HPV has been found to increase risk for oropharangeal, penile and anal cancers in men, including both HIV-negative and HIV-positive GBT men. Chin-Hong et al. [9] found anal HPV infection in 57 % of a sample of urban HIV-negative men. Infection in this cohort was correlated with receptive anal intercourse and greater than five sex partners, both in the past 6 months. Rates of HPV among GBT men with HIV infection have been found to be as high as 93 %–97.9 % [10]. Two HPV types, HPV 16 and 18, are considered to carry the highest risk for cancer [11]. Reviewing incident cases of anal cancer among men from 2004 to 2007, CDC attributed 93 % to HPV infection and 87 % specifically to HPV 16 and 18 [12].

There are eight types of human herpesviruses including varicella/zoster (VZV/HH3), Epstein- Barr virus (EBV/HHV4), Cytomegalovirus (CMV/HHV-5) and Kaposi’s sarcoma herpesvirus (KSHV/HHV-8) [13]. HHVs are transmitted both sexually and non-sexually with evidence of sexual transmission for HH2, EBV, CMV and KSHV [14].

In 1994, Chang [15] found that human herpesvirus 8 (HHV-8) was the cause of Kaposi’s sarcoma. In one study, Del Mistro [16] compared rates of HHV-8 and HPV among three groups of PLWH–MSM, heterosexual men, and women, finding higher rates of both HHV-8 and HPV among gay and bisexual HIV+ men.

Epstein-Barr Virus (EBV) is another name for human herpesvirus 4 and one of the most common human viruses. Most people are infected in childhood and do not develop symptoms or have very minor symptoms [17]. EBV was identified over 40 years ago in a biopsy of Burkitt’s lymphoma, becoming the first infectious agent to be directly associated with a human cancer

18].While there is limited epidemiological data on rates of EBV infection in gay and bisexual men, one study found a higher prevalence of EBV type 2 among gay men compared to heterosexual men associated with HIV infection and a higher number of sexual partners [19]. Additional epidemiological research would be helpful to know more about prevalence rates of EBV among gay/bisexual/transgender and heterosexual men in a variety of geographic locations (unlike parts of Africa where EBV is endemic). EBV is associated with a diverse group of lymphomas and carcinomas including Burkitt’s lymphoma, Hodgkin’s disease, Post-transplant lymphoproliferative disease, AIDS- associated lymphoma, and nasopharyngeal and gastric carcinoma [17].

Hepatitis B and C are disproportionately found among gay and bisexual men [19]. Hepatitis B is spread in a manner similar to HIV, i.e. through blood or semen. Hepatitis B is considered to be 50–100 times more infectious than HIV [20]. Hepatitis C is primarily spread through sharing of needles and syringes. Over time, Hepatitis B and C attack the liver, causing a variety of liver diseases including liver cancer. It is estimated that 90 % of liver cancers in less developed countries and 40 % of liver cancers in more developed countries are attributable to HBV or HCV infection [22]. Approximately 20 % of gay and bisexual men account for new Hepatitis B infections [20], disproportional to their 4 % representation in the general population.

Robbins [25], exploring data from 1996 to 2010, looked at cancer trends for three ADCs and seven NADCs to see if demographic changes for HIV positive individuals, changes in relative risks, and/or background incidence in the general population had an effect, and if so which. Table 2.2 includes a summary of changes identified by Robbins. Simard [26] had similar findings looking at data from 1980 to 2006.

Each of the ADCs has a viral cause suggesting that the advent of HAART in 1996 has had an effect on cancer reduction by improving the immune system’s ability to manage the viral infection [25]. At the same time, demographic shifts were likely related to the increase in liver cancer and prostate cancer; specifically, the increase in liver cancer reflected additional years living with Hepatitis B and C viruses. Curtrell [27] explores several factors related to the increase in NADC including oncogenic effects of HIV, immunosuppression, chronic inflammation and immune activation, exposure to HAART, higher rates of oncogenic viral coinfections and traditional cancer risk factors. The same study found that when standard cancer therapy is given, PLWH have the same outcomes as the non-HIV population [27].

Other types of NADC have been identified among PLWH. Silverberg [28] compared a California cohort of HIV-infected persons, of whom 74 % were MSM, and compared them with a demographically similar group non-HIV-infected persons. He found adjusted rate ratios, coming HIV-infected with HIV-uninfected persons of 37.7 for ADC, 9.2 for infection-related NADC, and 1.3 for infection-unrelated NADC. The rates for individual NADC included anal squamous cell (rate ratio = 101.6), Hodgkin lymphoma (rate ratio = 19.4), penis (rate ratio = 5.8) liver (rate ratio = 2.7) and HPV-related oral squamous cell cancers (rate ratio = 2.0) [27]. Among infection- unrelated NADC there were increased rates for people with HIV infection for other anal (rate ratio = 35.3, nonmelanoma skin (rate ratio = 10.6), other head and neck (rate ration = 2.7), lung (rate ratio = 1.9) and melanoma (rate ratio = 1.5). HIV-infected persons also had a lower rate of prostate cancer (rate ratio = 0.7). HIV infection was not associated with higher rates of other infection-unrelated NADC [27]. Similarly, Grulich et al. [29] demonstrated that other cancers not known to be associated with an infection were also elevated in both immunosuppressed populations, that is, HIV-infected persons and transplant recipients, including lung and kidney cancers, multiple myeloma, and leukemia. Yanik [30] found decreasing rates from 2000 to 2011 of NHL among a cohort of HIV-infected individuals in North Carolina.

