Reliability and between-group stability of a health-related quality of life symptom index for persons with anal high-grade squamous intraepithelial lesions: an AIDS Malignancy Consortium Study (AMC-A03).

PURPOSE: The Anal Cancer HSIL Outcomes Research (ANCHOR) trial aims to determine whether treating precancerous anal high-grade squamous intraepithelial lesions (HSIL), versus active surveillance, is effective in reducing anal cancer incidence in HIV-infected individuals. We evaluated the reliability (i.e., internal consistency, test-retest) and between-group stability of a 25-item ANCHOR Health-Related Symptom Index (A-HRSI). METHODS: ANCHOR participants at least 1-month post-randomization to treatment or active surveillance completed the A-HRSI via telephone. Participants were contacted 7-10 days later to complete the A-HRSI and a participant global impression of change (PGIC) item. RESULTS: Participants (n = 100) were enrolled (mean age = 51.4, 79% cisgender-male, 73% African American, 9% Hispanic) from five ANCHOR sites. Cronbach's α was good for the physical symptoms (0.82) domain and fair for the physical impacts (0.79) and psychological symptoms (0.73) domains. Intraclass correlation coefficients were good for each of respective domains (i.e., 0.80, 0.85, and 0.82). There were no significant differences in PGIC between the treatment (n = 56) and active surveillance (n = 44) groups (F(1,98) = 2.03, p = 0.16). CONCLUSIONS: The A-HRSI is able to reliably assess participant-reported symptoms and impacts of anal HSIL across a 7-10 days of timeframe. Future work will involve the establishment of construct and discriminant validity prior to inclusion in the full ANCHOR trial.

Progression of anal high-grade squamous intraepithelial lesions to invasive anal cancer among HIV-infected men who have sex with men.

The incidence of anal cancer is elevated in human immunodeficiency virus (HIV)-infected men-who-have-sex-with-men (MSM) compared to the general population. Anal high-grade squamous intraepithelial lesions (HSIL) are common in HIV-infected MSM and the presumed precursors to anal squamous cell cancer; however, direct progression of HSIL to anal cancer has not been previously demonstrated. The medical records were reviewed of 138 HIV-infected MSM followed up at the University of California, San Francisco, who developed anal canal or perianal squamous cancer between 1997 and 2011. Men were followed up regularly with digital anorectal examination (DARE), high-resolution anoscopy (HRA) and HRA-guided biopsy. Although treatment for HSIL and follow-up were recommended, not all were treated and some were lost to follow-up. Prevalent cancer was found in 66 men. Seventy-two HIV-infected MSM developed anal cancer while under observation. In 27 men, anal cancer developed at a previously biopsied site of HSIL. An additional 45 men were not analyzed in this analysis due to inadequate documentation of HSIL in relation to cancer location. Of the 27 men with documented progression to cancer at the site of biopsy-proven HSIL, 20 men progressed from prevalent HSIL identified when first examined and seven men from incident HSIL. Prevalent HSIL progressed to cancer over an average of 57 months compared to 64 months for incident HSIL. Most men were asymptomatic, and cancers were detected by DARE. Anal HSIL has clear potential to progress to anal cancer in HIV-infected MSM. Early diagnosis is facilitated by careful follow-up. Carefully controlled studies evaluating efficacy of screening for and treatment of HSIL to prevent anal cancer are needed.

Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)-infected men are at increased risk for anal cancer. Human papillomavirus (HPV) vaccination may prevent anal cancer caused by vaccine types. METHODS: AIDS Malignancy Consortium Protocol 052 is a single-arm, open-label, multicenter clinical trial to assess the safety and immunogenicity of the quadrivalent HPV (types 6, 11, 16, and 18) vaccine in HIV-1-infected men. Men with high-grade anal intraepithelial neoplasia or anal cancer by history or by screening cytology or histology were excluded. Men received 0.5 mL intramuscularly at entry, week 8, and week 24. The primary end points were seroconversion to vaccine types at week 28, in men who were seronegative and without anal infection with the relevant HPV type at entry, and grade 3 or higher adverse events related to vaccination. RESULTS: There were no grade 3 or greater adverse events attributable to vaccination among the 109 men who received at least 1 vaccine dose. Seroconversion was observed for all 4 types: type 6 (59 [98%] of 60), type 11 (67 [99%] of 68), type 16 (62 [100%] of 62), and type 18 (74 [95%] of 78). No adverse effects on CD4 counts and plasma HIV-1 RNA levels were observed. CONCLUSIONS: The quadrivalent HPV vaccine appears safe and highly immunogenic in HIV-1-infected men. Efficacy studies in HIV-1-infected men are warranted. Clinical trials registration. NCT 00513526.

Performance characteristics of anal cytology and human papillomavirus testing in patients with high-resolution anoscopy-guided biopsy of high-grade anal intraepithelial neoplasia.

PURPOSE: High-resolution anoscopy is colposcopy of the anus after applying 3 percent acetic acid. High-resolution anoscopy with biopsy was used as the standard for detecting high-grade anal neoplasia and was compared to detection of high-grade anal neoplasia by anal cytology, human papillomavirus testing, or the combination. METHODS: A total of 125 men who have sex with men (MSM) were enrolled from a group of MSM identified by random digit dialing: HIV-negative = 85, HIV-positive = 35, and unknown status = 5. A specimen was taken for anal cytology and human papillomavirus testing, followed by high-resolution anoscopy with biopsy of any lesions. RESULTS: Ninety-one percent of HIV-positive and 57 percent of HIV-negative MSM had anal human papillomavirus infection. In HIV-positive men the sensitivity of abnormal cytology to detect high-grade anal neoplasia was 87 percent, and in HIV-negative MSM it was 55 percent. Among HIV-negative men, 9 of 20 cases of high-grade anal neoplasia would have been missed because cytology was negative, but the addition of human papillomavirus positivity increased sensitivity for the combination to 90 percent. CONCLUSIONS: Sensitivity and specificity of anal cytology and human papillomavirus testing are different in HIV-positive and HIV-negative MSM for detecting high-grade anal neoplasia when patients have high-resolution anoscopy-guided biopsy of lesions. The optimum use of human papillomavirus testing has yet to be defined. High-resolution anoscopy is an effective tool for diagnosing high-grade anal neoplasia.

Comparison of patient- and clinician-collected anal cytology samples to screen for human papillomavirus-associated anal intraepithelial neoplasia in men who have sex with men.

BACKGROUND: Human papillomavirus (HPV)-associated anal cancer is increasing in prevalence and is more common among men who have sex with men and HIV-positive individuals than cervical cancer is among women in the United States. Cytology screening can detect the anal cancer precursor, anal intraepithelial neoplasia (AIN). Little is known about self-collected samples for AIN screening, and few community-based AIN estimates exist. OBJECTIVE: To compare the sensitivity of self-collected versus clinician-collected anal cytology specimens to detect biopsy-confirmed AIN and the prevalence estimate of AIN in a community sample. DESIGN: Cross-sectional study. Participants were mailed anal cytology self-collection kits with instructions. Clinicians repeated anal cytology and performed high-resolution anoscopy with biopsies as the diagnostic reference standard. SETTING: San Francisco, California. PATIENTS: Community-based sample of men who have sex with men. MEASUREMENTS: Prevalence of anal HPV and AIN. Sensitivity and specificity of self-collected and clinician-collected anal cytology specimens to diagnose AIN were calculated. RESULTS: Biopsy-proven AIN was diagnosed in 57% of HIV-positive and 35% of HIV-negative participants (P = 0.04), and 80% provided adequate self-collected specimens for interpretation. The sensitivity of cytology to detect AIN in HIV-positive men was 75% (95% CI, 51% to 93%) when self-collected and 90% (CI, 68% to 99%) when clinician-collected; respective values in HIV-negative men were 48% (CI, 26% to 70%) and 62% (CI, 38% to 82%). The specificity of cytology to detect AIN in HIV-positive men was 50% (CI, 22% to 78%) when self-collected and 64% (CI, 36% to 86%) when clinician-collected; respective values in HIV-negative men were 86% (CI, 71% to 94%) and 85% (CI, 72% to 93%). LIMITATIONS: The study sample was from a narrowly defined geographical area. Participants self-reported HIV status. CONCLUSION: In a community-based sample, a high proportion of HIV-positive and HIV-negative men who have sex with men have AIN. The sensitivity of cytology to detect AIN is higher for clinician-collected versus self-collected specimens and for HIV-positive versus HIV-negative men. The specificity of cytology to detect AIN is higher in HIV-negative versus HIV-positive men. However, the probability of AIN in a patient with a negative cytology result may not be low enough (23% for HIV-negative men and 45% for HIV-positive men with a patient-collected specimen) for clinicians to be comfortable recommending no anoscopy for those with a negative cytology result if done as a one-time test. These data raise the question of whether the optimal population screening strategy is cytology screening with anoscopy only for those who test positive or whether anoscopy should be recommended for everyone in these risk groups. Given limited resources and the limited number of clinicians trained in anoscopy, cytology screening may be the best current approach to identifying disease in the at-risk population.

