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.
Abstract High Resolution Anoscopy (HRA) using a colposcope or operating microscope with 5% acetic acid and Lugol′s solutions was developed to identify abnormal epithelial changes such as high-grade ...squamous intraepithelial lesions (HSIL) and other lesions associated with human papillomavirus (HPV). It is hypothesized that targeted treatment of HSIL will prevent progression to cancer. HRA has become more accepted in clinical practice especially for populations considered at-risk for anal cancer including those who are immunocompromised and men who have sex (MSM). While data from prospective clinical trials designed to determine the effectiveness of HRA in preventing cancer are still pending, the procedure is now available 200 clinics worldwide. This article describes the procedure and identification of lesions for potential treatment.
This study explores provider preferences regarding anal cancer screening indications, initiation age, tools, and referral threshold to high resolution anoscopy (HRA).
International Anal Neoplasia ...Society affiliates were invited to complete an online survey. Options for initiation age and tools were delineated by sub-groups. HRA referral thresholds separately queried recommendations by patient immune status.
One hundred forty respondents participated. Although consensus was lacking with regard to specific screening initiation age, more respondents recommended younger initiation ages for men who have sex with men (MSM) living with HIV (LWH) compared with MSM not LWH (p < 0.01). “No age threshold” ranged 44-55% among sub-groups with lower genital tract disease. Cytology and digital anorectal exam (DARE) were the most frequently selected tools for all sub-groups (ranges 77-90% and 74-86%, respectively). HRA was recommended significantly more frequently for MSM LWH (58%) and patients with vulvar cancer (52%) compared to others (p < 0.01). “Any test abnormality” was more often selected as indication for HRA for immunocompromised (56%) and immunocompetent (46%) patients than a specific cytology test result (29%, 36% respectively).
Cytology and DARE were preferred screening tools; screening initiation age and HRA referral threshold showed less consensus. Evidence-based guidelines are needed and may lead to more consistent screening practices.
The aim of this study was to assess the probability of low-grade squamous intra-epithelial lesion (LSIL) regression in young women, and to examine the factors associated with this regression.
In a ...longitudinal study of human papilloma virus (HPV) infection, female adolescents aged 13–22 years were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the analysis, with regression defined as at least three consecutive normal Pap smears.
Median follow-up time from baseline (defined as the time of first LSIL diagnosis) for the 187 women with LSIL was 61 months (IQR 34–80). Median time they had been sexually active at diagnosis was 3·2 years (2·6–6·5). Probability of regression for the entire cohort was 61% (95% CI 53–70) at 12 months and 91% (84–99) at 36 months of follow-up. No associations were found between LSIL regression and HPV status at baseline, sexual behaviour, contraceptive use, substance or cigarette use, incident sexually transmitted infection, or biopsy. Multivariate analysis showed that only HPV status at the current visit was associated with rate of regression, whether infection was caused by one or more viral types (relative hazard=0·3 95% CI 0·21–0·42, and 0·14 0·08–0·25, respectively).
The high rate of regression recorded in this study lends support to observation by cytology in the management of LSIL in female adolescents. Negative HPV status was associated with regression, suggesting that HPV testing could be helpful in monitoring LSIL.
To evaluate the safety and efficacy of topical cidofovir for treatment of high-grade squamous perianal intraepithelial neoplasia (PAIN) and vulvar intraepithelial neoplasia (VIN) lesions in ...HIV-positive individuals.
Phase IIa prospective multicenter trial conducted at eight clinical sites through the AIDS Malignancy Consortium.
: HIV-positive patients with biopsy-proven high-grade PAIN that was at least 3 cm were enrolled. PAIN biopsy specimens were assessed for human papillomavirus (HPV) using PCR and type-specific HPV probing. Participants applied 1% topical cidofovir to PAIN and VIN (if present) for six 2-week cycles. Results were designated as complete response (CR), partial response (PR) (>50% reduction in size), stable disease, or progressive disease (PD).
Twenty-four men and nine women (eight with high-grade VIN as well) were enrolled. Mean age was 44 years and mean CD4 cell count was 412 cells/μl. HPV DNA (most commonly HPV16) was detected in all pretreatment study specimens. Twenty six (79%) participants completed treatment per protocol: CR, five (15%); PR, 12 (36%), stable disease, seven (21%); PD, two (6%) (one with a superficially invasive cancer and one with new area of high-grade PAIN). Treatment was well tolerated with most common adverse events being mild to moderate affecting lesional skin: pain/burning/irritation (25 patients) and ulceration (13 patients).
Topical cidofovir had 51% efficacy in the short-term treatment of high-grade PAIN and VIN with acceptable toxicity in HIV-positive individuals. Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed.
Objectives: The objectives of this study were to describe the early natural history of human papillomavirus (HPV) infection by examining a cohort of young women positive for an HPV test and to define ...within this cohort (1) the probability of HPV regression, (2) the risk of having a squamous intraepithelial lesion, and (3) factors that were associated with HPV regression.
Study design: The study was a cohort analytic design. An inception cohort of 618 women positive for HPV participated. HPV testing, cytologic evaluation, and colposcopic evaluation were performed at 4-month intervals. HPV testing was characterized for two groups: low risk (five types rarely associated with cancers) and high risk (nine types most commonly associated with cancers).
