The risk for acquiring human papillomavirus (HPV) infections and associated diseases is lifelong. An important part of prophylactic HPV vaccine development is durable protection against infection and ...disease. With comprehensive long-term follow-up (LTFU) in adolescents, men, and women, the quadrivalent HPV (qHPV) vaccine demonstrated durable effectiveness, immunogenicity, and safety, with almost no breakthrough disease. Those who received a placebo during initial trials were offered the qHPV vaccine at study conclusion and continued to be followed in LTFU extensions. In this catch-up vaccination group, LTFU demonstrated protection even in individuals with current or prior HPV infection after approximately 3 years. The initial efficacy and durable long-term effectiveness of the qHPV vaccine have already translated to a real-world reduction in cancer and cancer precursors. To date, there is no evidence of waning protection; evidence suggests that vaccination ultimately provides strong protection against future disease, with effective prophylaxis even among those with past infections.
Although the incidence of many cancers is decreasing in the United States, the incidence of anal squamous cell cancer is increasing, and mortality appears to be outpacing the increased incidence in ...the number of new cases. Furthermore, patients are presenting with more advanced disease.
We previously reported on infrared coagulator ablation of anal high-grade intraepithelial squamous lesions in HIV-positive and HIV-negative men who have sex with men (MSM) with a median follow-up of ...1.5 years.
We sought to determine high-grade intraepithelial squamous lesion recurrence rates after long-term follow-up for infrared coagulator ablation, and whether patients progressed to invasive cancer.
: This study investigated a retrospective cohort.
This study was set in an office-based practice.
The patients evaluated were MSM who underwent at least 1 infrared coagulator anal high-grade intraepithelial squamous lesion ablation between 1999 and 2005 with at least 1-year additional follow-up.
Infrared coagulator ablation had been performed.
The primary outcomes measured were high-grade intraepithelial squamous lesion recurrence and progression to anal squamous-cell carcinoma.
Ninety-six MSM were included (44 HIV-positive) with a median follow-up of 48 and 69 months in HIV-negative and HIV-positive MSM. Thiry-five percent of HIV-positive and 31% of HIV-negative subjects from the original cohort were lost to follow-up. In HIV-negative MSM, 32 (62%) had a recurrence in a mean of 14 months. Recurrence rates after the second and third treatments were 48% and 57%. In HIV-positive MSM, 40 (91%) had a recurrence in a mean of 17 months. Recurrence rates after the second, third, and fourth infrared coagulator ablations were 63%, 85%, and 47%. After the first ablation, HIV-positive MSM were 1.9 times more likely to have a recurrence than HIV-negative MSM (P = .009). One year after the first ablation, 61% of HIV-positive MSM had recurrent high-grade intraepithelial squamous lesions in comparison with 38% of HIV-negative MSM. One year after the second ablation, 49% of HIV-positive MSM had recurrent high-grade intraepithelial squamous lesions in comparison with 28% of HIV-negative MSM. In HIV-negative and HIV-positive MSM, the probability of curing an individual lesion after first ablation was 80% and 67%. Most recurrence was due to the development of metachronous lesions occurring in 82% and 52% of HIV-positive and HIV-negative subjects after their first infrared coagulator treatment. The mean number of recurrent lesions for both HIV-positive and HIV-negative MSM was never >2. No MSM developed squamous-cell carcinoma, and there were no serious adverse events. At last visit, 82% of HIV-positive MSM and 90% of HIV-negative MSM were high-grade intraepithelial squamous lesion free.
This was a retrospective, observational study with significant loss to follow-up.
Infrared coagulator ablation is an effective treatment for high-grade intraepithelial squamous lesions, and no patients progressed to cancer. HIV-positive patients are significantly more likely to have a recurrence, and recurrence occurred more rapidly in these patients. Continued follow-up is important.
The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is ...preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.
We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer.
Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval CI, 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test).
Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).
The quadrivalent human papillomavirus vaccine (qHPV) is FDA-approved for use in males 9 to 26 years old to prevent anogenital condyloma. The objective of this study is to determine if qHPV is ...effective at preventing anal condyloma among men who have sex with men (MSM) aged 26 years and older.
This post-hoc analysis of a nonconcurrent cohort study evaluated 210 patients without history of anal condyloma and 103 patients with previously-treated anal condyloma recurrence-free for at least 12 months prior to vaccination/time zero. We determined the rate of anal condyloma development in vaccinated versus unvaccinated patients.