High-resolution anoscopy targeted surgical destruction of anal high-grade squamous intraepithelial lesions: a ten-year experience.

PURPOSE: This study was designed to determine whether high-resolution anoscopy and targeted surgical destruction of anal high-grade squamous intraepithelial lesions is effective in controlling high-grade squamous intraepithelial lesions while preserving normal tissues. METHODS: Retrospective review of 246 patients with high-grade squamous intraepithelial lesions treated with high-resolution anoscopy-targeted surgical destruction from 1996 to 2006, with at least one follow-up at a minimum two months with physical examination, high-resolution anoscopy, cytology, and biopsy when indicated. RESULTS: Lesions were extensive in 197 patients (81 percent); 207 (84 percent) were men, and 194 (79 percent) were immunocompromised (HIV or other). Persistent disease occurred in 46 patients (18.7 percent), requiring planned staged therapy; 10 required surgery. Recurrent high-grade squamous intraepithelial lesions occurred in 114 patients (57 percent) at an average 19 (range, 3-92) months; 26 of these required surgery. All other patients were retreated in-office with high-resolution anoscopy-directed therapies. Complications were seen in nine patients (4 percent). Despite treatment, three patients progressed to invasive cancer (1.2 percent). At their last visit, 192 patients (78 percent) had no evidence of high-grade squamous intraepithelial lesions. CONCLUSIONS: High-resolution anoscopy-targeted destruction combined with office-based surveillance and therapy is effective in controlling high-grade squamous intraepithelial lesions and is superior to reports of expectant management or traditional mapping procedures.

High resolution anoscopy in the planned staged treatment of anal squamous intraepithelial lesions in HIV-negative patients.

Anal dysplasia (low-grade squamous intraepithelial lesions, LSIL; high-grade squamous intraepithelial lesions, HSIL) is a challenging disease for the surgeon. We reviewed 42 patients that underwent high-resolution anoscopy (HRA)-targeted surgical therapy of anal dysplasia in the past 10 years. Patients were followed up in the Anal Neoplasia Clinic with physical examination, cytology, HRA, and biopsy if indicated. Patients with disease amenable to local therapy were treated with office-based HRA-directed therapies. There were 30 men (mean age 39 years, range 21-63) and 12 women (mean age 50 years, range 31-71) included in the study. HSIL was present in 33, with four undergoing planned staged treatment due to circumferential disease. HSIL recurred in 45%, and most were re-treated successfully in-office. Progression to HSIL was seen in one patient with LSIL and to squamous cell carcinoma in one patient with HSIL despite therapy. No patients with LSIL had dysplasia at last follow-up. Minor complications occurred in three patients. HRA-targeted surgical therapy coupled with surveillance and re-treatment with office-based therapies offered an effective method in controlling anal dysplasia in the immunocompetent patient. Morbidity is minimal, and our progression to cancer rate is low (2.4%).

