Incidence Of Anal Intraepithelial Neoplasia Research Articles

Efficacy, immunogenicity, and safety of a quadrivalent HPV vaccine in men: results of an open-label, long-term extension of a randomised, placebo-controlled, phase 3 trial

The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16-26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16-23 years) or men who have sex with men (MSM; aged 16-26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov, NCT00090285. Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1-11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0-6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0-8·7) versus 137·3 (83·9-212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0-7·7) versus 140·4 (89·0-210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5-114·4) versus 906·2 (553·5-1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6-212·3] vs 0 cases per 10 000 person-years [0·0-13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0-215·7] vs 0 cases per 10 000 person-years [0·0-10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9-1289·1] vs 101·3 cases per 10 000 person-years [32·9-236·3]). No vaccine-related serious adverse events were reported. The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. Merck Sharp & Dohme.

HIV-Associated Anal Cancer.

Anal cancer, despite being a rare malignancy, is increasing in incidence, accounting for 0.5% of all new cancer cases in the United States, with rate of new cases being 1.9 per 100,000 men and women. It is common in immunocompromised individuals, especially those with malignancy, human immunodeficiency virus (HIV) and human papillomavirus (HPV) infection. Despite similar treatment of anal cancer in both HIV-positive and negative patients, guidelines for prevention and treatment of therapy-related side effects are rarely studied. While these patients have a better prognosis on HAART, limited guidelines exist regarding appropriate therapy. There is a common link between HPV and HIV and the transmission of one is associated with increased risk of transmission of the other. HPV vaccine which is known to prevent high-grade cervical intraepithelial neoplasia is thought to also decrease the incidence of anal intraepithelial neoplasia. The association of HPV vaccine in the prevention of anal cancer in high-risk groups with HIV is a scarcely studied subject that requires further research.

Anal intraepithelial neoplasia: diagnosis, screening, and treatment.

Anal intraepithelial neoplasia (AIN) is a premalignant lesion for anal cancer. It is more commonly found in high-risk patients (e.g., human papilloma virus (HPV)/human immunodeficiency virus infections, post-organ transplantation patients, and men who have sex with men) and development is driven by HPV infection. The incidence of AIN is difficult to estimate, but is heavily skewed by preexisting conditions, particularly in high-risk populations. The diagnosis is made from cytology or biopsy during routine examinations, and can be performed at a primary care provider’s office. A pathologist can then review and classify cells, based on nucleus-to-cytoplasm ratios. The classification of low or high grade can better predict progression from AIN to anal cancer. There is little debate that AIN can develop into anal cancer, and the main rationale for treatment is to delay the progression. Significant controversy remains regarding screening, surveillance, and treatment for AIN. Management options are separated into surveillance (watchful waiting) and interventional strategies. Emerging data suggest that close patient follow up with a combination of ablative and topical treatments may offer the greatest benefit. HPV vaccination offers a unique treatment prior to HPV infection and the subsequent development of AIN, but its use after the development of AIN is limited. Ablative treatment includes excision, fulguration, and laser therapy.

Multidisciplinary Approach to the Management and Treatment of Anal Dysplasia.

The incidence of anal intraepithelial neoplasia (AIN) has been increasing over the years. AIN acts as a precursor lesion for anal squamous cell cancer. Factors leading to progression of AIN into malignancy are complex and involve grade of the lesion, human papillomavirus and HIV coinfection, as well as patient-related risk factors such as immunocompromised state and men who have sex with men. The multifaced aspects of this disease make its management challenging, as it involves several disciplines including pathology, primary care, infectious disease, and colorectal specialties. Each of these fields brings its own expertize to the management of AIN, and their collaborative, coordinated work culminates into best practice and optimized outcomes in the care of the AIN patient.

