HPV Infection and Associated Cancers

HPV Infection and Associated pubic louses1.0 IntroductionHuman papillomavirus (HPV) is a sexu solelyy genetic virus that is spread through and through genital and skin-to-skin contact 1. Its transmitting is the or so greens sexu altogethery familial infection in the world 1 and accounts for 561200 representing 5.2% of on the whole undersurfacecer cases ecu custodyic 2, 3. Over 290 million HPV infections argon recorded worldwide annually 4 and the prevalence of HPV vary from 14% to all over 90% 5. Currently, over 170 HPV-types learn been identified and designated with numbers 6-8 and at least 40 atomic number 18 transmitted through genital contact 9. The virus can besides be transmitted through skin-to-skin sexual contact (regardless of penetration), mucose membranes or bodily fluids, oral sex and mutual masturbation (genital fondling) 10. HPV affects sole(prenominal) humans 11. When the HPV virus comes in contact with human cells, it may perplex rough changes t o the cell called lesions which may lead to the develop manpowert of tumors 6. High-risk HPV-types (hrHPV) (aka oncogenic HPV-types) are able to incorporate themselves into the cell DNA and transform its behavior in a way that results in crabby person whereas low-risk HPV-types (aka non-oncogenic HPV-types) do not precedent crab louse 10.HPV infection is most common in young men and women in their teens and early 20s 11. Authors of the HPV Infection and Transmission among Couples through Heterosexual practise (HITCH) cohort study report an HPV infection of to a greater extent than 56% in young adults in relatively new sexual alliances and more than half(prenominal) (44%) were infected with oncogenic HPV-types. In the early 2000s, about 6.2 million new cases of HPV infection were recorded in America of which 74% bechancered in 15 to 24-year olds 12. A systematic review of more than 40 studies by Dunne et al (2006) showed that HPV prevalence estimates vary from 1.3% to 72.9% a mongst studies of quintuple sites and 56% of them reported a prevalence of more than 20% 13.Most HPV infections are asymptomatic and usually resolve on their own over the course of weeks 14. For example, HPV-5 may cause infections that may linger for a very long time in an infected individual without showing any clinical symptoms 9. However, when an HPV infection does not resolve naturally, it may result in malignancies including genital warts (small or large, raised or horizontal or even shaped-like-a-cauliflower bumps or groups of bumps round the genital sphere) 9 and pre crabmeatous lesions 15. firearm HPV-1/2 causes common warts (usually comprise on the hands, feet and sometimes knees and elbows), HPV-6/11 causes recursive Respiratory Papillomatosis (RRP) (when warts are formed on the larynx 16 or opposite sites on the respiratory tract) 17, 18. These warts recur very very much and obstruct eupnoeic 17. other major symptom of HPV infection is that it is strongly relat ed to pubic louse, specifically crabmeat of the neck, vagina, vulva, oropharynx, anus and penis 2, 3 (For details refer to variancealization 1.1). One common feature of these cancers involves the transmission of HPV infection to the stratified epithelial tissue (a multilayered cell with every cell in direct contact with a basement membrane that separates it from a connective underlying tissue) 2, 14 -15.The first separate of this chapter of this thesis, section 1.1, briefly introduces all cancers associated with and attributable to HPV infection as reported in 2, 3. Definition of HPV-associated and HPV-attributable cancers are also given in the same section. This is peculiar(a)ly important as a clear inclusion or exclusion criteria is set for cancers of the neck opening, vagina, vulva, anus and penis as defined by their causal methods which are HPV-inspired or otherwise. Subsections 1.11 to 1.16 are devoted to respectively discussing all half a dozen cancers. In these s ubsections, actual definitions of cancer of the cervix, vagina, vulva, anus and penis will be provided as headspring as their composition by specific anatomical region. The relationship between HPV and these cancers will also be provided in these subsections as well as a brief history. Section 1.2 will provide a detailed discussion regarding international trends in the relative incidence rates of these HPV-associated cancers. Section 1.3 will discuss the behavior of the incidence rates in Canada as established in Canadian literature and will, therefore, show why this thesis seeks to explore the behavior of incidence rates of HPV-associated cancers in Canada using Canada-wide data. Finally, section 1.4 will itemize the research questions in this thesis.1.1 HPV-associated malignant neoplastic diseasesWhen most people commend of an HPV infection, they might think of cervical cancer. However, one must be close because