Results: Estimates provided by Kaplan-Meier curves showed that ~70% of women were found to have HPV regression by 24 months. Women with low-risk HPV type infections were more likely to show HPV regression than were women with high-risk HPV type infections (log rank test
p = 0.002). The relative risk for the development of high-grade squamous intraepithelial lesion (HSIL) was 14.1 (95% confidence interval: 2.3, 84.5) for women with at least three positive tests for high-risk HPV preceding the development of the HSIL compared with that for women with negative tests for high-risk HPV. However, 88% of women with persistent positive HPV tests have not had HSIL to date. No factors associated with high-risk HPV type regression were identified except for a negative association with an incident history of vulvar condyloma (relative risk = 0.5 95% confidence interval: 0.3 to 0.8).
Conclusion: Most young women with a positive HPV test will become negative within a 24-month period. Persistent positive tests with oncogenic HPV types represented a significant risk for the development of HSIL. However, we found that most young women with persistent positive HPV tests did not have cytologically perceptible HSIL over a 2-year period. Factors thought to be associated with the development of HSIL were found not to be important in HPV regression. (J Pediatr 1998;132:277-84)
The incidence of anal cancer in HIV-infected men who have sex with men (MSM) is highly elevated compared to the general population, as is the incidence of its precursor lesion, high-grade anal ...intraepithelial neoplasia (HGAIN). MSM in general and other immunocompromised populations are also at higher risk. Treatment of HGAIN may prevent development of cancer, similar to the decrease in cervical cancers that has occurred since the advent of cervical cancer screening programs in women. Cervical cancer screening tools have been adapted and validated for screening, diagnosis, and treatment of anal HGAIN. Anal cancer screening programs have now been available for more than a decade, although they are not yet standards of care. Incorporating screening procedures into practice depends on the available resources in a particular community. This article discusses the procedures for anal cancer screening including cytology, digital anal rectal examinations, high-resolution anoscopy, and biopsy.
BACKGROUND:Anal intraepithelial neoplasia (AIN) is common in men who have sex with men (MSM) and may be diagnosed by anal cytology screening.
METHODS:One hundred two MSM with clinician-collected anal ...cytology and histopathology specimens were assessed from a cohort study of AIN at the University of California at San Francisco. The men were given a cytology self-collection kit with written instructions for use and requested to collect the sample 1 month after the clinic visit.
RESULTS:Ninety-one percent of self-collected and 99% of clinician-collected anal cytology samples were adequate for interpretation. The sensitivity of abnormal anal cytology to detect AIN by histology was 68% in self-collected samples and 70% in clinician-collected samples, and the sensitivity to detect AIN 2 or AIN 3 was 71% and 74%, respectively. Cytologic results did not differ by grade between self-collected and clinician-collected samples. Among MSM diagnosed with AIN 2 or 3 by biopsy, 33% of self-collected and 39% of clinician-collected cytology samples were high-grade. The sensitivity of both self-collected and clinician-collected samples to detect AIN 2 or 3 was higher among HIV-positive MSM than among HIV-negative MSM.
CONCLUSIONS:MSM with biopsy-proven AIN can self-collect anal cytology samples with sensitivity comparable with that of experienced clinicians. This may facilitate screening for AIN.
To inform optimal approaches for detecting anal precancers, we performed a systematic review and meta‐analysis of the diagnostic accuracy of anal cancer screening tests in different populations with ...elevated risk for anal cancer. We conducted a literature search of studies evaluating tests for anal precancer and cancer (anal intraepithelial neoplasia grade 2 or worse, AIN2+) published between January 1, 1997 to September 30, 2021 in PubMed and Embase. Titles and s were screened for inclusion and included articles underwent full‐text review, data ion and quality assessment. We estimated the prevalence of AIN2+ and calculated summary estimates and 95% confidence intervals (CI) of test positivity, sensitivity and specificity and predictive values of various testing strategies, overall and among population subgroups. A total of 39 articles were included. The prevalence of AIN2+ was 20% (95% CI, 17‐29%), and ranged from 22% in men who have sex with men (MSM) living with HIV to 13% in women and 12% in MSM without HIV. The sensitivity and specificity of cytology and HPV testing were 81% and 62% and 92% and 42%, respectively, and 93% and 33%, respectively for cytology and HPV co‐testing. AIN2+ risks were similar among those testing positive for cytology, HPV, or co‐testing. Limited data on other biomarkers (HPV E6/E7 mRNA and p16/Ki‐67 dual stain), suggested higher specificity, but lower sensitivity compared with anal cytology and HPV. Our findings provide important evidence for the development of clinical guidelines using anal cytology and HPV testing for anal cancer screening.
What's new?
In order to develop global recommendations for anal cancer screening, a better understanding of anal precancer prevalence and screening effectiveness in different populations is needed. In this systematic review and meta‐analysis of 39 studies, overall prevalence of anal precancer was 20%. Screening typically involved anal cytology and high‐risk human papillomavirus (HPV) testing. Test sensitivity and specificity differed across groups, particularly for women, men who have sex with men living with HIV, and individuals without HIV. The findings can be used to support the development of anal cancer screening guidelines using cytology and HPV testing in different populations with increased anal cancer risk.
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.).
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