Epidemiology of Human Papillomavirus - Research Paper Example

? Epidemiology Epidemiology is the study of occurrence, spread and the quantification of the mechanism that underlies the disease to the healthy population. The epidemiological studies help the practitioners to find out the root cause of the disease and develop the treatment methods accordingly. Epidemiology is deals with the determinants and distribution of the disease frequency among the population. Epidemiological studies require knowledge in the fields of biostatistics, social and behavioral sciences, clinical medicine, microbiology, toxicology, genetics and pathology. (Friis and Sellers, 2009). Epidemiological activity is used since many decades. The statistical tools are the most powerful device used for identifying the risk factors and the relationship between various factors such as environmental factors, drugs, genetics, hormones, occupation, nutrition and viruses, bacteria. It was the epidemiological studies that revealed the relationship between Human Papilloma Virus (HPV) and cervical cancer. (Friis and Sellers, 2009). The US centre for Disease Control and Prevention [CDC] estimates that most of the new cases of HPV are teens and young adults. They have estimated that 6 million new cases are recorded every year in US. In 2007, the CDC has announced that one among the four teenage girls ages 13 to 19 are having HPV. Among the teens, 40 percent of the children who had sex were found to have Human papilloma virus. (Lyon and Antoniades, 2009). Similarly CDC has also found that 20 Americans are infected with the HPV and many of them are not aware of it. Uses of Epidemiology 1. To study the history of the disease and the changes in the disease states. It also helps to study the history of the healthy populations in the locality. 2. To measure the true dimension of the disease and the healthy individuals. The prevalence of the disease based on the risk factors, the distribution of disability and mortality can be understood using epidemiological studies. 3. The services provided by the health centers can be monitored very well using these studies. (Friis and Sellers, 2009). 4. The identification of the risk factors associated with the disease are identified using the epidemiological studies. 5. The association of the clinical phenomena and the risk factors are well understood using the epidemiological studies. (Friis and Sellers, 2009). 6. To identify the root of the chronic diseases and provide the complete history of the diseases to help the practitioners and people eradicate the disease from the epidemic regions. 7. To confirm the risk factors and causes of the disease using the knowledge obtained through studies for the risky and multiple causative disease. (Friis and Sellers, 2009). Human Papilloma virus: Papilloma viruses are DNA viruses that infect epithelia causing a variety of lesions, warts and carcinoma. Human Papilloma viruses (HPV) are ubiquitous in nature causing cervical and other anogenital cancers. HPV infections are most common in the young and sexually active people within the age limit of 20 – 24. Human papilloma viruses form two groups; Genital and cutaneous HPVs. Most of the papilloma viruses are host specific. Human papilloma virus has an icosahedral symmetry with 72 capsomers arranged in the pentameric structure. It has a circular double stranded DNA of 8 kb long. It has three types of genes: early genes, late genes and control genes. HPV first infects the basal epithelium and inserts itself into the cell. It then dissociates and produces low copy number episomes. The HPV gets loosely linked to the keratocyte differentiation and divides as the keratinocyte undergoes differentiation. The major oncogenic proteins involved in the HPV carcinogenesis are E6 and E7 which interfere in the cell cycle control mechanisms. E6 on binding with the cellular protein AP, degrades the p53 through ubiquitin- directed proteolysis. P53 is essential for DNA repair, when this molecule is degraded; it affects the ell cycle control. The result is genetic instability and accumulation of the mutants in the skin. Figure 1: Genome organization of Human Papilloma virus- 16. (Leitner, 2002) More than 40 types of HPV are found to spread from person to person through anal vaginal and oral sex. They are the most common sexually contacted disease in the world. High risk Human papilloma virus causes about 5 % of the cervical cancer world wide. . (Burd, 2003).They mainly cause lesions and cytological abnormalities in the skin. Most of the cervical cancer is caused by HPV 16 and 18 types. (Burd, 2003). Cervical caner is the third most common disease among the American women. It constitutes about 25% of the cancers in women. There is high association between HPV and cervical squamous cell carcinoma than the association between smoking and lung cancer. (Burd, 2003). Risk factors of cervical cancer: 1. Sexual activity at the early ages. 2. High risk – sexual partner. 