Human Papilloma Virus: Where are we?‘Human papilloma virus (HPV) is the most common sexually transmitted infection worldwide, with approximately 80% of women having acquired an infection by the age of 50’(Braaten, K.P and Laufer, M.R. 2008). ‘Though most HPV infections clear off, but persistent HPV infection is strongly associated with risk of cervical cancer and genital warts’ (Braaten, K.P., and Laufer, M.R. 2008).‘HPV is a double- stranded DNA virus which infects the squamous epithelial cells such as skin, oral, vaginal, anal and nasal epithelium’ (Hathaway, J.K. 2012). According to Eloise Chapman-Davis et al. 2016, ‘infection with human papilloma Virus (HPV) is the major cause of pre-invasive and invasive lesions of the uro-genital tract, which results in morbidity and mortality (Chapman-Davis, E. et. al.,2016) and is responsible for most cancer cases which is a leading cause of death in women worldwide’ (Chapman-Davis, E et. al. 2012). However, Godoy-Vitorino, F et. al. 2018 states that: ‘ Human papilloma Virus (HPV) infection and cancer rates are higher in Puerto Rican women (Hispanic) as well as women of Black race( Godoy-Vitorino, F. et al. 2018), when compared with Caucasian women of their age and this could be due to a higher prevalence of circulating HPV infections as well as lower screening rates in these group of women, and socio-economic factors together with few or less access to treatments such as, screening for cervical cancer’’( Godoy-Vitorino, F. et al. 2018).However, Monie, A., Hung, C.F., Roden, R., and Wu, T.C. (2008), also defined HPVs as ‘’non-enveloped icosahedral viruses, with a circular, double-stranded DNA genome’’. ‘’ This genome encodes two classes, which are; early and late genes’’( Monie, A., Hung, C.F, Roden, R., and Wu, T.C. 2008). ‘’ This early gene products, has been found to regulate viral DNA replication (E1,E2), viral RNA transcription ( E2), cytoskeleton reorganization (E4),( Monie, A., Hung, C.F., Roden, R. and Wu,T.C.2008) and cell transformation (E5, E6, E7), while late proteins (L1,L2), are structural components of the viral Capsid’’( Monie, A., Hung, C.F., Roden, R and Wu, T.C. 2008). ‘’ The expression of viral proteins is however, tightly regulated and also reported to be associated with the differentiation of infected epithelial cells’’( Monie, A., Hung, C.F., Roden, R and Wu, T.C. 2008).In addition,’’ E2 is also found to be the master regulator, which regulates the expression of the other viral genes (Monie, A., Hung, C.F., Roden, R. and Wu, T.C. 2008) and is also involved in the repression of E6 and E7’’(Monie, A., Hung, C.F. Roden, R and Wu, T.C. 2008). ‘’ The viral oncogenes E6 and E7 are thus responsible for thus responsible for transformation, which helps the HPV genome to integrate into the host ( Monie, A.,Hung, C.F., Roden, R. and Wu, T.C. 2008) chromosomal DNA’’. ‘’The fact that E2 is a transcriptional repressor of E6 and E7, the loss of E2 gene, therefore, leads to the upregulation of E6 and E7 gene (Monie, A., Hung, C.F. Roden, R and Wu, T.C. 2008), and thereby elevating the expression of E6 and E7 gene protein, which results in the disruption of cell cycle regulation and thus, leading to genomic instability ( Monie, A., Hung, C.F., Roden, R and Wu, T.C. 2008).‘’ This finally contributes to the progression of HPV-associated cervical cancer’’( Monie, A., Hung, C.F., Roden, R. and Wu, T.C. 2008).‘Some Research conducted between the years 1990-2000 found a ‘ temporal association between exposure to high-risk (HR) Human papilloma Virus (HPV) and the further development of cervical intraepithelial neoplasia (CIN) and cervical cancer’( Gravitt, P.E and Winer, R.L. 2017), as well as the temporal pathway from HPV infection to invasive cervical cancer (ICC) (Gravitt, P.E. and Winer, R.L. 2017).‘’Apart from HPV, the risk factors related with the onset of cervical cancer (Asiaf, A. et al. 2014) are early-age sexual activities,( Between ages 15-25years) such as, long-term use of oral contraceptives and other hormonal influences, as well as high number of sexual partners’’ (Asiaf, A. et al. 2014). ‘The tumor-suppressor proteins p53 and PRb are degraded and destabilized through ubiquitination by viral oncogens E6 and E7’’(Asiaf,et al. 2014).