HPV Infection and Associated Cancers

HPV Infection and Associated Cancers 1.0 Introduction Human papillomavirus (HPV) is a sexually transmitted virus that is spread through genital and skin-to-skin contact [1]. Its infection is the most common sexually transmitted infection in the world [1] and accounts for 561200 representing 5.2% of all cancer cases worldwide [2, 3]. Over 290 million HPV infections are recorded worldwide annually [4] and the prevalence of HPV vary from 14% to over 90% [5]. Currently, over 170 HPV-types have been identified and designated with numbers [6-8] and at least forty are transmitted through genital contact [9]. The virus can also be transmitted through skin-to-skin sexual contact (regardless of penetration), mucous membranes or bodily fluids, oral sex and mutual masturbation (genital fondling) [10]. HPV affects only humans [11]. When the HPV virus comes in contact with human cells, it may bring about changes to the cell called lesions which may lead to the development of tumors [6]. High-risk HPV-types (hrHPV) (aka oncogenic HPV-types) are able t o incorporate themselves into the cell DNA and transform its behavior in a way that results in cancer whereas low-risk HPV-types (aka non-oncogenic HPV-types) do not cause cancer [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 activity (HITCH) cohort study reported an HPV infection of more than 56% in young adults in relatively new sexual relationships and more than half (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% occurred 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% amongst studies of multiple 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 person 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 flat or even shaped-like-a-cauliflower bumps or groups of bumps around the genital region) [9] and precancerous lesions [15]. While HPV-1/2 causes common warts (usually found 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 other sites on the respiratory tract) [17, 18]. These warts recur very often and obstruct breathing [17]. Another major symptom of HPV infection is that it is strongly related to cancer, specifically cancer of the cervix, vagina, vulva, oropharynx, anus and penis [2, 3] (For details refer to Section 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 section 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 particularly important as a clear inclusion or exclusion criteria is set for cancers of the cervix, 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 six cancers. In these subsections, actual definitions of cancer of the cervix, vagina, vulva, anus and penis will be provided as well 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 incidence rates of these HPV-associated cancers. Section 1.3 will disc uss 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 Cancers When most people think of an HPV infection, they might think of cervical cancer. However, one must be careful because they is a growing subset of non-cervical cancers extensively established as strongly linked to HPV infection and the proportion of these cancers vary by anatomical site [3]. These cancers include 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 penile cancers and 90%-93% of anal cancers [3, 20] and 100% of cervical cancer cases are attributable to HPV [21]. The difference in HPV-attributable proportions for these non-cervical cancers partly results from inherent differences in the methods of detecting cancer, differences in geographic locations in HPV-attributable populations [22]. Other potential reasons for differences in HPV proportions are because som e studies report on individuals currently having a detectable infection while others report on individuals who have 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 assumed to have an analogous incidence distribution as anal cancer. Cancer-based registries (CBRs) identify 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 and 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, penile, vaginal, vulvar and oropharynx are discussed next in subsections 1.11 to 1.16. 1.11 Cervical Cancer Cervical cancer is a major global public 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 zone [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]. Before 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 regresses into the endocervix with increasing age 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]. Adenoc arcinoma (AC) and adenosquamous carcinoma (ASC) are the next common types while neuroendocrine or small cell carcinomas, primary cervical lymphoma, cervical sarcoma, and rhabdomyosarcoma are rare [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 100000 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 cervical cancer of more than 50 per 100000 women [28]. In contrasts, cervical cancer rates are generally less than 7 per 100000 women in western 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 screening programs [28]. Comprehensive national screening programs for cervical cancer and dysplasia have a great impact in managing cervical cancer incidence [35]. The Papanicolaou (pap) smear screening test, which detects cytological abnormalities of the cervical transformation zone reduced cervical cancer incidence by more than 70% in developed countries [36]. Risk 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 women [41]. Cervical cancer is preventable by avoiding HPV, the causative agent or through the identification and treatment or pre-invasive 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-grade 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 Cancer Anal 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 continuous 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 Cancer Another rare malignancy associated with HPV infection is penile cancer. It accounts for less than 1% of all male cancers [3, 43 and 52]. It is an abnormal growth found in the tissues 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 histological types of different growth patterns, clinical aggressiveness and HPV association 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-à  -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 penile 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 essentially 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 generally reported in men with low socioeconomic status [52]. Smoking is also an independent risk factor associated with penile cancer [62, 63]. Though not an Acquired Immune 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 retract the foreskin) [62]. 1.14 Vaginal Cancer HPV-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