3. History of sexually transmitted disease. 4. Immunosuppression. 5. Multiparity. 6. Cigarette smoking. ( Rosenblatt and Guidi, 2009). Epidemiology of HPV infection The transmission of HPV mainly occurs by skin to skin contact. The epidemiological studies clearly indicate that cervical cancer and HPV infection are strongly related. The sexual activity at early ages plays an important role for increases risk for cervical cancer. Most of the cervical caner occurs at the region between columnar epithelium of the endocervix and the squamous epithelium of the ectocervix. This region receives continuous metaplastic changes. This metaplastic activity is higher at the puberty, reduces a little during pregnancy and declines after menopause. (Burd, 2003). Thus HPV infection is most common in sexually active young women between 18 – 30 years of age. Cervical cancer is found to be influenced by oral contraceptives, smoking and parity. Similarly the infection with cytomegalovirus, human herpes virus 6, and herpes virus 7 increases the infection. Figure 2: Age related rates for HPV and cervical cancer. (WHO, 2008). The oncogenicity of the HPV variants varies with the geographical location. Asian – American variants have enhanced oncogenetic activity compared to European isolates. European HPV variants have point mutations in the LR binding site. (Burd, 2009). International prevalence surveys conducted in 22 countries for invasive cervical cancer without control studies and in 13 countries with control studies have concluded that invasive cervical cancer were HPV DNA positive. HPV 16 variant are of African origin and HPV-18 is of Alaska and America origin. Pathogenesis HPV invades the superficial layers of the epidermis and infects the cells present in the stratum spinosum. After the invasion it stimulates the cell division. This results in the cell proliferation and formation of Wart like projections in the vagina, vulva, penis, rectum, anus, and perineum. The infections are also seen in the oral mucosa. (Langford and Thompson,2005 ). Genital warts do not cause symptoms. They are found to occur in the regions of friction such as cervix, vagina, urethra, vulva, scortum and penile shaft. They appear as cauliflower like condylomata acuminatum with thick horny layers of pigmentation. Biopsy of warts can determine the prevalence of cervical cancer. Human papilloma virus 6 and 11 causes most of the genital warts. (Weaver, 2006). Clinical manifestations: Projections which appear in genital, perianal and oral mucosa as soft, moist fleshy pink to brown clusters are the outcomes of HPV infection. Table 1: Diseases and Associated HPV Subtypes (Gearhart, Randall and Burkley, 2011). Anogenital Disease HPV Type Condylomata acuminata 6, 11, 30, 42, 43, 44, 45, 51, 52, 54 Bowenoid papulosis 16, 18, 34, 39, 42, 45 Bowen disease 16, 18, 31, 34 Giant condylomata (Buschke-Lowenstein tumors) 6, 11 Unspecified intraepithelial neoplasia 30, 34, 39, 40, 53, 57, 59, 61, 62, 64, 66, 67, 68, 69 Low-grade intraepithelial neoplasia 6, 11, 43 Intermediate intraepithelial neoplasia 31, 33, 35, 42, 44, 45, 51, 52 High-grade intraepithelial neoplasia 16, 18, 56, 58 Carcinoma of vulva 6, 11, 16, 18 Carcinoma of vagina 16 Carcinoma of cervix 16, 18, 31 Carcinoma of anus 16, 31, 32, 33 Carcinoma in situ of penis (erythroplasia of Queyrat) 16 Figure 3: Most prevalent HPV types that cause cervical cancer in humans. (Weaver, 2006). Figure 4: Piechart giving the association of HPV infection in cancer: (Gearhart, Randall and Burkley, 2011). Table 2: Prevalence of HPV infection among women in United States: (Steben and Duarte- Franco , 2007). Age ( years) Prevalence (%) 14 - 19 24.5 20 - 24 44.8 25 - 29 27.4 30 - 39 27.5 40 - 49 25.2 50 - 59 19.6 Figure 5: Increase in the HPV infection in young women based on the number of sex partners. . (Weaver, 2006). Screening for HPV Cytological testing and HPV DNA typing are the two standard methods for the cervical neoplasia. In the cytological testing pap smears are collected and pap test is performed. The Pap smears should contain the cells from the ectocervix, transformation zone and endocervical canal. Thin Prep and Sure Path are the two tests now approved by the FDA. This is the primary method for the detection of the high-risk HPV. Apart from conventional cytology, monolayer cytology is also practiced. (Gearhart, Randall and Burkley, 2011). HPV DNA typing is the preferred approach to test HPV in women. 