‘The high-risk HPV (oncogenic) types include; HPV16,18,31,33,35,39,45,51,52,58and 59 (Godoy-Vitorino et al. 2018), that are associated with cervical, vulva, vaginal and anal cancer progression, while the low rise types (Godoy-Vitorino, F, et al. 2018) such as 6,11, 40,42 ,43,44 and 54 are found to be associated with genital warts and low grade anogenital tract lesions’’(Godoy-Vitorino, F. et al. 2018). Furthermore, ‘These types of HPVs are called 1A Carcinogens (Arbyn, M. et al. 2014 ) and this is because they belong to the family of alpha-Papillomaviridae, especially the alpha-5 (HPV 51), alpha-6 (HPV 56), and alpha-7(HPV 18, HPV39, HPV 45, HPV 59) and alpha-9’ (Arbyn, M. et al. 2014).In addition, ‘the increased prevalence of HPV in HIV-infected women (Theiler, R.N. et al. 2010) is most probably due to higher rates of incidence of HPV infection because of sexual risk factors and the decrease in their ability to clear (Theiler, R.N. et al. 2010) established infections in the face of HIV-associated immunosuppression’’(Theiler, R.N. et al. 2010). However, ‘’women with a history of cervical HPV infection (Theiler, R.N. et al. 2010) may thus be at risk of reactivation of latent viral infection when they are not sexually active and this is specifically higher in women with HIV infection’’(Theiler, R.N. 2010).According to Muller et al. (2010), however, ‘The outcome of HPV infection depends on the specific types of HPV present which can range from a- symptomatic infection to severe squamous malignancies [ Muller E. E. et al,2016), and low-risk HPV types such as types 6 and 11, which are associated with anogenital warts and mild dysplasia, while high-risk types such as HPV 16 and 18 are associated with high-grade dysplasia and cancers of the cervix, vulva, vagina, urethra, penis, anus and oropharynx’’( Muller, et al.2016).Figure 1 above shows ‘The Natural history of HPV from infection to cervical cancer stage ( Gravitt, P.E and Winer, R.L. 2017). HPV infections are acquired via sexual exposures, with newly sexually active adolescent and young adult women at highest risk of acquisition (Gravitt,P.E and Winer, R.L 2017).Figure 2 Diagram above shows ‘more complete elucidation of the age-specific probabilities of the alternative transitions, which is becoming more relevant with the expanded use of HPV testing in Cervical cancer screening’’( Gravitt, P.E and Winer, R.L. 2017).Similarly, Human Papilloma virus, which is an independent risk factor for the acquisition of Human Immunodeficiency virus (HIV), (Muller, E.E. et al, 2016), is also associated with an increased risk of acquiring new HPV infections, as well as a decrease in the rate of HPV clearance, has been reported as one of South Africas highest HIV prevalence rates ( Muller, et al. 2016) globally and is estimated with a prevalence of 12.2% in general population in 2012’’( Muller, E.E et al. 2016). ‘’Hiv is reported to be highly prevalent in men-who-have-sex-with-men (MSM) and is estimated with a prevalence rate of 22.3%, 26.8%, and 48.2% in Cape Town, Johannesburgh, and Durban’’( Muller, et. al 2016).Moreover, a research carried out by Senkomago, V. et al. (2015), found that ‘’circumcision and low-HPV viral loads in men are most likely associated with a reduced risk of HPV transmission to their female partners, while the association between male circumcision and HPV viral loads still remain unclear’’(Senkomago, V.et al. 2015). In addition, ‘’ persistent infections with high-risk Human Papilloma virus (HPV) type 16 (HPV-16) and HPV type 18 (HPV-18) has been reported to cause approximately 70% of cervical cancer cases in women (Senkomago, V. et al. 2015), while women with higher HPV-16 or HPV -18 viral loads are more likely to have persistent infections which will progress to high grade cervical Intraepithelial neoplasia(CIN), than those with lower viral loads (Senkomago, V et.al. 2015). Also, ‘’men with higher HPV-16 or HPV-18 viral loads have a higher prevalence of flat penile lesions and greater HPV type concordance with their female partners than those with lower viral loads (Senkomago, V. et al. 2015) and therefore, a higher viral load in men is suggested to be associated with an increased risk of HPV transmission to their female partners’’( Senkomago, V. et al. 2015).Human Papilloma Virus Vaccines‘’The vaccines currently available and designed to prevent HPV-associated cancer to some HR-HPV genotypes (Muller, E.E. et al. 2016), are: bivalent Cervarix HPV vaccine by Glaxo-SmithKline, which targets HPV types 16 and 18 (Muller, et al.. 2016), the quadrivalent Gardasil HPV Vaccine by MSD, which targets types 6,11,16 and 18 (Muller, E. E. et al. 2016) ad the 9-valent Gardasil.  