, money and materials from a resource-rich organization, to resource poor and resource needed organization, is envisaged in Translational Research.

**Figure 2.** *Spectacles with lens attached—Indigenous Cervix scope.*

**Figure 3.** *Indigenous Colposcope and Cryotherapy Gun.*

The author mobilized resources from Ireland, UK, France, Singapore and USA, to get trained in Cervical Cancer Screening and treatment procedures. Experts from these countries, came to the project sites of the Author, in Tamil Nadu, India, to conduct workshops and Community Based Screening programs in the villages.

Thus the 3 concepts of "TIT"—Trained manpower—Indigenous resources— Translational research, were the Neo Gen solutions.

## **4.2 Neo challenges = "TAT"**

## *4.2.1 T = Targets achievement*

The WHO has set the Goal of Cervical Cancer Elimination by 2030. More than 190 countries are signatories to this declaration and have committed to the achievement of the Targets, set as follows:


## *4.2.2 A = Action plan*

	- 1.Every 30,000 population, should have a "Community Health Center—CHC". This should be accessible to all, and equipped with basic equipment, instruments, essential drugs for Primary Health Care.
	- 2.Each CHC should have 2 Female Community Health Nurses—CHN.

#### *Perspective Chapter: Cervical Cancer Elimination by 2030—The W.H.O Goal… DOI: http://dx.doi.org/10.5772/intechopen.104660*

**Figure 4.** *Cervical Health Evolution Cascade—CHEC.*

3.From every 5000 population, 2 Female Community Health Volunteers—CHV, should be identified and well trained in the practical aspects of Cervical Cancer screening and treatment (**Figure 4**).

*4.2.3 T = Transformational research*

*"Start from what you know, Build on what you have and Achieve on what you should" … .Raj—the Author*

The Health Care System tilts towards the Prevention of Diseases and Promotion of Health from the Curative and Remedial care (**Figure 5**).

## **5. Conclusion**

The main focus of this chapter is "Papilomaviridae Infections and Cervical Cancer—The Neo Challenges and Next Gen Solutions." The take home message is that HPV prevalence varies among region to region, communities to communities. The strains which infect the women are also multiple, varying in different countries and communities. The oncogenic strains of HPV are highly prevalent in Africa, Asia


#### **Figure 5.**

*The tilted balance for "Transformational Research".*

and American regions. Therefore, Cervical Cancer has a high incidence in these continents. The WHO has initiated a Goal—Elimination of Cervical Cancer by 2030.

The Neo challenges faced are listed under the phrase "TAT"

(Target—Action plan—Transformation).

T—Targets are the 90-70-90 of WHO. 90% of the girls in age group 9–15 to be fully immunised against HPV. 70% of the eligible women to undergo Screening for Cervical Cancer. 90% of the Precancers to be treated and palliative care to be offered for Cervical Cancer patients.

A—Action plan to create Primary Health Care infrastructure, in the communities through their full participation, contribution and ownership

T-Transformational Research, which shifts the paradigm of Health Services from Treatment based to Prevention focused, by use of Appropriate Technology for Health.

The Next Gen solutions are listed under the phrase "TIT". (Trained manpower—Indigenous resources—Translational research). *Perspective Chapter: Cervical Cancer Elimination by 2030—The W.H.O Goal… DOI: http://dx.doi.org/10.5772/intechopen.104660*

T—Trained manpower emphasizes on adequate training for the locally available and permanently employed Doctors, Nurses, Lab technicians, Health educators, Counselors and other paramedical staff of the programs, rather than relying on the specialists and temporary staff from external sources.

I—Indigenous resources, equipment, instruments and technology, are the accessible, affordable and available infrastructures for the efficient functioning of the programs, on a long-term basis.

T—Transformational research is based on shifting of the paradigm of Health care services from Treatment mode to Prevention mode.

Therefore, for the achievement of the WHO Goal of "Elimination of Cervical Cancer by 2030", the author, strongly recommends the TIT for TAT—The Community Competency Model of Raj© which effectively addresses the "Papilloma viridae infections and Cervical Cancer—The Neo Challenges and Next Gen solutions", both at regional and Global levels.

#### **Acknowledgements**

The author records his boundless love to Mary Ethalya Thiarathi, granddaughter, a baby angel of 2 years, for allowing him to write this chapter amidst so much pampering and playing. My sincere thanks to my family Ms. Celin Rani, Er. Rixon Raj, Dr. Rijula Raj, Er. Pavith Raj, for their excellent care and support, during my long hours of work, for editing this book and compiling this chapter.

The author is pleased to serve as Chief Editor, for his 7th book in this series, with the InTech Open Access Publishers. Their combination has the credentials of contributing to the "Advances in Academics and Revolution in Research", in the most pertinent, high priority fields of, "Cervical Cancer Prevention and HPV Vaccination", thus serving the Science and Society at Supreme levels.

We thank the Almighty, for keeping us safe and healthy, in these difficult times of war and pandemics, to serve for the community, in thoughts, words and deeds.

#### **Conflict of interest**

"The authors declare no conflict of interest."

#### **Author details**

Rajamanickam Rajkumar Meenakshi Medical College Hospital and Research Institute MAHER, Kanchipuram, Tamil Nadu, India

\*Address all correspondence to: rajcfchc@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## **References**

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[3] Available from: https://www.iarc. who.int/wp-content/uploads/2021/01/ CCAM\_Tile\_03\_zoom.jpg

[4] Available from: https://iarc.who. int/featured-news/iarc-marks-cervicalcancer-awareness-month-2022/

[5] Rengaswamy S, Okkuru EP, Rajamanickam R, Richard M, Rajaraman S, Sivanandam S, et al. Effect of visual screening on cervical cancer incidence and mortality in Tamil Nadu, India: A cluster-randomized trial. Lancet. 2007;**370**(9585):398-406

[6] Rajkumar R. HPV and Cervical Cancer Control Programs: Effective Translation of Knowledge in to Practice; IntechOpen; 2020. DOI: 10.5772/ intechopen.91313. Available from: https://www.intechopen.com/onlinefirst/hpv-and-cervical-cancer-controlprograms-effective-translation-ofknowledge-into-practice

## **Chapter 10**
