Incidence Of Invasive Anal Cancer Research Articles

Cumulative incidence of anal cancer since HIV or AIDS diagnosis in the United States.

Treatment of screen-detected anal high-grade squamous intraepithelial lesions has been shown to effectively reduce the incidence of invasive anal cancer in people with HIV. We provide population-based estimates of cumulative incidence of anal cancer by risk group and age at HIV or AIDS diagnosis. The 0- to 10-year cumulative incidence of anal cancer for men who have sex with men and are younger than 30years of age at HIV diagnosis was 0.17% (95% confidence interval [CI] = 0.13% to 0.20%) compared with 0.04% (95% CI = 0.02% to 0.06%) in other men and 0.03% (95% CI = 0.01% to 0.04%) in women. For men who have sex with men and have a diagnosis of AIDS and are younger than 30years of age, the 0- to 10-year cumulative incidence was 0.35% (95% CI = 0.28% to 0.41%). Among people with HIV, men who have sex with men are at the greatest risk of anal cancer, and those with a diagnosis of AIDS had higher risk than those without AIDS. These estimates may inform recommendations for priority populations that could benefit most from anal cancer screening and treatment.

Significance of the Cytological Signs of Human Papillomavirus Infection in Anal Pap Smears of Human Immunodeficiency Virus-Infected Japanese Men Who Have Sex with Men

Purpose:The incidence of invasive anal cancer (IAC) has been increasing among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). Although cytological diagnosis is the modality of choice for screening cases of IAC, it is associated with lower sensitivity and specificity. Therefore, the present study aimed to evaluate new cytological signs of human papillomavirus (HPV) infection that may contribute to improving anal cytology.Methods:Anal cytology and HPV testing were performed using SurePath liquid-based cytology on samples obtained from 37 HIV-positive Japanese MSM. Subsequently, a histological biopsy based on high-resolution anoscopy was performed in MSM with abnormal cytological findings indicative of atypical squamous cells of undetermined significance (ASC-US) +. Also, anal Papanicolaou (Pap) smears were performed to determine cellularity, presence of dysplastic squamous cells, and other cytological signs of HPV infection.Results:Of the 37 MSM who underwent anal cytology, six tested negative for intraepithelial lesion or malignancy, three cases exhibited ASC-US, 17 exhibited low-grade squamous intraepithelial lesion (LSIL), nine exhibited high-grade squamous intraepithelial lesion (HSIL), and two remained undiagnosed. The anal Pap smears of 28 (96.6%) of the 29 MSM with abnormal cytological findings of ASC-US+ exhibited anal intraepithelial neoplasia (AIN), as revealed by histological biopsy. The median value (minimum–maximum) of the cellularity of anal Pap smears was 12 (0–70.5) nsc/hpf. In 26 MSM with LSIL and HSIL, the median dysplastic squamous cells count was 14 (2–152) dsc/smear and the cytological sign of HPV infection was 11 (2–71) hpv/smear. Of all anal Pap smears that revealed ASC-US+, 96.6% exhibited cytological signs of HPV infection. Compression-positive binucleated cells were the most prevalent among all cytological signs of HPV infection.Conclusion:For anal cytology, instead of considering a small number of dysplastic squamous cells, screening based on cytological signs of HPV infection may be beneficial for improving the diagnosis of AIN.

Anal cancer and intraepithelial neoplasia screening: A review.

This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations.

Five-year cumulative incidence of invasive anal cancer among HIV-infected patients according to baseline anal cytology results: an inception cohort analysis.

The aim of the study was to estimate the cumulative incidence of, and rates of progression to, invasive anal cancer (IAC) according to baseline anal cytology screening category in an unselected HIV clinical care cohort in the antiretroviral era. A retrospective cohort analysis of HIV-infected patients under care at the University of California at San Diego Owen Clinic was carried out. Patients were eligible for this analysis if they had at least two anal cytohistological results available for longitudinal analysis. Kaplan-Meier analysis was used to estimate the cumulative incidence of IAC over time according to baseline cytology category [less than high-grade intraepithelial lesion (HSIL) versus HSIL]. Cox regression analysis was used to adjust for the following covariates: antiretroviral use, level of HIV viraemia, smoking status and infrared photocoagulation (IRC) ablation therapy. Between 2000 and 2012, we followed 2804 HIV-infected patients for a median of 4 years under a clinic protocol requiring baseline anal cytology screening. Incident IAC was diagnosed in 23 patients. Patients with a baseline HSIL anal cytology had an estimated 5-year probability of progression to IAC of 1.7% and an estimated annual progression risk of 1 in 263. None of the examined covariates was significantly associated with IAC incidence when examined in separate unadjusted Cox models. HIV-infected patients with a baseline HSIL anal cytology had a 5-year cumulative incidence of IAC of 1.65%, with an upper 95% confidence bound of 4.5%. This population-based study provides quantitative risk estimates that may be used for counselling patients regarding management options for abnormal cytology results.