313 patients with mean age 42 years were followed for median 981 days. During 773.6 person-years follow-up, condyloma developed in 10 (8.6%) vaccinated patients (incidence of 3.7 per 100 person-years) and 37 (18.8%) unvaccinated patients (incidence 7.3 per 100 person-years; p = 0.05). Multivariable hazards ratio showed that qHPV was associated with decreased risk of anal condyloma development (HR 0.45; 95% CI 0.22-0.92; p = 0.03). History of anal condyloma was associated with increased risk of anal condyloma development (HR 2.28; 95% CI 1.28-4.05; p = 0.005), as was infection with oncogenic HPV (HR 3.87; 95% CI 1.66-9.03; p = 0.002).
Among MSM 26 years of age and older with and without history of anal condyloma, qHPV reduces the risk of anal condyloma development. A randomized controlled trial is needed to confirm these findings in this age group.
Background. Most squamous cell anal cancers and precancerous lesions are attributed to human papillomavirus (HPV) infection. By preventing HPV infection, quadrivalent HPV vaccine (qHPV) reduces risk ...of anal cancer/precancerous lesions in young men who have sex with men (MSM) without history of anal cancer/precancerous lesions. In our practice, many persons with history of precancerous anal lesions or high-grade anal intraepithelial neoplasia (HGAIN) have been vaccinated electively. We determined whether qHPV is effective at preventing recurrence of HGAIN. Methods. This nonconcurrent cohort study evaluated 202 patients with a history of previously treated HGAIN. Eighty-eight patients were vaccinated, and 114 patients were unvaccinated. We determined the recurrence rate of histologic HGAIN in vaccinated versus unvaccinated patients. Results. During 340.4 person-years follow-up, 12 (13.6%) vaccinated patients and 35 (30.7%) unvaccinated patients developed recurrent HGAIN. Multivariable hazards ratio (HR) analysis showed testing positive for oncogenic HPV genotypes within 8 months before study entry was associated with increased risk of recurrent HGAIN at 2 years after study entry (HR 4.06; 95% confidence interval CI, 1.58-10.40; P = .004), and qHPV was associated with decreased risk of recurrent HGAIN (HR .50; 95% CI, .26-.98; P = .04). Among patients infected with oncogenic HPV, qHPV was associated with decreased risk of recurrent HGAIN at 2 years after study entry (HR .47; 95% CI, .22-1.00; P = .05). Conclusions. qHPV significantly reduces HGAIN recurrence among MSM and may be an effective posttreatment adjuvant form of therapy. A randomized controlled trial is needed to confirm these results.
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.
High-grade dysplasia is the anal carcinoma precursor. Clinicians ablate high-grade dysplasia with laser, electrocautery, and infrared coagulation to prevent cancer.
The aim of this study was to ...determine the long-term effectiveness of high-grade dysplasia ablation and the incidence of cancer.
This study is a retrospective chart review of patients who were treated for high-grade dysplasia from February 1998 until May 2012.
This study was conducted in a surgical practice screening patients for anal cancer and high-grade dysplasia.
The patients identified were HIV-positive and -negative men who have sex with men.
The ablation of high-grade dysplasia was performed.
The primary outcomes measured were the probability of high-grade dysplasia recurrence postablation and the incidence of cancer.
Four hundred fifty-six HIV-positive men who have sex with men (mean age, 45 ± 9 years) and 271 HIV-negative men who have sex with men (mean age, 41 ± 11 years) followed for a median of 2.2 (range, 0.2-13) years underwent high-grade dysplasia ablation by laser, infrared coagulation, and/or electrocautery. Median time to recurrence was 6.8 and 6.9 months for HIV-positive and -negative patients. Kaplan-Meier curves predict a rate of recurrence 1 year after the first ablation for HIV-positive and -negative patients of 53% (95% CI, 49%-58%) and 49% (95% CI, 43%-55%). At 2 and 3 years, the rate of recurrence was 68% (95% CI, 63%-73%) and 77% (95% CI, 7%2-82%) for HIV-positive patients and 57% (95% CI, 51%-64%) and 66% (95% CI, 59%-73%) for HIV-negative patients. The median number of recurrent lesions was ≤2 for HIV-positive patients and ≤1 for HIV-negative patients. Recurrence increased with HIV infection (HR, 1.3; 95% CI, 1.1-1.6) and each additional lesion treated (HR 1.6, 95% CI, 1.1-1.2). Five HIV-positive men who have sex with men developed cancer. The Kaplan-Meier probability of cancer 3 years postablation was 1.97% (95% CI, 0.73%-5.2%).
This is a retrospective study by 1 surgeon who has extensive experience treating anal dysplasia. There was no pathology review, and the type of recurrence cannot be definitively determined because the location could be inaccurate.
Patients undergoing ablation of intra-anal high-grade dysplasia have high recurrence, but the probability of developing anal cancer is low. HIV infection and increased number of high-grade dysplasias increases the risk of recurrence.
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