Macbeth vs the Godfather Essay

The change from good to evil can happen to anyone. It can happen to the best of people, just like Macbeth in William Shakespeare’s Macbeth and Michael Corleone in Francis Ford Copalla’s the Godfather. In these two completely different stories, the protagonists Macbeth and Michael Corleone, start off good and transition into evil and gain too much power for them to handle. Changing isn’t a choice for either of them and evil just presented itself upon them. In both the Godfather and Macbeth, the change of the protagonist from good to evil is in complete plain sight; however, the protagonists themselves do not see or sense the change. In the Godfather, the protagonist Michael Corleone changes rapidly from god to evil without even a bit of realization what he is getting himself into, some may say that he is the new godfather. As soon as the original godfather (Michael’s dad) was put into the hospital, Michael didn’t even know until days later, he had to find out through a newspaper, this shows how uninvolved Michael is with his family. When he goes to visit the family, he takes over immediately. As soon as he takes over he already is planning to kill someone and he has never killed anyone before, by the end of the movie, he is already lying to his wife about him not killing someone because he has now been transferred into a true Corleone and made his transition from good to evil. In Macbeth, the protagonist Macbeth eases into his transition from good to evil a little more smoothly and a little more hesitant. Macbeth debates killing Duncan because he is his follower, when he is talking about it with his wife Lady Macbeth she calls him a coward for not helps frame some of the innocent drunks from the night before, when she says â€Å"a little water will clear us of this deed.† She is saying the water will wash away their guilt and consciences. When Macbeth becomes king he gains too much power and has too much self-confidence because the witches have told him â€Å"Macbeth cannot be killed by anyone born of woman.† He now has way too much power and becomes mad with it, the thought of killing Duncan has made Lady Macbeth crazy. The comparison between Macbeth and Michael Corleone is a strangely different but similar situation because they have both started out good with no evil thoughts or intentions at all, and then throughout each of the stories, Macbeth and Michael Corleone both become evil without realizing the power that the each of them have, they have both transitioned in completely different ways but they ended up in the same ending situation.

Questions On Issues Of Abortion - 1355 Words

Wallace 1 Blayk Wallace Ms Blevins Period 3 English 12 Issues of Abortion Abortion has became a big issue in not just the US but in pretty much everywhere else around the globe. To some people it is a sin to do but to others they might have a good reason to go through it but it can be just an easy way out of going through pregnancy and raising a child. Abortion should only be legal under certain circumstances by applying equality amongst the fetus and the mother without giving more rights to either for example if the mother was raped ,while possibly being underage as well, if something is wrong with her like if she was in danger of dying , or if something is wrong with the fetus like a sever disease then the mother should have a saying if she wants to have an abortion but if none of those reasons apply then the woman should go through the pregnancy if it doesn t harm her. The main problem with abortion is the fact that it has to do with a person s life being taken away. 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Corporate Responsibility And Marketing Strategies