they is a growing subset of non-cervical cancers extensively esta blished as strongly tie in to HPV infection and the proportion of these cancers vary by anatomical site 3. These cancers take on cancer of the oropharynx as well as those in the genital region (i. e. vagina, anus, vulva and penis) 19. Current data reveal that HPV-infection is associated with 12%-63% of oropharyngeal cancers, 40%-64% of vaginal cancers, 40%-51% of vulvar cancers, 36%-40% of penial cancers and 90%-93% of anal retentive cancers 3, 20 and ascorbic acid% of cervical cancer cases are attributable to HPV 21. The difference in HPV-attributable proportions for these non-cervical cancers partially results from inherent differences in the methods of detecting cancer, differences in geographic locations in HPV-attributable populations 22. new(prenominal) potential reasons for differences in HPV proportions are because some studies report on individuals presently having a detectable infection while others report on individuals who gift ever had a detectable infection and also there are differences in the HPV strain tested for by different studies 23.An HPV-associated cancer is a specific cellular type of cancer that is diagnosed in a particular part of the human body where HPV is found 9. The virus is often found in the vulva, vagina, cervix, rectum, anus and oropharynx 23, 24. Several studies including 24 have shown that the incidence rates of HPV-associated anal and rectal cancers are similar, so from-here-on-in, rectal cancer will be delusive to have an analogous incidence distribution as anal cancer. Cancer-based registries (CBRs) find diagnosed cases by using the International Classification of Diseases for Oncology, 3rd revision (ICD-O-3) codes for HPV-associated groups cancers of the anus (C20-C21), vulva (C51), vagina (C52), cervix (C53), penis (C60) and oropharynx (C019, C024, C028, C090-C099, C102, C108, C140, C142 and C148) 25, 26.An HPV-attributable cancer is a cancer that is possibly caused by HPV 9. HPV causes all cervical cancers an d cancers of the vulva, penis, vagina, anus, rectum and oropharynx as shown above.The epidemiology and histology of HPV-associated cancers of the cervix, anal, penial, vaginal, vulvar and oropharynx are discussed next in subsections 1.11 to 1.16.1.11 cervical Cancercervical cancer is a major global reality health threat it is the fourth most prevalent cancer in women, with approximately 500000 new cases annually 27, 28. Almost all cervical cancers occur at the junction of the endocervix and the ectocervix, at a junction called the transformation govern 28, 29. According to the International Federation of Gynecology and Obstetrics (FIGO), any vaginal lesion that relates to the ectocervix should also be treated as cervical cancer 29. ahead puberty, this junction is found on the visible vaginal portion of the cervix (i.e. the ectocervix) and is fairly stable 30. Within young women as well as women on oral contraceptives, the visible transformation zone is called ectopy, which regres ses into the endocervix with increasing geezerhood and the commencement of sexual intercourse 31. The main morphological type of cervical cancer associated with HPV is squamous cell carcinoma (SCC) which accounts for about 60% of all cervical cancer cases 28. Adenocarcinoma (AC) and adenosquamous carcinoma (ASC) are the next common types while neuroendocrine or small cell carcinomas, primary cervical lymphoma, cervical sarcoma, and rhabdomyosarcoma are obsolescent 28.There are geographical differences in the cervical cancer incidence rates 28. GLOBOCAN 2012 examined the burden of cervical cancer amongst countries by estimating age-standardized incidence rates (ASR) by country, and a global ASR of 14 per hundred thousand women of all ages was reported 32. Over 85% of the global burden of cervical cancer occurs in developing countries, where it accounts for 13% of all female cancers 33, 34. Most countries in South America and sub-Saharan Africa report an ASR associated with cervica l cancer of more than 50 per 100000 women 28. In contrasts, cervical cancer rates are generally less than 7 per 100000 women in horse opera Europe, western Asia, New Zealand, the Middle East and Australia and these geographical differences in cervical cancer incidence rates closely reflect the availability of cervical precancer back programs 28.Comprehensive national screening programs for cervical cancer and dysplasia have a great impact in managing cervical cancer incidence 35. The Papanicolaou (pap) stigma screening test, which detects cytological insaneities of the cervical transformation zone reduced cervical cancer incidence by more than 70% in certain countries 36. assay factors associated with cervical cancer include early sexual debut, multiple sexual partners 37, smoking 38, a history of sexually transmitted diseases (STDs) 39 and chronic