A trial of SGN-00101 (HspE7) to treat high-grade anal intraepithelial neoplasia in HIV-positive individuals.

OBJECTIVES: To test a therapeutic vaccine consisting of a fusion of the human papillomavirus (HPV) 16 E7 protein and the Mycobacterium bovis heat shock protein 65 (SGN-00101) to treat high-grade anal intraepithelial neoplasia (HG-AIN) in HIV-positive individuals. DESIGN: A phase I/II trial with three cohorts of five participants each, sequentially assigned to receive 100, 500 or 1000 microg SGN-00101, injected three times subcutaneously in alternating thighs at 4-week intervals. Anal disease was assessed at baseline, 8, 12, 24 and 48 weeks and was classified as the more severe of anal cytology and anal biopsy. Anal HPV DNA was detected using L1 consensus primer-based PCR followed by type-specific probing and dot-blot hybridization (DBH). HPV16, 18 and 31 DNA copy numbers were measured using quantitative real-time PCR. SETTING: University-based research clinic. PARTICIPANTS: Thirteen HIV-positive men and two HIV-positive women with HG-AIN. RESULTS: There were no drug-related serious adverse events or significant changes in HIV viral load and CD4/CD8 ratio. At 48 weeks, two of five participants in both the 100 and 500 microg cohorts regressed to AIN 1 and one of five participants in the 1000 microg cohort regressed to atypical squamous cells of undetermined significance (ASC-US). All participants had at least one oncogenic HPV type at baseline. Three of five (60%) participants who regressed to AIN 1 or ASC-US became HPV-negative using DBH and real-time PCR, compared with none of 10 participants with no clinical response (P = 0.02). CONCLUSIONS: SGN-00101 was well tolerated in HIV-positive individuals, with preliminary evidence for clinical activity.

Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men.

OBJECTIVES: The incidence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of highly active antiretroviral therapy (HAART). The prevalence of the putative anal cancer precursor, anal intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced. We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART. DESIGN AND METHODS: A baseline point-prevalence analyses in a prospective cohort study of AIN was performed at a university-based research clinic. A total of 357 HIV-positive MSM with no history of anal cancer completed a questionnaire detailing behaviors and medical history, anal cytology and human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsy for detection of AIN. RESULTS: Eighty-one percent of participants with available CD4+ cell counts at baseline had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95% confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were associated with AIN after adjustment for length of time participants were HIV-positive, CD4+ cell count and HIV viral load. CONCLUSIONS: The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART. Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART.

A review of human papillomavirus vaccines: from basic science to clinical trials.

Human papillomavirus (HPV) infection leads to a spectrum of disease from genital warts to precancerous lesions to cervical and anal cancer and is a worldwide public health problem of epidemic proportions. Unique to HPV-related neoplasia, the presence of specific viral antigens such as the L1 capsid structural protein and the oncoproteins E6 and E7 provide opportunities for vaccine therapy. Although difficult to precisely define, the natural immune response to HPV is vitally important and defects in cell mediated immunity correlate with increased risk of disease and cancer. In preclinical animal models, both prophylactic and therapeutic vaccines have effectively induced HPV-specific cell mediated immune responses protecting animals from viral challenge or eliminating established tumors. Most prophylactic vaccines are virus-like particles (VLP) composed of the L1 structural protein. Phase I trials have demonstrated safety and immunogenicity, but limited efficacy data are available. Therapeutic vaccine trials are reviewed including E6 and E7 vaccines comprised of peptides, fusion proteins, encapsulated plasmid DNA, and recombinant vaccinia virus. All of the vaccines appear to be safe, well tolerated, and preliminary data indicates that most are clinically effective. Multiple trials are in progress and more mature data are expected within the next few years.

Anal cancer and its precursors in HIV-positive patients: perspectives and management.