PALEFSKY ET AL. RESPOND

We agree with Katz et al. that “no prospective studies have demonstrated that performance of anal screening reduces the incidence of invasive anal cancer or of death due to cancer.” We also strongly agree that such a study is needed. However, we stand by our statement that anal cancer screening by anal Papanicolau test has potential benefits for gay and bisexual men. Anal cancer and its precursors are very similar to cervical cancer and its precursors.1 Based on the success of treating high-grade cervical intraepithelial neoplasia to reduce the risk of cervical cancer, we have good reason to believe that treating high-grade anal intraepithelial neoplasia (AIN) will achieve a similar reduction in anal cancer.1 Performing the study that we all agree is needed will take time, and it will be many years before we have the data necessary to implement the best evidence-based approaches to prevention of anal cancer. A key question is what to do now about high-grade AIN in men and women at risk for anal cancer until we have those data. Doing nothing about high-grade AIN is not a reasonable option given the unacceptably high rate of anal cancer in gay and bisexual men, as well as other groups known to be at high risk.2 There are precedents for treating other potentially precancerous lesions to prevent cancer without the benefit of the kind of randomized controlled trial evidence that we all agree is necessary. For example, ductal carcinoma in situ of the breast is routinely treated, sometimes with considerable morbidity, without prospective evidence that doing so reduces the mortality from breast cancer.3 We believe the best approach is to follow this example for now and work to collect the randomized controlled trial data as quickly as possible. Finally, while it is certainly true that anal cytology testing induces some anxiety and discomfort, most of our patients tolerate these procedures well. Screening for any kind of cancer is anxiety-producing, but anxiety for people with normal results typically falls quickly to pretest levels4 unless there is a testing error5 or other abnormal finding that requires follow-up. In our experience, treatment of high-grade AIN has a low complication rate, and our clinic retention rate is high. A diagnosis of anal cancer and its treatment can yield substantial physical and psychological distress that should not be underestimated.

WE NEED DATA ON ANAL SCREENING EFFECTIVENESS BEFORE FOCUSING ON INCREASING IT

We are concerned that the article by Reed et al. on gay and bisexual men's willingness to receive anal Papanicolaou (Pap) screening1 perpetuates the belief that such screening has been shown to be effective. This is not the case. No prospective studies have demonstrated that performance of anal screening reduces the incidence of invasive anal cancer or of death as a result of cancer.2 The authors’ statement that “it is promising that potential benefits of anal cancer screening for gay and bisexual men are comparable to observed benefits of cervical cancer screening for women”1(p1127) is tautological. Because the effectiveness of anal screening in gay and bisexual men is unknown, the two cited analyses3,4 assume that the effectiveness of treating lesions found using anal screening in men is similar to that of treating lesions found by using cervical screening in women. It is certainly possible that anal screening with Pap smears is an effective method of reducing invasive cancer. However, given the cost, the anxiety experienced by patients told that they have an abnormal anal Pap, and the discomfort caused by the treatment of lesions found through anal screening, the practice needs to be proven effective before we focus on encouraging more people to be tested.5 We should not advocate for spending scarce health dollars on medical procedures of no proven effectiveness when there are so many proven interventions that are not available to all who need them.

