Anal cancer screening results from 18-to-34-year-old men who have sex with men living with HIV.

Men who have sex with men living with HIV (MSM LWH) are at highest risk for human papillomavirus (HPV)-associated anal cancer. There is no consensus on the optimal screening initiation age. This study aimed to assess the prevalence and severity of anal HPV disease among MSM LWH under the age of 35, which is a currently proposed screening age threshold. Between 2014 and 2020, 1255 18-to-34-year-old MSM LWH underwent anal cytology screening. 916 were co-tested for high-risk HPV (HR-HPV). 467 underwent high-resolution anoscopy (HRA) and biopsy. Cancer registry data were queried. Predictors of abnormal cytology (ie, ≥ASCUS) and histological high-grade squamous intraepithelial lesions (HSIL) were evaluated using unadjusted logistic regression models. Median age was 28 years (range, 18-34). 19% received at least one dose of HPV vaccine. Abnormal cytology rate was 65%. HR-HPV and HPV16 prevalence were 87% and 30%. Biopsy results were benign (10%), LSIL (43%) and HSIL (47%). No cases of prevalent or incident anal cancers were detected. Findings were similar between age subgroups (18-24, 25-29 and 30-34) except for a higher prevalence of AIN 3 in the 30-34 group (19%). Abnormal cytology was significantly associated with HR-HPV infection. Histological HSIL was associated with HR-HPV infection and cytological LSIL or worse. The absence of anal cancer in a large cohort of MSM LWH under the age of 35, despite high prevalence of anal HR-HPV infection and precancer, supports an age-based anal cancer screening strategy for MSM LWH.

Prevalence of anal high-risk human papillomavirus (HR-HPV) types in people living with HIV and a history of cancer.

This study aimed to describe the prevalence of high-risk human papillomavirus (HR-HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy. SETTING: Referral tertiary care hospital for adult patients with cancer. METHODS: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high-resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. RESULTS: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32-47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non-Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR-HPV infection was 89% (n=138) (95% CI 83-93) with at least one HR-HPV infection, and 62% (96) had coinfection with at least two types; the median HR-HPV types of coinfection were 3 (IQR 2-4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8-49.3), HPV 18 was 74 (47.7%, 95% CI 39.9-55.7) and with both 35 (22.6%). Some 59 patients (38%) had high-grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low-grade squamous intraepithelial lesions (LSIL). The prevalence of HR-HPV and HSIL among patients aged ≤35 and >35 years was the same. CONCLUSIONS: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR-HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy.

Anal intraepithelial neoplasia screening in women from the largest center for lower genital tract disease in China.

This study aimed to provide comprehensive clinical screening data for anal intraepithelial neoplasia (AIN). This study included 312 patients who underwent high-resolution anoscopy (HRA) examinations between January 1, 2020 and April 15, 2024. Clinical data, including demographic information, clinical history, cytology/high-risk human papilloma virus (hrHPV) results, and HRA records, were analyzed. The median age of all patients was 42 years (interquartile range: 33-52 years). Approximately 26.3% reported a history of VIN2/3+, 13.5% had a history of VaIN2/3+, 29.8% had a history of CIN2/3+, 44.6% had persistent cervical HPV16 infection, and 12.5% had immune suppression. Among the 312 patients, 14.4% were diagnosed with AIN2/3, 25.0% with AIN1 and 60.6% were normal. Anal cytological abnormalities were found in 41.3% of all patients, with a significantly higher rate in AIN2/3 patients than in ≤AIN1, 71.1% versus 36.3%, p < 0.001. The hrHPV positivity rate was 89.7%, with HPV16 being the most prevalent. The complete agreement rate for HRA impressions was 79.5%. Multi-variable analysis revealed immune suppression (odds ratio [OR]: 3.47, 95% confidence interval [CI]: 1.42-8.5) and VIN2/3+ (OR: 2.82, 95% CI: 1.27-6.28) were independent risk factors for AIN2/3. Abnormal cytology results (OR: 3.3, 95% CI: 1.52-7.17) and anal HPV16 infection (OR: 3.2, 95% CI: 1.26-8.12) demonstrated similar ORs for AIN2/3. Early screening for AIN2/3+ is crucial in Chinese women with lower genital tract precancerous and cancerous lesions, particularly in those with VIN2/3+ and immune suppression.

Surgical protocols for oral leukoplakia and precancerous lesions across three different anatomic sites.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. MATERIALS AND METHODS: A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. RESULTS: Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. CONCLUSION: There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.

Safety, feasibility, and short-term-outcome of anal endoscopic submucosal dissection for anal intraepithelial neoplasia: an option for focal lesions?

