Anal Cancer- Can it be prevented? Lecture in Houston this Thurs June 21Nelson Vergel
Rates of anal cancer among gay and bisexual men are 35 times greater than the general population
HIV+ men and women are 80 times more likely to have anal cancer.
THE GOOD NEWS IS THAT ANAL CANCER IS POTENTIALLY PREVENTABLE AND HIGHLY CURABLE.
Come to hear Houston’s Dr. Eric Haas speak about ways to detect and treat it early.
Location: United Way at 50 Waugh Drive, Houston
Map: Map of 50 Waugh Dr Houston, TX by MapQuest
When: This Thursday, June 21, 6:30 p.m. Light dinner provided. Limited seating. RSVP to 713-520-5288
This is the first seminar of its kind on this topic in Houston which is not talked about in the community
ABOUT THE SPEAKER:
Dr. Eric Haas earned his medical degree from the University of Texas Medical School at Houston, did his General Surgery Internship at the M.D. Anderson Cancer Center and completed his General Surgery Residency at St Joseph Hospital. He is board certified by both the American Board of Surgery and by the American Board of Colon and Rectal Surgery. He is the Director of Aparoscopic Colon and Rectal Surgery and has received the 2005 Chief Resident Award for most outstanding Academic Faculty for the Methodist/St. Joseph Hospital General Surgery Residency Program. In addition, Dr. Haas serves as faculty surgeon at The Methodist Hospital, St Luke’s Hospital , and Memorial Hermann Hospital. More info on (http://www.houstoncolon.com)
More on the subject:
Bay Area doctors promote Pap tests for gay men to combat cancer
(04-21) 13:18 PDT San Francisco (AP) —
Some Bay Area doctors are promoting Pap tests for gay men to reduce rising rates of anal cancer.
U.S. cases of anal cancer have risen 37 percent in the last 10 years, compared to a 1 percent increase in overall cancer cases. Part of the increase is believed to be because of better reporting.
Anal Pap smears would help doctors detect precancerous lesions before they turn malignant, said Dr. Joel Palefsky, director of the Anal Neoplasia Clinic at the University of California, San Francisco.
“We haven’t proven it yet, but we believe that we are likely to be preventing anal cancer,” said Palefsky, who is preparing a report on anal cancer prevention.
Other doctors say there is disagreement over whether the tests are necessary or effective. The test should be left to the doctor’s and patient’s discretion, said Dr. Michael Horberg, director of HIV-AIDS for Kaiser Permanente and an HIV specialist at Kaiser Santa Clara Medical Center.
The American Cancer Society said there were about 4,660 cases of anal cancer in the United States last year, resulting in 660 deaths. Anal cancer accounts for less than 1 percent of cancer cases and is readily treatable if detected.
Overall, more women than man get anal cancer. But the disease is disproportionately high among gay men and people who are HIV-positive or have other immune-suppressive conditions.
Studies have found rates of anal cancer as high as 35 cases for every 100,000 gay men, similar to rates for cervical cancer before women began routinely getting Pap tests 60 years ago. Cervical cancer rates have dropped 70 percent since then. Both cancers are caused by the same sexually transmitted virus.
“Anal cancer is a silent issue that’s been building for at least 10 years,” said Jason Riggs, a spokesman for the Stop AIDS Project. “And it’s sad because it’s incredibly preventable.”
Information from: San Francisco Chronicle,
Cancer Rates in HIV Positive People in the HAART Era
By Liz Highleyman
Past research has yielded conflicting data on rates of cancer in HIV positive individuals since the advent of HAART. While effective therapy has reduced in incidence of some opportunistic malignancies, other types of cancer may be more common now that people with HIV are living longer.