Marked increase in the incidence of invasive anal cancer among HIV-infected patients despite treatment with combination antiretroviral therapy

To describe the cases of anal cancer that appeared in the French Hospital Database on HIV between 1992 and 2004 and to study risk factors of anal cancer. We examined the incidence rates of anal cancer between 1992 and 2004 and the risk associated among 86,322 HIV-infected patients included in the French Hospital Database on HIV. We identified 132 cases of anal cancer, including 124 cases in men (94%), of whom 75% had sex with men. Median age at diagnosis was 42.8 years (interquartile range: 36.9-49.4). At diagnosis, 103 patients (78%) were receiving combination antiretroviral therapy for a median of 37.1 months (interquartile range: 4.5-59.8). Median survival after anal cancer diagnosis was 5 years. The respective overall incidence rates of anal cancer per 100,000 person-years between 1992 and March 1996, April 1996 to 1998 and between 1999 and 2004 were 11 (95% confidence interval, 4-17), 18 (95% confidence interval, 10-27) and 40 (95% confidence interval, 32-47). The risk of anal cancer was higher among men who have sex with men. After adjustment for age at inclusion in the study, as well as gender, the HIV transmission group, the nadir CD4 cell count and AIDS status, the incidence was higher in the years 1999-2004 than in between 1992 to March 1996 (hazard ratio, 2.5; 95% confidence interval, 1.2-5.3), with no change in the years 1999-2004. The incidence of anal cancer has increased among HIV-infected patients in France since 1996. Although an ascertainment bias cannot be excluded, data indicate that combination antiretroviral therapy does not prevent anal cancer in these patients. This supports the urgent need for developing anal cancer screening programs for HIV-infected men who have sex with men.

A retrospective review of anal squamous cell carcinoma in HIV positive and HIV negative patients

4153 Background: The incidence of invasive anal cancer is 120 times higher in the HIV infected patients than in the general population. The outcome of anal cancer in HIV infected patients has not been evaluated in prospective trials and the published literature is limited to small retrospective case series. The aim of this study is to describe the outcome, tolerability, event free survival, and overall survival in patients with squamous cell carcinoma of anal canal (SCCAC) with and without HIV infection treated at Karmanos Cancer Institute/Wayne State University from 1991 to 2005. Methods: We performed a retrospective chart review. Patients were identified using the SEER database. We collected data regarding HIV status, demographics (age, gender, race), stage at diagnosis, treatment, response to treatment, toxicity and survival. Results: Forty patients with SCCAC were identified, of which 13 were HIV positive and 27 were HIV negative. The HIV-positive and HIV-negative groups differed by mean age (44 vs. 55 years), male gender (100 vs. 37 percent), and African American race (92 vs. 59 percent). There were no differences in stage at diagnosis, type of chemotherapy received. HIV positive population received reduced chemotherapy (67 vs. 8 percent), and RT (22 vs. 7 percent) dosage. The major toxicities observed in HIV positive and negative patients were mucositis (23% vs. 29%), neutropenia (8% vs. 33%) and skin toxicity (46% vs. 55%) secondary to radiotherapy. Only 61 percent of HIV-positive patients were disease free vs. 60 percent of HIV-negative patients. Conclusions: We found that HIV positive patients received lower doses of chemo-radiotherapy. Patients with HIV tolerated the lower dose chemoradiotherapy and had a similar toxicity profile to the HIV negative patients. No major difference in the risk of recurrence between HIV positive and negative patients was observed. No significant financial relationships to disclose.

Increased Incidence of Squamous Cell Anal Cancer Among Men With AIDS in the Era of Highly Active Antiretroviral Therapy

We sought to determine if the introduction of highly active antiretroviral therapy (HAART) corresponded with changes in anal squamous cell cancer rates among men with AIDS. We linked cancer registry data from 1988-2000 and AIDS registry data from 1981-July/2003 for San Diego County. We defined 1991-1995 and 1996-2000 as the pre- and post-HAART periods, respectively. The annual incidence of invasive anal cancer increased from zero per 100,000 men with AIDS aged 25 to 64 years (95% confidence interval [CI], 0-226) in 1991 to 224 per 100,000 (95% CI, 102-425) in the year 2000. Pre-HAART, the average annual incidence of invasive anal cancer was 49 per 100,000 men with AIDS aged 25 to 64 years (95% CI, 16-114) versus 144 per 100,000 (95% CI, 93-212) post-HAART. The relative risk of invasive anal cancer among men with AIDS compared with men without known HIV/AIDS was 98 (95% CI, 36-264) pre-HAART and 352 (95% CI, 186-669) post-HAART. The increased incidence of anal cancer among men with AIDS resulted in an increase in the overall rate of anal cancer among men in San Diego County. The rising incidence of anal cancer among men with AIDS may be related to increased longevity with HAART and the consequent increased time at risk for the development of malignancy and/or the result of greater use of cytologic screening.