immunosuppression with Human Immunodeficiency Virus (HIV) infection 40. Circumcision of male sexual partners is protective for wo men 41.Cervical cancer is preventable by avoiding HPV, the causative agent or through the identification and treatment or pre- invading lesions by histopathologists 30. These precursor lesions to cervical cancer are called cervical intraepithelial neoplasia (CIN) or, specifically, squamous intraepithelial lesions (SIL) a term used to identify where abnormal cells develop 30. Lesions from Low- chassis CIN mostly relapse while those of high grade require comprehensive treatment 42. For high-grade CIN, the rate of progression to invasive cancer if left untreated is approximately 30%-50% with 30 years, however, proper treatment drastically reduces this risk to under 1% 42.1.12 Anal CancerAnal cancer or squamous carcinoma of the anus and anal canal is a rare malignancy accounting for only 2% of all gastrointestinal cancers 43, 44 and about 4% of cancers associated with the lower gastrointestinal tract 45. Anal cancers emerge from anal mucosa when glandular elements associated with the gastrointestinal tract develops into squamous mucosa 28. Research has shown that a greater proportion of anal cancer cases are attributable to invariable infection with hr-HPV (HPV-16/18) 46. The global ASR associated with anal cancer is shown to be 1.0 per 100000 32.Risk factors for HPV-associated cancer of the anus are generally associated with sexual activity 46, 47. Reporting at least 10 sexual partners in ones lifetime increases the risk of developing anal cancer 48. Elsewhere, receptive anal intercourse with two or more partners and HIV infection 49, a history of sexually transmitted infections (STIs) (e.g. gonorrhea, chlamydia trachomatis, herpes simplex virus 2) 48, genital warts 50 and smoking 51 have also been shown to increase the risk of developing HPV-associated anal cancer.1.13 Penile CancerAnother rare malignancy associated with HPV infection is penial cancer. It accounts for less than 1% of all male cancers 3, 43 and 52. It is an abnormal growth found in the tissu es or on the skin of the penis and about 95% of all cases of penile cancer are SCC 53. It mostly results from a series of epithelial modifications (precursor lesions) which often progress quickly from low-grade lesions to high-grade lesions and finally invasive carcinoma 53. The frequency of SCC being preceded by premalignant lesions is still unknown 54-57. Although SCC is the most prevalent penile neoplasia, several histologic types of different growth patterns, clinical aggressiveness and HPV tie have been reported 58. An HPV infection is found in basaloid (warty penile SCCs (39%) and 76%, mixed warty-basaloid (82%) 55. DNA of HPV has also been identified in about of 30%-40% and about 70%-100% of invasive penile cancer tissues 54. Variations in histological subtypes of penile cancer vis--vis the rate of HPV-positivity is an indication that HPV may be a cofactor in the carcinogenesis of certain variants of penile SCC 59. This therefore points to higher incidence associated with pe nile cancer in regions with higher prevalence of HPV and vice versa 60.Geographical differences in study populations result in variations in incidence rates associated with penile cancer 32. In North America and Europe, SCC of the penis accounts for less than 1% of cancers associated with men 43. In developed countries, the ASR of penile cancer is between 0.1 and 0.5 per 100000 men 32. However, for developing countries including Malawi, Uganda, Brazil, Vietnam, Paraguay, Columbia and India, the penile cancer accounts for more than 10% of reported cancers 32. The associated ASR is at least 2.0 per 100000 men is reported in these countries 32, 43-44.The incidence of penile cancer suggests the presence of risk factors 28. Risk factors basically are associated with chronic inflammation and HPV infection, compromised genital hygiene 61-63. Circumcision is reported to have a 3-fold decrease in penile cancer risk 62. Cancer of the penis is classically associated with old age and is genera lly reported in men with low socioeconomic status 52. Smoking is also an free-living risk factor associated with penile cancer 62, 63. Though not an Acquired repellent Deficiency Syndrome (AIDS)-defining cancer, the risk of developing penile cancer in HIV-positive men is 8 times higher than in HIV-negative men. Men with penile cancer are most likely to report protracted penile rash, penile injury, prior history of genital warts and phimosis (the inability of an uncircumcised penis to fully resign the foreskin) 62.1.14 Vaginal CancerHPV-associated vaginal cancer is a rare malignancy with an ASR between 0.2 and 0.7 per 100000 in most countries 64. It is associated with older women, with incidence peaking around the sixth and seventh decades of life 65. Several studies have shown that