Review of Cancer in People with HIVIn the May 2007 issue of Oncology Reports, G. Barbaro and G. Barbarini of University La Sapienza in Rome presented a review of cancer studies in the HAART era.The authors noted that the majority of cancers affecting HIV positive individuals are AIDS-defining malignancies including Kaposi’s sarcoma (KS), non-Hodgkin’s lymphoma (NHL), and invasive cervical cancer (ICC). However, they added, other types of cancer — such as Hodgkin’s disease, anal cancer, lung cancer, and testicular tumors — appear to be more common among HIV positive people compared with the general population. While not classified as AIDS-defining, these cancers have been referred to as AIDS-associated malignancies. Some experts believe invasive anal cancer, like ICC, should be considered AIDS-defining.The mechanisms by which immune suppression could increase the risk for cancer are unclear, the authors wrote, except for KS and most subtypes of NHL, which are strictly associated with low CD4 counts. Although it remains unclear whether HIV acts directly as an oncogenic (cancer-causing) agent, the virus may contribute to the development of malignancies through several mechanisms, including impaired immune surveillance and/or an imbalance between cell proliferation and differentiation. While a significant decrease in the incidence of KS has been observed with the widespread use of combination antiretroviral therapy, they continued, HAART has not had a significant impact on the incidence of NHL (particularly systemic NHL), Hodgkin’s disease, ICC, anal cancer, or other non-AIDS-defining malignancies. Barbaro and Barbarini concluded that regardless of whether these cancers are directly related to HIV-induced immunodeficiency, “treating cancer in HIV-infected patients remains a challenge because of drug interactions, compounded side effects, and the potential effect of chemotherapy on CD4 count and HIV-1 viral load.””A better knowledge of viral mechanisms of immune evasion and manipulation will provide the basis for a better management and treatment of the malignancies associated with chronic viral infections,” they added.Cancer Rates in CaliforniaCalifornia researchers presented results from a study of cancer rates among HIV positive people in the May 15th American Journal of Epidemiology. The investigators analyzed data from adults in the San Francisco AIDS surveillance registry and patients in the California Cancer Registry matched for age, sex, and race. Adjusted standardized incidence ratios (SIRs) were computed, and proportional hazards models evaluated the effect of HAART use on cancer incidence and survival time. Results
• Among 14,210 adults with AIDS diagnosed in 1990-2000, 482 non-AIDS-defining cancers were diagnosed. • Overall, the risk of developing non-AIDS-related cancers was somewhat higher among all HIV positive individuals during the HAART era (a 43% increased risk), but slightly lower for those who actually used HAART (21% reduced risk).• Compared with rates for the general population, significantly higher incidence rates were observed for:- anal cancer (SIR 13.4);- Hodgkin’s lymphoma (SIR 11.5);- liver cancer (SIR 3.6);- cancers of the mouth and throat (SIR 2.6);- respiratory tract cancers (SIR 2.6);- leukemia (SIR 2.4);- melanoma of the skin (SIR 2.4);- prostate cancer (SIR 1.7). • The risk of liver cancer was lower with HAART use (relative hazard [RH] 0.32). • The risk of anal cancer increased after 1995 (RH 2.9). • Respiratory tract cancers (RH 0.40) and Hodgkin’s lymphoma (RH 0.17) showed increased cancer survival times with HAART use.• Survival with anal cancer may have decreased slightly (RH 1.4).
ConclusionIn conclusion, the authors wrote, “The impact of HAART on non-AIDS-defining cancer incidence rates and survival is not uniform, and the mechanism(s) responsible for these differences should be investigated further.””We found that HAART use does not appear to substantially reduce the risk of non-AIDS cancers, and the impact of HAART on specific non-AIDS-defining cancer incidence rates and survival time is not uniform,” lead author Nancy Hessol told Reuters Health. “The underlying etiology for each cancer type contributes to this observed variation, along with changes in HIV and cancer treatments.”
Hessol recommended better cancer screening and prevention for people with HIV. For example, she said, “given the high rate of anal cancers in HIV-infected men who have sex with men, anal Pap testing should be encouraged for early detection and treatment of pre-cancerous and cancerous lesions.”
Department of Medicine, University of California, San Francisco, CA; AIDS Office, San Francisco Department of Public Health, San Francisco, CA; California Cancer Registry, Public Health Institute, Sacramento, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.
