Genotype Distribution and Seroepidemiology of Human Papillomavirus (HPV) in Female Population of Bangladesh

Abstract

Cervical cancer is one of the most prevalent cancer that develop in the cervix of the women worldwide. Annually 266,000 deaths are reported from 528,000 new cases of cervical cancer, which approximately account for 8% mortality of all female cancer patients. The most severe risk factor for cervical cancer till now is considered as an infection with specific human papillomavirus (HPV) types. The socioeconomic conditions of Bangladesh are constantly being threatened by an increasing concern regarding to the high mortality rate from this disease. Although several researches related to the epidemiology, HPV vaccination, and to some extent treatment protocols have been carried out in our country, any research regarding the prevalence and genotyping of HPV, on serology to detect potential biomarkers and on mutation profiling of several specific genes in cervical cancer in Bangladesh is yet to be done. As we know that different types of HPVs are involved in infection, so the genotyping might reveal the high risk factors in both cervical cancer patient and apparently healthy women. It has been found that in case of cervical cancer 113 patients out of 115 (98.26%) are infected with HPV whereas 121 out of 410 (29.5%) apparently healthy women are infected with HPV. However, in this study we have presented that the age of women (Significant, p value <0.05), early exposure to sexual intercourse (Significant as p value <0.05), early pregnancy, multiple sexual partner, socioeconomic status (significant as p value <0.05), use of contraceptives, husband’s occupation (Significant as p value <0.5) and the education level of the patient (Significant as p value < 0.05) etc. are among the several risk factors. Also we attempted to find out the responsible genotypes of HPV for the infection which later on might cause cervical cancer. Among the different types, this might be said that most prevalent genotype is HPV type 16 (53.7%) and HPV type 18 (19.06%) and their combinations (26.27%). Furthermore it has been observed that, apart from the HPV type 16 and type 18, also some other HPV types like type 6, type 62, type 69, type 31, type 33, type 90, and type 70 might also be responsible. In case of sera samples this study justifies some of the goals to find out the potential biomarkers considering HMGB1 (High mobility group box 1), CEA (Carcinoembryonic antigen). Serpin B3/SCCA Squamous cell carcinoma antigen) and Cytokeratin fragment 21-1 proteins, where it has been found that CEA was the prevalent protein to be shown in most of the patient’s sera. Here, it also has been tried to detect possible correlations of antibody against HPV type 6, type 11, type 16 and type 18 in case of disease progression. Finally, among the high number of genes involved in different signal transduction and cell growth regulation pathways, five different genomic regions within the top three most frequently mutated genes in COSMIC database with a key role in the development of cervical cancers were selected to study mutation frequency in our patients. These genes are EGFR (Epidermal Growth Factor Receptor), KRAS (Kirsten rat sarcoma), and PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha). In total, 39 mutations were found in 28 patient samples. Eleven different mutations (23.91%) were found in amplified EGFR gene fragments, among which 1 was common in seven patient samples. On the other hand, twenty-four different mutations (52.17%) were found in PIK3CA gene fragment amplicons, among which 2 were found in more than 1 patient. Four mutations (8.7%) were found in KRAS gene fragment amplified products. It has also been found that except for KRAS, the frequency of observed mutations in our patients is higher than those reported earlier in other parts of the world. Our study finally summarizes that in case of Bangladesh the most considerable prevalent type of HPV might be HPV type 16 and type 18 and also to some extent their combinations. If serological study could be done further comparing with the control patient than established diagnostic tool could be generated. And also after the mutation profile study. The study can be used as a basis to build a mutation database for cervical cancer in Bangladesh. With the possibility of further exploration can be oriented towards establishing future diagnostics, personalized medicine decisions, and other pharmaceutical applications for specific cancer subtypes.