Silverberg [31] found that HIV-infected patients had a twofold higher incidence rate of non- melanoma skin cancers compared with non-HIV-infected subjects. Squamous cell cancers but not basal cell cancers were associated with immunodeficiency. Shebl [32] concluded that chronic pulmonary inflammation arising from infection contributes to recurrent pneumonia which puts PLWH at greater risk of lung cancer, independent of higher smoking rates. Similarly, Sigel [33] found HIV infection was an independent risk factor for lung cancer when controlling for potential confounders, including smoking and surveillance bias.

Persson [34] looked at data for 596,955 person with AIDS from 16 US population-based HIV/AIDS and cancer registries. Risk of stomach and esophageal malignancies in people with HIV/AIDS were compared with those of the general population using standardized incidence ratios (SIRs). People with HIV/AIDS had increased risk of carcinomas of the esophagus (SIR, 1.69) carcinoma of the stomach (SIR, 1.44), esophageal adenocarcinoma (SIR, 1.91), squamous cell carcinoma (SIR, 1.47), and carcinomas of the gastric cardia (SIR, 1.36) and noncardia (SIR, 1.53) compared with the general population. Rates of NHL decreased from 1980 to 2007 with HAART, but incidence of carcinomas remained consistent over time [34].

Thus while HAART has reduced the risk of cancer related to HIV and EBV i.e. NHL, other cancer risks continue to be elevated related to HIV infection and immunologic status, possibly unrelated to other infections.

Incident anal cancer has increased by 96 % in men and 39 % in women since the 1980 primarily due to the HIV epidemic [37]. Nearly all anal cancers in gay and bisexual men are associated with HPV [38]. The rate of abnormal anal cytology in a cohort of 60 young gay and bisexual men (mean age = 21.2 years) was found to be comparable to the rate among adult MSM [39]. Increased risk for developing anal cancer among PLWH was associated with prolonged survival and increasing immunosuppression [40].

The prevalence of cirrhosis and hepatocellular carcinoma in patients with human immunodeficiency virus infection. The Hepatitis C (HCV) epidemic has driven up the rate of cirrhosis and hepatocellular carcinoma (HCC) amongst HIV-infected persons. Among patients co-infected with HIV and HCV, there was a dramatic increase in the prevalence of cirrhosis (3.5–13.2 %), decompensated cirrhosis (1.9–5.8 %), and HCC (0.07–1.6 %). Little increase was observed among patients without HCV co-infection in the prevalence of cirrhosis [41].

Interventions to reduce STIs including HIV include behavioral interventions, use of highly active antiretroviral therapy (HAART), and both HPV and HBV vaccines, screening, and treatment, are frequently targeted to gay and bisexual men. In many situations, people with any STIs are recommended to undergo the same cancer screening and, if diagnosed, receive the same treatment regimens for both the infection and the cancer as those without infection. However this is not always the case, and there are many studies in progress to find more effective ways of treating these populations.

Gilbert [44] found there not to be much of a difference between HIV(+) and (−) men, but that overall there was acceptability for the vaccine, little understanding of how HIV increases risk for HPV-related diseases, and other misperceptions about the vaccines. This information can inform awareness/prevention efforts for gay men. Blackwell [45] conducted a descriptive study to assess knowledge of HPV, anorectal carcinoma, and anorectal screening in a sample of MSM in Orlando, FL. The 89 participants demonstrated low levels of knowledge with an average score on knowledge items of 38 % correct. Of the 49 participants who had heard of anal Papanicolau (Pap) smears, only five (10.2 %) discussed screening with a physician, while eight (16.3 %) had discussed it with a nurse, and 16 (32.7 %) with another health care professional.

Rosa-Cunha [46] found that only 54 % of men who have sex with men (MSM) reported discussing anal health with their HIV providers in the prior 12 months. Rates for MSM and heterosexual men were 5.56 times and 2.31 times more likely, respectively, than women to have to discuss anal health with their HIV provider. Interestingly, having reported unprotected sex with a partner who was HIV negative or whose HIV status was unknown was inversely related to having a discussion about anal health with their primary care provider [46].

Burkhalter [47] explored perceived risk of cancer in a large urban community center and found that men associated a higher number of sexual partners with a higher risk for cancer. Sanchez [48] found that a quarter of MSM attending a sexually transmitted disease clinic in New York City did not know that HPV is transmitted through anal sex and 77 % were unaware of the link between HPV and anal cancer.