ReferencesG Barbaro and G Barbini. HIV infection and cancer in the era of highly active antiretroviral therapy (Review). Oncology Reports 17(5): 1121-1126. May 2007.NA Hessol, S Pipkin, S Schwarcz, and others. The Impact of Highly Active Antiretroviral Therapy on Non-AIDS-Defining Cancers among Adults with AIDS. American Journal of Epidemiology 165(10): 1143-1153. May 15, 2007.
Anal pre-cancer test for HIV-positive men
LOS ANGELES, March 22 (UPI) — A type of anal-canal Pap smear has been found to detect precancerous changes in the anal canals of HIV-positive men, a U.S. study found.The University of California at Los Angeles study found abnormal anal cytology — anal-canal Pap smear — was highly predictive of anal cell abnormalities that were subsequently confirmed by anal biopsy.The study, published in the International Journal of STD & AIDS, was based on data from 244 patients at the UCLA CARE clinic who had anal cytology screenings between February 2002 and December 2004.HIV-positive men who have sex with men are up to 90 times more likely than the general population to develop anal cancer, according to UCLA CARE clinic.The UCLA CARE Center is one of a few U.S. clinics offering anal dysplasia screening, a procedure that has not yet entered standard practice.“The prevalence, and predictive value, of abnormal anal cytology to diagnose anal dysplasia in a population of HIV-positive men who have sex with men”R D Cranston*, S D Hart- J A Gornbein , S L Hirschowitz-, G Cortina- and A A Moe§*Department of General Internal Medicine; -Department of Pathology; Department of Biomathematics;§ Department of Infectious Disease,University of California, Los Angeles, CA, USATo date, most of the information available on anal dysplasia is derived from a limited number of natural history studies. This current study reflects clinical practice in a HIV primary care setting and aims to (1) estimate the prevalence of anal cytologic abnormalities, (2) estimate the positive predictive value of anal cytology for any degree of dysplasia and for high-grade dysplasia.“…….screening for anal cytological abnormality, defining the abnormality pathologically by anal biopsy, and subsequently treating potentially premalignant lesion(s) has been proposed as a management strategy for the anal canal to prevent the progression of high-grade dysplasia to anal cancer….… detection of abnormal anal cytology is useful clinically in HIV-positive MSM to predict the presence of anal dysplasia. In this study, 96% of the samples were adequate for cytological interpretation. The majority of abnormal cytology samples showed lower grades of dysplasia while more than half of these abnormal cytology specimens had high-grade dysplasia on biopsy. Thus, any abnormality on anal cytology testing should prompt HRA follow-up to determine grade of dysplasia and allow consideration of treatment for high-grade disease.….anal cytology underestimated the degree of anal dysplasia… While only 6% of the cytology results indicated high-grade lesions or possible high0grade lesions, the researchers found, 52% of biopsy specimens were either grades 2 or 3 anal intraepithelial neoplasia……Despite the poor correlation of anal cytology with biopsy, empirically abnormal anal cytology identified subjects that were then referred for HRA and biopsy with over half of these subjects subsequently diagnosed with high-grade disease and referred for treatment….….Anal cytology grade showed poor correlation with the grade of dysplasia detected by paired HRA-directed anal biopsy. Ninety-two percent of the abnormal anal cytology was ASC-US or LSIL, however anal pathology reports showed high-grade dysplasia (anal intraepithelial neoplasia] [AIN] 2 or 3) in 52% of specimens, indicating that anal cytology underestimated the degree of anal dysplasia….Previous modalities used to treat high-grade dysplasia have included cold scalpel excision with electrofulguration that showed lower rates of treatment efficacy in an HIV-positive population.25 More recently, the use of infrared coagulation (IRC) to treat high-grade dysplasia has been associated with higher efficacy rates with reduced post procedure pain…”Summary: Due to the increasing incidence of anal cancer in HIV-positive men who have sex with men, and the potential to detect and treat high-grade anal dysplasia – the putative anal cancer precursor – we have introduced an anal cytology screening service. Patients with abnormal anal cytology have follow-up high-resolution anoscopy (HRA) with biopsy of lesions clinically suspicious for high-grade dysplasia. In total, 244 men were screened and 235 (96%) of the samples were adequate for cytological interpretation using the Bethesda 2001 system. One hundred and sixty-four (67%) men had abnormal anal cytology, and 93 of them had follow-up HRA and anal biopsy. The positive predictive value for any anal cytological abnormality to predict any degree of anal dysplasia was 95.772.1%, and for any anal cytological abnormality to predict high-grade anal dysplasia was 55.975.1%. Abnormal anal cytology was highly predicative of anal dysplasia on biopsy.INTRODUCTIONAnal cancer is a rare malignancy accounting for only 1.5% of all gastrointestinal tumours.1 However, in certain groups, the incidence of anal cancer is increased in comparison to the general population. Prior to the HIV pandemic, the incidence of anal cancer in men who have sex with men (MSM) who practice receptive analintercourse (RAI) was approximately 35 per 100,000,2 equivalent to the incidence rate of cervical cancer prior to the introduction of cervical cytology screening in developed countries. Currently, the incidence of anal cancer in HIV-positive MSM is estimated to be between 70 and 80 per 100,000 based on studies in both Europe and the USA.3,4The anal and cervical canal share a common embryological origin, are classified cytologically using the same 2001 Bethesda system, and both develop dysplasia in association with anogenital human papillomavirus (HPV) infection.5 HPV can be grouped phenotypically into high-risk and low-risk HPV related to its association with cervical cancer.6 High-risk HPV, most commonly HPV 16 or 18, is present in almost 100% of anal and cervical cancers,7,8 and is now considered essential for the development of cervical cancer in association with co-factors such as cigarette smoking.9The presence of either HPV or anal dysplasia, unlike other HIV-related infections or tumours, does not appear to be significantly influenced by the introduction of highly active antiretroviral therapy (HAART).10,11 Moreover, reports from San Diego and San Francisco Counties have shown that the incidence of anal cancer in these regions has increased from the pre- to the post-HAART era.12,13 While it is unlikely that HAART therapy per se increases the risk of anal dysplasia and anal cancer, this finding may be explained by the fact that individuals with HIV infection taking HAART are living longer and allowing the anal canal to have prolonged exposure to oncogenic HPV in the context of relative immunosuppression.14 In addition, there is in vitro evidence that HIV tat protein interacts with the HPV genome to increase oncoproteinexpression that leads to chromosomal dysregulation and the potential of malignant cellulartransformation.15,16Using the cervical paradigm, screening for anal cytological abnormality, defining the abnormality pathologically by anal biopsy, and subsequently treating potentially premalignant lesion(s) has been proposed as a management strategy for the anal canal to prevent the progression of high-grade dysplasia to anal cancer. Anal cytology screening has similar sensitivity to cervical cytology screening in HIV-positive MSM to detect the presence of dysplastic cells.17,18 Liquid-based cytology collection methods are increasingly being used for the cervix, and have the advantage that remnant liquid fixative may be tested for HPV, as occurs in the triage of cervical samples that show atypical squamous cells of undetermined significance (ASC-US). The liquid cytology method may additionally abrogate potential problems associated with hypocelluarity, air drying artefact and faecal contamination in anal samples.17,19 While no national or international guidelines exist for anal cytology screening, investigators from the largest natural history study at the University of California, San Francisco, have suggested the following screening algorithm in MSM:– Normal anal cytology is repeated in one year in an HIV-positive population and in two to three years in an HIV-negative population. — All abnormal anal cytology is referred for high-resolution anoscopy (HRA). At HRA a biopsy is taken of any lesion(s) suspicious for dysplasia based on standard colposcopic criteria.20 If no dysplasia is identified, the individual has routine anal cytology screening as above. Using this system, the aim of anal cytology testing is to detect either normal or abnormal results, as previous studies have shown that anal cytology grade is poorly predictive of anal dysplasia grade following HRA and biopsy, and should not be relied upon without histological confirmation.21 — Low-grade dysplasia on biopsy is followed up at six-monthly intervals with HRA due to