Assignment 1: Corporate Responsibility and Marketing Strategies Examine Apple’s Current Position on the Company’s Ethical and Social Responsibilities, and Determine Whether or Not the Company Has Met These Responsibilities. Provide Two (2) Examples That Support Your Position Social and ethical responsibility of a company is that it will use all its resources in a way that will not affect the people and societies physically or socially. It is moral duty of businesses that they should take care of environment and people from whom they are running their business and generating profits. Social responsibility covers all the stakeholders of company. For example employees, customers, social groups, shareholders etc. Apple is one of the leading technology companies in the World. Apple has shown its concern for societies and environment. It is the first technology company who joined Fair Labor Association (FLA) and volunteers itself for an unprecedented audit. Management of Apple ensures that all of their production processes are according to the laws and regulation of local as well as international laws. Apple asserts a code of ethics and standards for their suppliers and ensures that their suppliers fulfill the standards of Apple (McKenzie, 2012). They have implemented extensive staff training programs not only for their workers but also for the suppliers and assisting them in improving their processes and technology. Determine the Impact That the Publication of Ethics and SocialShow MoreRelatedCorporate Responsibility and Marketing Strategies1838 Words   |  8 Pagesï » ¿ Corporate Responsibility and Marketing Strategies Wanda Joyce McGhee Dr. Malinda Swigart Business 508 July 13, 2014 Corporate Responsibility and Marketing Strategies There is no question that Apple is a remarkable company. 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In addition to its business turnaround, its innovative design, and its media content and apps, the unadulterated sexiness of all its products makes Apple hard to resist. For me, what isn’t hard to resist, is asking: How can a company that is this extraordinary in other respects be missing in action on corporate social responsibility? Apple’s Supplier Responsibility Report reveals that the company is taking action to stop unethical practices among its suppliers. These have included use of†¦show more content†¦Apple conducted 33 specialized audits at facilities employing migrant workers who may be at risk for unfair treatment. Apple required suppliers to reimburse US$3.9 million in excess foreign contract worker fees, it was confirmed, in January, 2014 that all active third-party auditors verified identified tantalum smelters in Apple’s supply chain as conflict-free (Forbs, 2014). Apple’s position on climate change is also a work in progress. Apple is working to improve its position in the world on climate change. Apple says it wants to leave the world better than they found it. Apple strives to create products that are the best they can be in every way. Products that is beautiful, easy to use and powerful. Apples passion for innovation goes into to how Apple thinks about its social responsibility of being environmentally responsible. Apple works tireless on reducing its impact on climate change by finding ways to use greener materials, and conserve the resources we all need to thrive. The Impact of Publications of Ethics and Social Responsibility on Apples Reputation Apple’s reputation was challenged by the impact of the publications of ethics and social responsibility violations made by suppliers. 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The term CSR refers to a company?s obligation to maximize its positive impact on society, accommodating changing social, market stakeholder pressures in an effort to achieve Corporate Responsibility And Marketing Strategies Corporate Responsibility and Marketing Strategies Wanda Lassiter Strayer University BUS 508 July 19, 2015 Revised date: August 12, 2015 Apples current position on the company ethical and social responsibilities, and determine whether or not the company has met these responsibilities Apple corporation’s current position in the company overall ethical and social responsibilities have been met over the years because (Internet, 2015), Apple has become one the most iconic brands in the world. It stands for innovation in its technology, design and product experience. At the same time, like its peers and competitors in the consumer electronics industry, it faces tough issues around labor and human rights in its relationships†¦show more content†¦According to Transparency International, and NGO that monitors and publicizes information on the transparency of corporate and political bodies, Apple ranks as the least transparent company amongst the most valuable multinational corporations in its Transparency in Corporation Reporting index. Many of Apple’s secretive practices involve its supplier’s. Campuses where Apple products are made are gated off and do not allow entry to the public. Security guards and local police are employed to prevent trespassing at these facilities. Factory workers are required to sign confidentiality agreement and live in dormitories within the factory campuses. This high level of secrecy makes it difficult for outsiders, including third-party whistleblowers to become aware of the conditions within Apples’ suppliers factories. If Apple is serious about becoming a socially responsible corporation, it must end its secretive practices that prevent the public from observing is business practices and the working conditions within its supplier’s factories. More public access to Apple and its suppliers’ facilities should be permitted. Terms within their confidentiality agreements should be