Vaccinations are available to reduce exposure to HPV and Hep B. In 2009, the FDA licensed the use of quadrivalent vaccine for the prevention of genital warts in males ages 9–26 and in 2010, its use was extended for prevention of anal cancer in the same group [49]. On October 25, 2011, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of quadrivalent HPV vaccine in males aged 11–12 and vaccination with HPV4 for males aged 13–21 who have not been previously vaccinated or did not complete the three dose series [50]. Males aged 22–26 may also be vaccinated [50]. To date, update of HPV vaccination among adolescent males generally has been limited. Reiter [51], looking at a nationally representative sample of adolescents, found that HPV vaccine initiation among males ages 13–17 increased from 1.4 % in 2010 to 8.3 % in 2011. Parents were more likely to get their sons vaccinated against HPV if they received a recommendation from their healthcare provider [51]. Gay and bisexual men have been found to have greater willingness to receive HPV vaccines as well as higher levels of concern about HPV-related diseases [52].

For GBT males, perceived benefits and barriers were the most proximate predictors of intention to be vaccinated against HPV, while knowledge and perceived threat exerted an indirect influence [53]. One study found 73 % of gay and bisexual men were willing to receive the HPV vaccine [52]. Another study of young gay and bisexual men found that 36 % were likely to be vaccinated based upon perceived stronger physical and psychological benefits [54]. Kim [55] found HPV vaccination to be cost effective using the standard measure of costs per QALY below $ 50,000. With respect to Hepatitis B vaccination, a study of 3,432 MSM age 15–22, found only 9 % immunization coverage and 11 % infection rates [56].

Given the increasing rates of anal cancer, substantial effort has been placed on screening for anal intraephitelial neoplasia (AIN), primarily using high-resolution anoscopy. High resolution anoscopy (HRA) was developed in England in the 1980s and uses a colposcope to explore the anal mucosa. A swab, soaked in 5 % acetic acid, is inserted through the anoscope and applied topically for 1–2 min. Lesions reacting to the application are identified and biopsied [57]. Anal-rectal cytology collects non-gynecological specimens via exfoliative cytology tests which are then interpreted by a qualified pathologist. The smear is the same technique as a Pap test, whereby the exfoliated cells are quickly smeared and fixed onto a glass slide [58]. Cachay [59] found that despite the availability of several modalities for treatment of precursors of anal cancer, evidence that current treatment modalities favorably alter the natural history of human papillomavirus oncogenesis in the anal and perianal regions is still inconclusive. However, there is sufficient evidence to state that the accuracy of anal cancer screening procedures (cytology and high-resolution anoscopy directed biopsy) is comparable to the accuracy of those used in screening for cervical cancer precursors. More research is needed to assess the efficacy of anal cancer screening programs on reducing morbidity/mortality in the HIV-infect population [59].

Darragh [60] looked at inter-rater reliability in the reading of Papanicolaou-stained liquid based cytology cells being used for anal cancer screening among high risk populations of gay and bisexual men. Two observers had an overall agreement of 66 % and this increased to 86 % for dichotomized cytology results. Thus reviewers were able to detect which lesions were precancerous and which were not, similar to the methodology used for cervical cancer screening. A high rate of acceptability of screening was found at a Veteran’s Affairs HIV Clinic [61]. When approached during a routine care visit to participate in the study by obtaining an anal Pap smear, 82 % of HIV-patients agreed to do so. Another clinic was established at an HIV clinic in New York to comply with New York State AIDS Institute guidelines for anal cancer screening and treatment in HIV-positive persons. The intent is to reduce morbidity and mortality in young, HIV-infected persons [62].

However, a review of the literature found that screening for anal cancer in HIV-positive gay and bisexual men as well as HIV-positive women was not cost-effective [63]. Given the number of false-positives, results with treatment for high-grade AIN, there were no models that showed a 50 %

probability of cost-effectiveness to a quality-adjusted life year (QALY) gained reaching the value of 50,000 British pounds. This is contrary to earlier reports that found it to be cost effective to screen for anal squamous interepithelial lesions in gay and bisexual HIV-infected men [64].

Routine HIV testing, in the form of standard “opt-out” protocols is recommended by the CDC in all health care settings. This has not been widely implemented, but should be for cancer patients [65], in order to maximize effective HIV management during cancer treatment and improve clinical outcomes.

A review of recently published literature on the heightened risk for cancer in PLWH explored whether early HAART treatment can lower their risk [66]. The findings were that immunodeficiency still appears to be the key factor; however, there is emerging evidence that HIV may have direct oncogenic effects through inflammation and coagulation that HAART only partly normalizes. Analysis of studies comparing the impact of early versus delayed HAART was inconclusive [66]. Chiao [67] looked at a cohort of US veterans with HIV and in a multivariate analysis found that those with controlled (i.e. undetectable) viral load at 61–100 % of follow-up time had significantly decreased risk of squamous cell anal cancer compared to those with undetectable viral load less than 20 % of the time.