the high rate of progression from low-grade to high-grade dysplasia.22 — High-grade dysplasia on biopsy is treated, or followed-up depending on the size of the lesion.To date, most of the information available on anal dysplasia is derived from a limited number of natural history studies. This current study reflects clinical practice in a HIV primary care setting and aims to (1) estimate the prevalence of anal cytologic abnormalities, (2) estimate the positive predictive value of anal cytology for any degree of dysplasia and for high-grade dysplasia.METHODSSubjectsAll subjects in this clinical study were MSM who attend the University of California Los Angeles (UCLA) Center for AIDS Research and Education (CARE) clinic. Anal cytology specimens were collected sequentially at the discretion of the treating clinician.Anal cytology collectionPrimary care physicians received anal cytology collection training. The cytology specimens were taken using a water-moistened Dacront swab and ThinPrept collection method with the patient in the left lateral position. The Dacront swab was introduced two inches beyond the anal margin, and removed with lateral pressure and a spiral motion over 10 seconds. After removal, the swab was immediately immersed and agitated in ThinPrept solution to disgorge the cells. Anal cytology samples were read by a UCLA cytopathologist and reported as ASC-US, atypical squamous cells cannot rule out high-grade (ASC-H), lowgradesquamous intraepithelial lesions (LSIL), or highgrade squamous intraepithelial lesions (HSIL) using Bethesda 2001 terminology.5High-resolution anoscopyOne practitioner performed all HRA exams. All patients with abnormal anal cytology were referred for further evaluation using HRA. This procedure uses a high-resolution anoscope (colposcope) set at 16 magnification to examine the peri-anal area and anal canal after the application of 3% acetic acid.23 The acetic acid causes acetowhitening of dysplastic anal epithelium similar to the effect on cervical squamous epithelium. Cervical colposcopic features of high-grade dysplasia such as coarse punctuation and mosiacism have been shown to similarly indicate high-grade disease in the anal canal.20 Abnormal acetowhite epithelium was biopsied using disposable Trilobites (ESCO medical Instruments, Stony Brook, NY, USA) endoscopic forceps with a 2.3mm non-serrated cup. The biopsy specimens were immediately fixed in 10% formalin. Haemostasis was achieved with Monsell’s solution prior to the end of the procedure.Biopsies were processed using standard paraffin processing and read following staining with haematoxylin and eosin.Statistical analysisBiopsy results are used as the gold standard in the statistical analysis. Since biopsies were performed only for patients with non-negative cytology, estimates of sensitivity, specificity or likelihood ratios based on sensitivity and specificity using this data are biased and uninformative. Negative predictive values (NPV) also cannot be computed since no negative patients were biopsied. The positive predictive value (PPV) is computed using those with AIN 1, 2 or 3 biopsy results as true positives and is also computed using only AIN 2 or 3 as true positive. The weighted kappa statistic is computed as a measure of agreement beyond chance between the ordered cytology versus biopsy results and the Spearman rank correlation (rs) is computed as a measure of association between the ordinal cytology versus biopsy results. Computations were carried out using StatXact version 5.0 (Cytel Software Inc., Cambridge, MA, USA). Results are reported as estimate7standard error.RESULTSA total of 244 patients had anal cytology screening between February 2002 and December 2004. The average age of patients was 44.1 years (range of 22-71 years), and ethnic breakdown was African American 8% (19), Asian 4% (9), Caucasian 72% (176), and Latino 16% (39) and Others 0% (1) – consistent with the general clinic population. The mean CD4 count at screening cytology was 457 cells per mm3 (range 1-1408 cells/mm3).Twenty-nine percent (71) of patients had normal anal cytology, 67% (164) had abnormal anal cytology and 4% (9) of samples were unsatisfactory for interpretation due to hypocellularity (5), bacterial excess (2) and a predominance of anucleated squames (2). Abnormal cytology was reported as — ASC-US in 48% (78) (atypical squamous cells of undetermined significance)– ASC-H in 3% (5) (atypical squamous cells-high grade)– LSIL in 46% (76) ( low-grade squamous intraepithelial lesions)– HSIL in 3% (5) (high-grade squamous intraepithelial lesions)Of the 166 patients with abnormal