Virological and EpidEmiological aspEcts of anal carcinoma: currEnt and futurE challEngEs

Human papillomavirus infection, a sexually transmitted disease studied mainly in women due to its link to uterine cervical carcinoma, has become a health problem in men also, mainly by the significant increase of the prevalence and incidence of anal intraepithelial neoplasia and anal carcinoma in specific groups, such as men who have sex with men, HIV- seropositive and immunocompromised. The anal carcinoma, as cervical cancer, is associated with highrisk oncogenic HPV in 90% of cases, with HPV 16 as the predominant, followed by HPV 18. This fact occurs in a moment when there are no management protocols for HPV infection in the anal area, either preventive, diagnostic or therapeutic, and without an unique specialty that embraces the problem of HPV anogenital infection in men as does the gynecology for women, causing a dispersion of expertise. Added to this, there are still many doubts in the medical and general population about prophylactic vaccination for HPV in boys, and the absence of its distribution in a public health scale in most countries that still wait for statistical calculations to justify its use.

24. Successful treatment of anal intraepithelial neoplasia by CO2 laser in a sexual health service

Background Treatments for anal intraepithelial neoplasia (AIN) are still being established. Methods: An audit of patients referred for treatment of anal disease by CO2 laser at a Perth SHS was performed. Patient demographics including sex, sexual preference, age, and HIV status were documented. Anal cytology, histopathology, and HPV testing before and after treatment were reviewed in this preliminary analysis. Initial diagnosis of anal disease including AIN was made by high-resolution anoscopy (HRA) and by histological examination. Patients were then referred for treatment. Six-monthly HRA review occurred after treatment and the original site of HGAIN was biopsied. Results: Preliminary analysis of 28 patients included 16 patients with AIN 2 and 12 with AIN 3. After laser treatment, 7 patients had no AIN, 3 had AIN 1, 10 had AIN 2 and 4 had AIN 3, indicating successful reduction in AIN status (Pearson χ2 = 15.2, P = 0.002). The incidence of AIN decreased over the 18 months of follow-up. Conclusions: Studies of CO2 laser ablation of the anal canal are ongoing and need further study. Table 1. High-resolution anoscopy follow up Rx, treatment

Use of Highly Active Antiretroviral Therapy Is Associated With Lower Prevalence of Anal Intraepithelial Neoplastic Lesions and Lower Prevalence of Human Papillomavirus in HIV-Infected Men Who Have Sex With Men

The incidence of anal intraepithelial neoplasia (AIN) and anal cancer is increased in HIV-positive men who have sex with men (MSM). Persistent high-risk human papillomavirus (HPV) infection is an important etiologic agent. In this study, a group of 250 HIV-positive MSM was included to determine the prevalence of AIN and to investigate the role of highly active antiretroviral therapy (HAART), high-risk HPV, and other risk factors possibly associated with this prevalence. Among patients included, 108 (43.2%) had lesions suspicious for AIN. Histologic analyses showed AIN 1 in 24 patients (22.2%), AIN 2 in 6 patients (5.6%), and AIN 3 in 10 patients (9.3%). In multivariable analyses, the use of HAART was associated with the absence of AIN (P = 0.045). In MSM without HAART, HPV infection was detected significantly more often compared with those who used HAART (P = 0.010). AIN was associated with HPV types 16 and 6. In this cross-sectional study in 250 HIV-positive MSM, the use of HAART was associated with lower prevalence of AIN and a significantly lower prevalence of HPV. This association between the prevalence of AIN and the absence of HAART may contribute to the current debate on when to start HAART in HIV-infected individuals.

Human papillomavirus-associated diseases in HIV-infected men who have sex with men

Persistent human papillomavirus (HPV) infection is very frequent in HIV-positive men who have sex with men. This review summarizes recent data on papillomavirus-induced anal intraepithelial neoplasia and anal cancer in these patients. Moreover, data are provided on penile and oral HPV-associated diseases, for which only limited information is available in the literature. The incidence of anal intraepithelial neoplasia rises in HIV-positive men who have sex with men despite the introduction of highly active antiretroviral therapy. Increasing evidence indicates that high-grade lesions can progress to anal cancer over time. Anal cytology has been recommended as the primary screening tool for anal dysplasia in the at-risk population. Individuals with abnormal cytology should undergo high-resolution anoscopy to appropriately identify and treat dysplastic lesions. Anal cancer has become one of the most common non-AIDS-defining tumors in HIV-infected individuals. In the era of highly active antiretroviral therapy, the outcome of combined chemoradiotherapy in HIV-positive individuals with anal cancer is similar to that in HIV-negative persons. Penile and oral HPV-associated diseases seem to be more frequent in HIV-positive men than reported for HIV-negative heterosexual men. Diagnostic and therapeutic guidelines should be implemented for at-risk populations for anal dysplasia/anal cancer, such as HIV-positive men who have sex with men. More study is required to get better insights into the natural history of penile and oral HPV-associated benign and malignant lesions.