Anal cancer is an increasing problem among HIV-infected persons. Although patients are living longer and with better quality of life because of treatment with HAART, they remain at risk for invasive anal cancer and its precursor, anal HSIL. Given the substantial numbers of patients with anal HSIL, further studies need to be done to determine the efficacy and optimal mode of treatment of HSIL, to define the optimal method for screening patients at risk, to define the best way to follow up patients with documented HSIL to ensure early detection, to define prognostic factors for progression to invasive cancer, and to determine the progression rate of HSIL to invasive cancer. Although patients with good functional status and immunologic function seem to do relatively well with standard CMT for anal cancer, there are less fortunate patients who experience substantial morbidity from therapy and have a poorer outcome. It is difficult to draw definitive conclusions about the therapy of HIV-positive patients with anal cancer based on the available literature because of the retrospective nature of the analyses, the small number of patients, and the heterogeneity of the patients reported with regard to tumor size, pretreatment immunologic status, and the variety of treatments received by patients in some series. Identifying patients who develop invasive anal cancer as early as possible will improve results to some degree, but prospective, controlled, multi-institutional trials evaluating the treatment of anal cancer in HIV-infected persons are required to accurately define ways to improve outcome with less morbidity. The results of ongoing therapeutic HPV vaccine trials are eagerly awaited. Improvement may come by the following, determining ways to more accurately stage patients, such as endoanal ultrasound, sentinel lymph node sampling, or positron emission tomography scans; defining the role of cisplatin and whether it is indeed less toxic and equally or more effective; consideration of continuous protracted infusion of low-dose 5-FU; the optimum use of growth factors; and an evaluation of the role of conformal radiotherapy or the use of radio-protectants, such as amifostine. Meanwhile, the best way to treat anal cancer in HIV-infected persons may be to prevent it from occurring by screening persons at risk and treating HSIL, or at a minimum, following up patients carefully and detecting cancers, if they occur, at the earliest possible time.

Incidence of and risk factors for type-specific anal human papillomavirus infection among HIV-positive MSM.

OBJECTIVE: HIV-positive MSM are at increased risk of anal human papillomavirus (HPV) infection compared with men in the general population, and little is known about the natural history of anal HPV infection in this population. The objective of this study was to determine the incidence of and risk factors for anal type-specific HPV infection. DESIGN: Prospective cohort study. METHODS: HIV-positive MSM were evaluated for anal HPV DNA, lifestyle factors, and sexual risk behaviors every 6 months for at least 2 years. RESULTS: The overall incidence rate of detectable type-specific anal HPV infection was 21.3 per 100 person-years [95% confidence interval (CI) 17.7-25.4] and was 13.3/100 person-years (10.5-16.6) for oncogenic HPV types. The most common incident infections were HPV 18 (3.7/100 person-years) and HPV 16 (3.5/100 person-years). An increased number of recent partners with whom the participant was the receptive partner [odds ratio (OR) 2.9 (1.6-5.1) 8+ partners vs. 0-1], an increased number of new partners in which the participant was the receptive partner [OR 1.03 (1.01-1.1) per partner], an increased number of new oral-anal contact partners in which the participant was the receptive partner [OR 1.1 (1.03-1.1) per partner], and the frequency of receptive anal intercourse [OR 1.1 (1.03-1.1) per act] all significantly increased the odds of incident HPV infection (P ≤ 0.05). CONCLUSION: HIV-positive MSM have a high incidence of oncogenic anal HPV infection. Recent receptive anal sexual behaviors, including receptive anal intercourse and receptive oral-anal contact, are the most important risk factors for incident anal HPV infection.

Presence of high-risk human papillomavirus genotype and human immunodeficiency virus DNA in anal high-grade and low-grade squamous intraepithelial lesions.