anal cytology, 93 had follow-up HRA and anal biopsy (Table 2). Patients who did not have HRA had either elected not to have the procedure or have yet to make an appointment.Anal cytology grade showed poor correlation with the grade of dysplasia detected by paired HRA-directed anal biopsy. Ninety-two percent of the abnormal anal cytology was ASC-US or LSIL, however anal pathology reports showed high-grade dysplasia (anal intraepithelial neoplasia] [AIN] 2 or 3) in 52% of specimens, indicating that anal cytology underestimated the degree of anal dysplasia. The weighted kappa statistic is 0.0370.06 (P1/40.6337) and the Spearman correlation is rs1/40.05670.106 (P1/40.5956),confirming poor agreement and correlation within the group of positive tests.The PPV for any grade of anal cytological abnormality to predict any grade of anal dysplasia (AIN 1, 2 or 3) on biopsy was 95.772.1%. The PPV for any grade of anal dysplasia to predict high-grade anal dysplasia (AIN 2 or 3) on biopsy was 55.975.1%.No significant adverse events such as infection, haemorrhage or pain uncontrolled with simple analgesia were reported in the study.DISCUSSIONThe clinicians in this study received one short training session on how to take an adequate anal cytology specimen and were able to collect adequate anal cytology samples in the majority of cases similar to a previous study.24 However, compared with previous studies, the grade of cytology was predominantly ASC-US and LSIL with fewer samples showing HSIL.21 This may have been due to the technique employed by the sampling clinicians or may reflect cytopathological reporting. Assuming this result is more likely to reflect anal cytological sampling technique, repeating sampling technique instruction may have resulted in specimens that more closely reflect the anal cellular environment.This study corroborates the poor correlation between the cytological grade of anal dysplasia and the histopathological examination of matched anal biopsy collected during HRA.21 As no patients with normal anal cytology were referred for HRA, sensitivity, specificity or NPV could not be reported for this population. However, given the high- PPVs of abnormal anal cytology to detect any grade of anal dysplasia, clinicians may be confident that an abnormal cytology result is likely to indicate the presence of some grade of anal dysplasia.Despite the poor correlation of anal cytology with biopsy, empirically abnormal anal cytology identified subjects that were then referred for HRA and biopsy with over half of these subjects subsequently diagnosed with high-grade disease and referred for treatment. Previous modalities used to treat high-grade dysplasia have included cold scalpel excision with electrofulguration that showed lower rates of treatment efficacy in an HIV-positive population.25 More recently, the use of infrared coagulation (IRC) to treat high-grade dysplasia has been associated with higher efficacy rates with reduced post procedure pain.26 This device is used in an outpatient setting and delivers infra red light in aliquots of 0.5-3 second intervals (1.5 seconds for anal dysplasia) to previously anesthetized anal epithelium producing a focal shallow burn that reflects the time setting in mm, i.e. setting the IRC at 1.5 seconds will deliver a burn depth of 1.5mm26,27 Early clinical reports indicate efficacy (with follow-up biopsies showing normal or low-grade dysplasia) of 72% at six months.27If referral for HRA is not available, patients with abnormal anal cytology should be informed about the risk of progression to anal cancer particularly with high-grade cytology results. Additionally, they should be made aware of common presenting symptoms of anal cancer such as pain, bleeding and the presence of a mass that would allow early investigation and referral for treatment.The result of this study is likely to be reflective of other HIV primary care settings in the USA that have a predominance of Caucasian MSM over the age of 40 years. Thus, these clinics may also have a high burden of undiagnosed anal dysplasia.In conclusion, detection of abnormal anal cytology is useful clinically in HIV-positive MSM to predict the presence of anal dysplasia. In this study, 96% of the samples were adequate for cytological interpretation. The majority of abnormal cytology samples showed lower grades of dysplasia while more than half of these abnormal cytology specimens had high-grade dysplasia on biopsy. Thus, any abnormality on anal cytology testing should prompt HRA follow-up to determine grade of dysplasia and allow consideration of treatment for high-grade disease.