9 HPV vaccine by MSD, which targets HPV types 6,11,16,18,31,33,45,52 and 58’’ (Muller, E.E. et al.2016). ‘’Cervarix , however, ‘ produced using insect cells infected with recombinant baculovirus (Monie, A., Hung, C.F., Roden, R and Wu, T-C. 2008), and formulated in the proprietary adjuvant ASO4’’ ( Monie, A., Hung, C.F., Roden,R and Wu, T-C.2008) and this consists of alum combined with a TLR4 ligand, MPL’’(3-0-desacyl-4-monophosphoryl lipid A.)’’( Monie, A., Hung, C.F., Roden, R and Wu, T-C.2008). ‘’ Cervarix vaccine requires three intra-muscular doses and its main effect is to protect from HPV-related squamous intraepithelial neoplasia lesions (SIL)’’ (Monie, A., Hung, C.F., Roden, R. and Wu, T-C. 2008). ‘’ The HPV types used to derive the vaccine (Monie, A., Hung, C.F., Roden, R and Wu,T-C. 2008). ‘’ Cervarix vaccine has been reported to be well tolerated from trials, highly immunogenic and effectively generates 90% high level titres of neutralising antibody to the HPV types 16 and 18 (Monie, A. Hung, C.F., Roden, R and Wu, T.C. 2008).However, ‘’Gardasil also requires three doses intra-muscularly, produced from yeast (Monie, A., Hung, C.F., Roden, R and Wu, T-C. 2008), both Cervarix and Gardasil are quite expensive in developed countries, with each vaccine costing $100 and $120 U.S. Dollars respectively’’( Monie, A, Hung, C.F, Roden, R and Wu,T-C. 2008), which thus makes it difficult for patients in developing countries to acuire’’( Monie, A., Hung,C.F., Roden, R and Wu, T-C. 2008). Recent data from Jit. M. et al. 2011, shows that, ‘’the quadrivalent vaccination protects against intraepithelial neoplasias of the vulva, vagina and anus, which could progress into invasive Carcinoma (Jit. M. et all. 2011), while penile and oropharyngeal cancers have been linked with HPV 16 or 18’’(Jit, M. et al 2011).ReferencesBraaten, K.P and Laufer, M.R. Human Papilloma virus (HPV), HPV-Related Disease, and the HPV vaccine. Rev Obstet Gynecol 2008 Winter; 1(1):2-10.Hathaway, J.K. HPV: Diagnosis, Prevention and Treatment. Clinical Obstetrics and Gynecology; vol 55 (3), Sept 2012, pp 671-680. Doi:10.1097/GRF.Ob013e31825caa36.Chapman-Dans, E., Dockery, L.E., Griffith, K., Stroup, C. Update on Human Papilloma virus vaccination: Where are we now? World J Obstet Gynecol. Feb 10, 2016; 5(1):5-15. Available online: Doi: 10.5317/wjog. vs. i1.5. (http://dx.doi.org/10.5317/wjog.vs.i1.5).Godoy-Vitorino, F. et al. Cervicovaginal fungi and Bacteria Associated with Cervial Intraepithelial Neoplasia and High-Risk Human Papilloma virus Infections in a Hispanic Population. Front Microbiol.2018;9:2533. Available online: Doi:10.3389/fmicb.2108.02533).Monie, A., Hung, C.F., Roden, R. and Wu, T-C. Cervarix: a vaccine for the prevention of HPV 16, 18-associated cervical cancer. Biologics 2008 Mar; 2(1): 107-113.Gravitt, P. and Winer, R.L. ‘Natural History of HPV infection across the lifespan’; ‘’Role of viral latency’’. Viruses. 2017 Oct; 9(10): 267.  Available online: Doi/10.3390/v9100267).Asiaf et al. Review of the current knowledge on the epidemiology, pathogenesis and prevention of Human Papilloma virus infection. Eur. J Cancer prev. 2014 May; 23(3): 206-24. Doi: 10.1097/CEJ. 0b0133e328364f273.Theiler, R.N. et al. High-Risk Human Papilloma virus Reactivation in Human Papillomavirus immunodeficiency virus- infected women: Risk factors for Cervical viral shedding; Obstet Gynecol. 2010 Jun; 115(6): 1150-8. Available online: Doi 10.1097/AoG.0b013e3181e00927.Arbyn, M., Tommasino, M., Depuydt, C., and Dillner. J. Are 20 Papilloma virus types causing cervical cancer? The J Pathol. 2014 Dec; 234(4): 431-5. Doi: 10.1002/path.4424. Muller, E.E et.al. The Prevalence of Human Papilloma virus Infections and Associated Risk factors in Men-who-have-sex-with-men in Cape Town, South Africa: BMC Infect Dis. 2016; 16(1):440. Available online: Doi:/10.1186/s12879-016-1706-91/. Senkomago, V. et al. Acquisition and persistence of Human Papilloma virus 16 (HPV-16) and HPV -18 Among men with High-HPV viral load Infections in a circumcision trial in Kisumu, Kenya. J Infect Dis. 2015 Mar 1; 211(5):811-820. Doi: 10.1093/Infdis/jiu 535. Fu, T.C et al. Re-detection versus New acquisition of High-Risk Human Papilloma virus in Mid-adult women. Int J Cancer.2016 Nov 15; 139(10):2201- 2212. Doi:10.1002/ijc.30283. Epub 2016 Aug 4. Jet, M.et al: Comparing bivalent and quadrivalent Human Papilloma virus vaccines: economic evaluation based on transmission model. BMJ 2011; 343. Doi: https: //doi.org/10.1136/bmj.d5775.Get Help With Your EssayIf you need assistance with writing your essay, our professional essay writing service is here to help!Find out more