Human immunodeficiency virus type 1 (HIV)-infected individuals are at risk for anal cancer, which is caused by human papillomavirus (HPV). The relationship between HIV and HPV that leads to anal cancer remains unclear. Recent data, however, suggest that the continued persistence of HIV DNA in patients treated with combined antiretroviral therapy leads to progression of HIV disease and other HIV-associated complications. Therefore, we investigated the relationship among anal low- and high-grade squamous intraepithelial lesions (LGSIL/HGSIL), high-risk HPV genotypes, and high HIV DNA copy numbers. Anal cytology specimens were assayed for HPV genotype and HIV DNA copy number. High-risk HPV genotypes (odds ratio OR: 3.73; 95% confidence interval CI: 1.08-12.91; p=0.04) and high HIV DNA copy numbers (OR(per 100 HIV DNA copies): 1.13; 95% CI: 1.01-1.27, p=0.04) were both associated with LGSIL/HGSIL. When considering both high-risk HPV genotypes and HIV DNA copy numbers in predicting LGSIL/HGSIL, HIV DNA copy number was significant (OR(per 100 HIV DNA copies): 1.09; 95% CI: 0.96-1.23, p=0.04) but not high-risk HPV genotypes (OR: 2.30, p=0.28), which did not change when adjusted for nadir CD4 cell count and HIV RNA levels. The findings warrant further investigation of HIV DNA and its relationship with HPV in LGSIL/HGSIL pathogenesis.

Prevalence and risk factors for neutralizing antibodies to human papillomavirus types 16 and 18 in HIV-positive men who have sex with men.

OBJECTIVE: Human papillomavirus (HPV) vaccination is routinely recommended in HIV-positive men who have sex with men (MSM) aged ≤ 26 years. Levels of previous HPV exposure in older HIV-positive MSM are assumed to be too high to warrant routine HPV vaccination. However, little is known about the prevalence of and risk factors for neutralizing antibody seropositivity to HPV-16 or HPV-18, a key measure of previous exposure to these types. METHODS: Cross-sectional analysis of baseline visit for 296 HIV-positive MSM participating in a prospective cohort study of anal squamous intraepithelial lesions at a university-based research clinic. Participants completed a questionnaire detailing behaviors and medical history. Phlebotomy, anal cytology, HPV DNA testing with quantitation, and high-resolution anoscopy with biopsy were performed. A pseudovirion-based neutralizing antibody assay was used to measure HPV-16 and HPV-18 neutralizing antibodies. RESULTS: One hundred thirty-two of 296 (45%) men were HPV-16 seropositive and 141 of 296 (48%) were HPV-18 seropositive. One hundred seventy-five of 296 (59%) of the men were positive for HPV-16 antibodies or DNA and 167 of 296 (56%) were positive for HPV-18 antibodies or DNA. In multivariable analysis, HPV-16 seropositivity did not correlate with age, years of HIV positivity, CD4 level, or HIV viral load. Significant risk factors included HPV-16 DNA positivity with higher DNA levels (ptrend < 0.001) and higher number of receptive sexual partners in the last year (ptrend = 0.012). CONCLUSIONS: A high proportion of HIV-positive MSM aged >26 years are DNA negative and seronegative to HPV-16 and HPV-18 even when using a sensitive pseudovirion-based neutralizing antibody assay. Prospective studies are needed to determine the clinical- and cost-effectiveness of HPV vaccination in HIV-positive MSM aged >26 years.

Risk factors for anal human papillomavirus infection type 16 among HIV-positive men who have sex with men in San Francisco.

