HPV Genotypes and Epidemiology in Women With Cervical Cancer in Senegal

In sub-Saharan Africa, cervical cancer is increasing steadily, with more than 75,000 new cases and nearly 50,000 deaths a year In Senegal, pathologies such as cervical cancer are at the top of the causes of death and Human papillomavirus (HPV) is the aetilogical agent The aim of the study is to analyze the distribution of HPV among Senegalese women with cervical cancer. Main objectives of this study are to identify the HPV types associated or “co-associated” with cervical oncogenesis in Senegal. The correlations with risk factors of cervix carcinogenesis, with risk factors, were analyze too. Cervical biopsies were performed on women hospitalized at Aristide Hospital Le Dantec-Julio Curie Institute. Three methods has been used to detect HPV genotypes - SANGERsequencing genotyping (Applied BioSystems), PCR real-time approach technique (HPV 16 & 18 RealTime PCR kit) (www.bioneer.co.kr) and the genotyping approach from Chippron (HPV kit 3.5 LCDArray) (info@chipron.com).


Abstract Background
In sub-Saharan Africa, cervical cancer is increasing steadily, with more than 75,000 new cases and nearly 50,000 deaths a year (Mboumba et al., 2017). In Senegal, pathologies such as cervical cancer are at the top of the causes of death and Human papillomavirus (HPV) is the aetilogical agent (Steenbergen et al., 2005).

Methods
The aim of the study is to analyze the distribution of HPV among Senegalese women with cervical cancer. Main objectives of this study are to identify the HPV types associated or "co-associated" with cervical oncogenesis in Senegal. The correlations with risk factors of cervix carcinogenesis, with risk factors, were analyze too. Cervical biopsies were performed on women hospitalized at Aristide Hospital Le Dantec-Julio Curie Institute.

Results
It this study, patients had multiple infections (co-infections) at all, and the majority of coinfections was High-risk types (HR-HPV types). The most common type of HPV in our study were 16 (34.37%), 18 (23.29%), 45 (10.75%), 33 (9.94%), 59 (9.09%), (3.97%) and 31 (3.69%). Among co-infections detected in different regions of Senegal among women with cervical cancer, we found that HPV types 16 and 18 had the highest prevalence. In the Dakar region, which had the highest number of cases, a prevalence of 17.89% of HR-HPV co-infections was noted.

Conclusion
Polygamy represents a cofactor in the occurrence of cervical cancer in Senegalese women.
No association between HPV-High Risk co-infections and cancer stages.

Background
Cervical cancer is the fourth commonest cancer affecting female population in the world, and the seventh most common cancer in the general population worldwide (Bray et al, 2018). The disease is also the fourth leading cause of cancer death among women with 311,000 associated deaths in 2018. The highest regional incidence and mortality rates are seen in Africa, especially in Eastern (Malawi, with the highest mortality rate ; and Zimbabwe) and Western Africa (Guinea, Burkina Faso, and Mali). Globally, it was previously admitted that low-and middle-income countries account for almost 90% of the burden of cervical cancer (WHO, 2014) due to insufficient awareness, lack of effective screening programs, and late clinical presentation. In addition, reports of trends in cervical cancer mortality in these countries have been limited by poor data quality and We noted that co-infections with several HR-HPVs were predominant in polygamous patients (p value of 0.028) compared to patients with monogamous status (OR of 0.30).
For gestationality criterion, coinfections with multiple genotypes (up to 8 genotypes) were more frequent in patients who had 6 pregnancies or more (OR = 1.60). We also noted that co-infections with multiple genotypes were signicantly associated to patients older than 45 years (OR> 1). The association analysis between HRHPV coinfections and age showed that HR-HPV co-infections were more prevalent among "young" patients (<45 years old) with 35 cases and those aged between 45 and 55 years (41 cases). In both groups, coinfection with more than 2 HR-HPV genotypes dominated (79 cases vs 41 with 2 or less).

Discussion
Cervical cancer (CC) is a scourge that imposes a therapeutic emergency. This cancer is increasing steadily in sub-Saharan Africa, with more than 75,000 new cases and nearly worldwide, and will kill more than 443,000 people worldwide by 2030, nearly 90% of them in sub-Saharan Africa. This high incidence may be justified by the lack of adequate structure for diagnosis, screening and treatment (Castellsague et al., 2007). In Senegal, CC is the first most common cancer of women (Refs….), and here we reported a pilot study exclusively dedicated to the distribution of HPV genotypes among Senegalese women with cervical cancerous lesions.
As expected, all cervical specimens collected in women with histologically confirmed ICC were HPVpositive with at least one genotype detected. The most commonly detected HPV types in women with single or multiple HPV infections were HPV16 (54.16%), HPV18 (33.33%), HPV45 (26.66%), HPV33 (20.83%), HPV59 (18.33%), HPV35 (11.66%) and HPV31 (10%). The high prevalence of HPV16 and HPV18 reported in our study was expected, since these types are the two most common HPV types across the world (de Sanjose et  However the mechanism how multiple HPV infections affects patients survival is not fully understood. We also noted that co-infections with more than 2 HR-HPV types were especially prevalent in patients between 45 to 55 years age, probably due to viral persistence or reactivation of latent HPV (Simon and Poppe 2008; Dufit et al., 1991).
With regard to marital status, multiple HR-HPV co-infections were significantly more prevalent among polygamist. We also noted that women with more than six pregnancies were prone to multiple coinfections. Both results are in line with previous results which clearly indicated that multiple pregnancies and the high number of sexual partners increase the risk of HPV infection and persistence (IARC, 2016).
Other cofactors, such as environment and smoking were also known to modulate the Regarding the vaccination perpectives, the relatively high prevalence of the non vaccine types HPV59 (18.33%) and HPV35 (11.66%) could be a public health issue in Senegal, but once again additional studies are needed to confirm these findings.
However some limitations can be pointed out of this study. Firstly, the modest sample size included in this study. Indeed, infortenately only few cases were sampled and tested, and the HPV genotypes prevalence reported here should be considered as trends which need confirmation through additional more exhaustive studies. Secondly, the high prevalence of multiple infections, sometimes with more than 3 genotypes, complicates the establishment of the carcinogenic value of some HPV types or group of HPV types. Genotypes viral load determination by quantitative methods would probably help to have an idea about the more carcinogenic types or combinations 'types' associated with (ICC) in Senegal.

Conclusion
In conclusion, the overall frequency of HPV types detected in cervical cancerous lesions was high for HPV16 and HPV18 in Senegal. Multiple infections were also very common.
Globally, our findings can be beneficial to health policy decision-makers and shows that current HPV vaccines, especially the current 9-valent one, could have great impact to