HIV-Associated Anal Cancer

Highly active antiretroviral therapy (HAART) has reduced the incidence and improved the survival of patients with Kaposi sarcoma and AIDS-related non-Hodgkin lymphoma. We wished to evaluate its effects on incidence and survival in HIV-associated anal cancer. We measured the incidence and survival of patients with invasive anal cancer from our prospective cohort of 8640 HIV-seropositive individuals. In our cohort of 8640 HIV-seropositive individuals, the incidence of invasive anal cancer (diagnosed in 26 patients) is 60 per 100,000 patient-years. This is 120 times higher than in the age- and gender-matched general population. The incidence of invasive anal cancer in the HIV cohort was 35 (95% confidence interval CI: 15-72) per 100,000 patient-years of follow-up in the pre-HAARTera (1984-1995) and 92 (95% CI: 52-149) per 100,000 patient-years of follow-up in the post-HAARTera (1996-2003) (P > 0.05). These figures are significantly higher than those for the general population (P < 0.001 for both) and give a relative risk of 67 and 176 in the pre- and post-HAART eras, respectively, compared with the general population. The 5-year overall survival is 47% (95% CI: 24%-70%), and the 5-year disease-free survival is 66% (95% CI: 45%-87%). There is no difference in overall survival between the pre- and post-HAART eras (log rank P = 0.19). Unlike other HIV-associated cancers, there has been no significant change in the incidence, clinical features, or overall survival since the introduction of HAART.

Natural History and Clinical Management of Anal Human Papillomavirus Disease in Men and Women Infected with Human Immunodeficiency Virus

Before the introduction of highly active antiretroviral therapy (HAART), several studies demonstrated a high prevalence of human papillomavirus (HPV) infection and associated anal intraepithelial neoplasia (AIN) in men who have sex with men, particularly in human immunodeficiency virus (HIV)-infected men with low CD4+ cell counts. Similarly high levels of anal HPV infection and AIN have been found in HIV-positive women. HIV-positive men and women are at an increased risk of developing anal cancer compared with the general population. Data suggest that there has been no reduction in the incidence of AIN after the introduction of HAART. Screening efforts have the potential to decrease the incidence of invasive anal cancer, and cost-effectiveness analyses have demonstrated the utility of anal cancer screening in select populations. Treatment for AIN remains challenging, but AIN is easier to treat when the lesions are small, and it is likely that a screening program would identify affected individuals at an earlier stage of disease.

Human papillomavirus-associated malignancies in HIV-positive men and women

Human papillomavirus (HPV) infections of the anogenital tract and HPV-associated anogenital neoplasia are commonly found in HIV-positive men and women. Although there is little evidence suggesting that the incidence of invasive cervical cancer is increased in HIV-positive women, the incidence of invasive anal cancer may be increased in HIV-positive men. Among HIV-positive women, cervical intraepithelial neoplasia progresses more rapidly and recurs more often after primary therapy than in HIV-negative women. HPV infection and HPV-associated disease are often multifocal in HIV-positive women, and they may be found in both the vulva and the anus. Cervical cytology appears to be adequate as a screening tool for cervical intraepithelial neoplasia in HIV-positive women, but the high recurrence rate and multifocal nature of this disease reinforces the need for careful evaluation and follow-up of the entire anogenital tract in these women.

Human papillomavirus-associated anogenital neoplasia and other solid tumors in human immunodeficiency virus-infected individuals.

The incidence and variety of solid tumors reported among human immunodeficiency virus (HIV)-infected individuals are increasing. Among the most common of these tumors are anogenital malignant and premalignant tumors associated with human papillomavirus infection. Cervical intraepithelial neoplasia is one such human papillomavirus-associated lesion and appears to be more common among women with HIV infection than HIV-negative women. Cervical intraepithelial neoplasia also appears to progress more rapidly among HIV-positive women, and these women are at high risk for progression to invasive cervical cancer in the absence of rigorous screening, treatment, and follow-up. Likewise, HIV-positive men with a history of receptive anal intercourse have a high prevalence of anal intraepithelial neoplasia and a rapidly increasing incidence of invasive anal cancer. The approach to the prevention of anal cancer is similar to that of cervical cancer, although experience with diagnostic and treatment measures is still limited for anal disease. As individuals with advanced immunosuppression live longer due to improvements in the medical therapy for HIV infection, it is expected that the incidence of human papillomavirus-associated neoplasia, as well as that of other tumors, will continue to increase.