BACKGROUND: HIV-positive men who have sex with men (MSM) are at high risk of anal cancer compared with the general population. Human papillomavirus (HPV) infection, particularly HPV 16, is causally associated with anal cancer. However, the risk factors for anal HPV 16 infection are poorly understood. We determined the prevalence and risk factors for anal HPV 16 infection in a population of HIV-positive MSM, most of whom were being treated with antiretroviral therapy. DESIGN: Cross-sectional data from the baseline visit of a 4-year prospective cohort study. METHODS: Three hundred forty-eight HIV-positive MSM were recruited in San Francisco, and they received a detailed sexual behavior risk factor questionnaire. An anal swab was used to collect specimens for HPV type-specific DNA testing using L1 HPV DNA polymerase chain reaction. We used log-binomial multivariable models to determine the risk factors for anal HPV 16 infection. RESULTS: Ninety-two percent of HIV-positive MSM had at least 1 anal HPV type, 80% had at least 1 oncogenic HPV type, and 42% had HPV 16. Non-Hispanic white race and higher level of education were associated with a decreased risk of HPV 16 infection. A higher number of total male partners was associated with HPV 16 (relative risk: 1.6, 95% confidence interval 1.1 to 2.4, P = 0.01) for 201-1000 partners compared with 1-200. Injection drug use was independently associated with anal HPV 16 infection (relative risk: 1.5, 95% confidence interval 1.2 to 1.9, P = 0.003). CONCLUSIONS: The prevalence of anal HPV infection, including HPV 16, is high in HIV-positive MSM. HIV-positive MSM should be counseled about the risk associated with increased partners and injection drug use.

Infrared coagulator treatment of high-grade anal dysplasia in HIV-infected individuals: an AIDS malignancy consortium pilot study.

OBJECTIVE: To evaluate prospectively the safety of the infrared coagulator (IRC) as a treatment for anal high-grade squamous intraepithelial lesions (HSILs) in HIV-infected individuals and to seek preliminary evidence for efficacy. METHODS: HIV-infected patients with

High resolution anoscopy and targeted treatment of high-grade squamous intraepithelial lesions.

PURPOSE: The purpose of this video is to illustrate the use of high resolution anoscopy in the diagnosis and treatment of anal high-grade squamous intraepithelial lesions. METHODS: Five patients with anal dysplasia were examined in the operating room with acetic acid and the operative microscope. Lugol's solution was used selectively. Acetic acid is generously applied to aide in the recognition of high-grade squamous intraepithelial lesions. Acetowhite regions are examined under the operative microscope to further distinguish lesions as either low-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions. Acetowhite lesions with specific vascular characteristics like punctuate vessels or honeycomb patterns are highly suggestive of high-grade disease. These lesions are selectively destroyed under direct visualization with an effort to maintain normal mucosa and skin to prevent stenosis. Some pigmented lesions contain high-grade squamous intraepithelial lesions; the operative microscope is used in this setting to look for the vascular characteristics of high-grade disease. RESULTS: The video reports five male patients treated for high-grade squamous intraepithelial lesions with the aide of high resolution anoscopy. There were no intraoperative or postoperative complications. All lesions suspicious for high-grade squamous intraepithelial lesions based on observed vascular patterns were confirmed as such with permanent histopathology. CONCLUSION: The use of acetic acid and the operative microscope with selective use of Lugol's solution accentuates the visual characteristics of high-grade lesions, enhancing the surgeon's ability to target treatment to high-grade squamous intraepithelial lesions. High resolution anoscopy is useful in the targeted treatment of high-grade squamous intraepithelial lesions.

A serum-free Vero production platform for a chimeric virus vaccine candidate.

MedImmune Vaccines has engineered a live, attenuated chimeric virus that could prevent infections caused by parainfluenza virus type 3 (PIV3) and respiratory syncytial virus (RSV), causative agents of acute respiratory diseases in infants and young children. The work here details the development of a serum-free Vero cell culture production platform for this virus vaccine candidate. Efforts to identify critical process parameters and optimize culture conditions increased infectious virus titers by approximately 2 log(10) TCID(50)/ml over the original serum-free process. In particular, the addition of a chemically defined lipid concentrate to the pre-infection medium along with the shift to a lower post-infection cultivation temperature increased virus titers by almost 100-fold. This improved serum-free process achieved comparable virus titers to the serum-supplemented process, and demonstrated consistent results upon scale-up: Vero cultures in roller bottles, spinner flasks and bioreactors reproducibly generated maximum infectious virus titers of 8 log(10) TCID(50)/ml.