Human papillomavirus-related tumors in HIV

Human papillomavirus-related anogenital cancers are theoretically preventable. Many HIV-infected women do not undergo routine cervical cytology screening, however, and there are currently no routine anal cytology screening programs. This review focuses on recent developments that may impact on the future incidence of these cancers: the effect of highly active antiretroviral therapy and the imminent approval of vaccines to prevent initial human papillomavirus infection. Highly active antiretroviral therapy has limited benefit to reduce the incidence of cervical intraepithelial neoplasia 3 and no benefit to reduce the incidence of anal intraepithelial neoplasia 3. Consistent with these findings, there has been no reduction in the incidence of cervical and anal cancer since the introduction of highly active antiretroviral therapy. More encouraging is the development of highly effective preventive human papillomavirus vaccines that are projected to reduce the incidence of cervical cancer by up to 70% among vaccinated women. HIV-positive men and women remain at risk for human papillomavirus-associated cancers, even in the highly active antiretroviral therapy era. Conversely, the incidence of anogenital cancers may decline in the future among HIV-positive individuals if they received the human papillomavirus vaccine before they acquired HIV infection, and studies should be done to assess the safety and efficacy of the vaccines in individuals already infected with HIV.

Human immunodeficiency virus infection and genital warts as risk factors for anal intraepithelial neoplasia in homosexual men.

The incidence of anal intraepithelial neoplasia (AIN) was studied in a group of 210 homosexual and bisexual men. The presence of genital warts and human immunodeficiency virus (HIV) infection was assessed as risk factors for the development of AIN. In all, 74 (35 per cent) of the group had histological evidence of AIN. The relative risk of being positive for HIV on AIN (relative to being negative for HIV) was 1.58 (95 per cent confidence interval (c.i.) 1.01-2.48). The relative risk of anal warts on AIN (relative to absence of anal warts) was 4.70 (95 per cent c.i. 1.81-12.20). Logistic regression analysis showed no significant interactive effect between HIV and anal warts on the risk of AIN. It is concluded from the results of a Mantel-Haenzel analysis that the presence of anal warts and HIV infection are independent risk factors for the development of AIN in homosexual and bisexual men.

Screening and therapy of anal intraepithelial neoplasia (AIN) and anal carcinoma in patients with HIV-infection

Anal intraepithelial neoplasia (AIN) is a potential precursor of invasive anal carcinoma. Introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV infection substantially reduced the incidence of some diseases associated with opportunistic viral infections. However, the incidence of AIN is reported to increase and HAART seems to have only little impact on the regression or progression of AIN. Paradoxically, improvement of survival in the HAART era results in an increased risk of anal cancer. The incidence of anal carcinoma amongst homosexual men is substantially higher compared to the normal population (35/100.000). This incidence is similar to the incidence of cervical cancer before screening for CIN with cervical cytology. Recent data suggest that the incidence of AIN and anal cancer is even higher among HIV-infected individuals. Both cancer entities share biologic similarities, including the association with human papillomavirus infection (HPV). Screening for CIN with cervical cytology and early treatment has resulted in a significant decline in the incidence of cervical carcinoma. Like cervical cancer, anal carcinoma may be preventable through identification and treatment of its precursors. Future efforts should focus on a screening protocol, training of clinicians in the diagnosis and treatment of AIN and anal carcinoma, and novel approaches to treatment of these lesions. This screening protocol could help to reduce anal cancer in HIV-infection as well as save limited resources in health care system.