2 common methods of HPV testing include hybrid capture II (HC II) and polymerase chain reaction immunosorbent assay. These two methods are very sensitive and can be used for the detection and post – treatment effect of HPV especially for cervical intraepithelial neoplasia. (Evans and Kaslow, 1997). However the confirmation for the HPV infection is through tissue Biopsy only. The DNA typing is performed using Southern Blot, filter insitu hybridization, true insitu hybridization, dot blot and hybrid capture techniques..(Nasta and Pastides, 2001). Prevention Vaccination is the best method for prevention of cervical cancer. There are two vaccines currently in usage. They are Gardasil (Merck) and Cervarix (Glaxosmithkline). These vaccines should be given in three shots within six months. Of these two vaccines Gardasil can prevent genital warts, anal, vulvar and vaginal cancers. (“Sexually Transmitted Diseases”, 2011). HPV vaccines can be administered to young women between 9 – 26 years. These vaccines are approved by Food and Drug Administration (FDA) as safe and effective drugs. These vaccines are not recommended for women above 26 years. Similarly quadrivalent vaccine is safe and effective for boys and men between 9 – 26 years. This vaccination prevents anal and genital warts. After vaccination the young men and women are recommended to undergo follow up and routine checkup. Apart from vaccination, the use of condoms will reduce the chance of getting HPV. Condoms will also reduce the risk of developing other HPV related infections. Moreover limiting the number of sex partners will overcome all the troubles of HPV and cervical cancer. Having one sex partner is the best method to reduce the infection and other risks of HPV but that is not the only way to reduce HPV. (“Sexually Transmitted Diseases”, 2011). Treatment Immunoresponse modifiers and cytotoxic agents are used for treating HPV infections. Imiquimod, interferon alfa are primarily used in the treatment of external anogenital warts. Some antiproliferative drugs such as podofilox, podophyllin and 5-fluorouracil and keratolytic agents such as salicyclic acid and Trichloroacetic acid are used in the treatment of HPV infections. (Gearhart, Randall and Burkley, 2011). Imiquimod: This is a very powerful cytokine inducer and used for the treatment of the external anogenital warts. Interferon alfa: This is a potent immunomodulatory agent with antiviral effects. This is a physician applied medicine for treating external anogenital warts. Podofilox: This is an antimitotic drug used at a concentration of 0.5 g per day for the treatment of external warts only. The other drugs are also used for the treatment of the warts and they are effective in reducing the warts and the lesions. (Gearhart, Randall and Burkley, 2011). Conclusion: Human papilloma virus is DNA virus linked with the cancers of the cervix, anal, vagina and aerodigestive tract. It is most prevalent in young men and women. Even the teens are affected much by this disease. Prevention is better than cure. Hence the use of vaccination against cervical cancer is preferred. The vaccinations are effective against young men and women of age between 9 -26. The vaccines should be administered as triplet dose for women and quadrivalent dose for men. References Burd, EM. (2003). Human Papilloma virus and cervical cancer. Clinical Microbiology reviews, 16 (1): 1 – 17. Evans, A. S & Kaslow, R. A. (1997). Viral infections of humans: epidemiology and control, Volume 813, Springer. Friis, R.H & Sellers, T. A. (2009). Epidemiology for Public Health Practice. Jones and Bartlett learning. Gearhart, P. A., Randall, T. C and Burkley, R. M. (2011). Human Papilloma virus. Retrieved from: http://emedicine.medscape.com/article/219110- overview#a0199. Langford, R & Thompson, J. D. (2005). Mosby’s Handbook of diseases. Elsevier Health Sciences. Leitner, T. (2002). The molecular epidemiology of human viruses, Springer. Lyon, M. E and Antoniades, C. B. (2009). My teen has had Sex, Now what do I do?, Fair winds. Nasca, C. P & Pastides, H. (2001). Fundamentals of Cancer epidemiology, Jones and Barlett learning. Rosenblatt, A & Guidi, H. G. C. (2009). Human Papilloma virus: A practical guide for urologists, Springer. “Sexually Transmitted Diseases” (2011). Centre for Disease Control and Prevention. Retrieved from: http://www.cdc.gov/std/hpv/stdfact-hpv-vaccine-young- women.htm Steben, M., and Duarte Franco, E. (2007). Human Papilloma virus infection: Epidemiology and Pathophysiology, Gynecologic oncology, 107: S2- S5. Weaver, B. A. (2006). Epidemiology and Natural History of Genital Human Papillomavirus Infection, The Journal of American Osteopathic Association, 106 (1): S2- S8. “WHO Information Centre on Human Papilloma Virus and Cervical Cancer”. (2008). World Health Organization. Retrieved from: http://www.who.int/hpvcentre/statistics/en/ Read More