BACKGROUND: Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive anal cancer. AIN 2 (p16 positive) and AIN 3 are of high risk and should be treated because progression rates to anal cancer are around 10% and treatment significantly reduces this risk. The correct treatment is still a matter of debate. Human papilloma virus (HPV) plays a role in the development of AIN. Our aim was to assess anal endoscopic dissection (aESD) as an intervention for AIN3. METHODS: We retrospectively evaluated patients who underwent aESD for AIN 3 between December 2017 and March 2023. The interventional technique itself (duration, complications, size of specimen) and patient outcomes (recurrence, progression to anal cancer, re-intervention) were analyzed. RESULTS: Fifteen patients with a median age of 52 years (23-78) underwent aESD for AIN 3. All tested specimens were positive for HPV. Median duration of intervention was 56.1 min, one delayed postinterventional bleeding occurred, and specimen size was 12.05 cm2. Median follow-up was 11.17 months. Three recurrences (20%) appeared: one was resected via biopsy and two were again treated with aESD. There was no progression to invasive anal cancer in the follow-up period. CONCLUSIONS: Anal endoscopic submucosal dissection seems to be a safe and feasible treatment for AIN. Recurrences are seldom and can be treated again with the same method. Nevertheless, indications for resection in comparison to radiofrequency ablation, pharmacological therapy, and watch-and-wait strategy are still unclear. TRIAL REGISTRATION: Ethics commission of Salzburg, Austria, EK-Nr. 1056/2023. Keywords: Endoscopic submucosal dissection, anal intraepithelial neoplasia, anal cancer.

A nationwide longitudinal study on risk factors for progression of anal intraepithelial neoplasia grade 3 to anal cancer.

Little is known about risk factors for progression of high-grade anal intraepithelial neoplasia (AIN) to anal squamous cell carcinoma (ASCC). In this large, population-based study, we assess the role of factors related to immune status for the risk of ASCC among individuals from the general population with a diagnosis of AIN3. Individuals diagnosed with AIN3 during 1985-2016 were identified in the Danish Pathology Registry and followed for subsequent development of ASCC. The study population was linked to the National Patient Registry, the Danish Prescription Registry and the Danish HIV Cohort Study for information on autoimmune disease, genital warts and HIV status. To study the progression rate, Cox regression models with hazard ratios (HR) and 95% confidence intervals (CI) were applied with time since AIN3 as the underlying time scale and with adjustment for age at AIN3 diagnosis, year of AIN3 diagnosis and sex. The study population comprised 1222 individuals with AIN3 contributing 12 824 person-years of follow-up. Ninety-seven individuals (7.9%) developed ASCC. Individuals registered with an autoimmune disease or genital warts before and/or after the AIN3 diagnosis had an increased rate of progression to ASCC compared to individuals without these conditions. People living with HIV had a higher progression rate than HIV-negative individuals (HR = 4.25; 95% CI: 1.87-9.65) with the highest progression rate among those with CD4 count ≤200 cells/µL. These associations may be caused by an interplay between HPV infection and immunosuppression.

Cancer Risk Stratification of Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus-Positive Men by Validated Methylation Markers Associated With Progression to Cancer.

BACKGROUND: High-grade anal intraepithelial neoplasia (HGAIN; AIN2-3) is highly prevalent in HIV+ men, but only a minority of these lesions progress towards cancer. Currently, cancer progression risk cannot be established; therefore, no consensus exists on whether HGAIN should be treated. This study aimed to validate previously identified host cell DNA methylation markers for detection and cancer risk stratification of HGAIN. METHODS: A large independent cross-sectional series of 345 anal cancer, AIN3, AIN2, AIN1, and normal control biopsies of HIV+ men was tested for DNA methylation of 6 genes using quantitative methylation-specific PCR. We determined accuracy for detection of AIN3 and cancer (AIN3+) by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Methylation levels were assessed in a series of 10 anal cancer cases with preceding HGAIN at similar anatomic locations, and compared with the cross-sectional series. RESULTS: Methylation levels of all genes increased with increasing severity of disease (P < .05). HGAIN revealed a heterogeneous methylation pattern, with a subset resembling cancer. ZNF582 showed highest accuracy (AUC = 0.88) for AIN3+ detection, slightly improved by addition of ASCL1 and SST (AUC = 0.89), forming a marker panel. In the longitudinal series, HGAIN preceding cancer displayed high methylation levels similar to cancers. CONCLUSIONS: We validated the accuracy of 5 methylation markers for the detection of anal (pre-) cancer. High methylation levels in HGAIN were associated with progression to cancer. These markers provide a promising tool to identify HGAIN in need of treatment, preventing overtreatment of HGAIN with a low cancer progression risk.

Evaluating the efficacy of treatment options for anal intraepithelial neoplasia: a systematic review.

PURPOSE: Anal intraepithelial neoplasia (AIN) is the accepted precursor of anal squamous cell carcinoma (ASCC). There has long been a hypothesis that treating AIN may prevent ASCC. Many different treatment modalities have been suggested and studied. We conducted this systematic review to evaluate their efficacy and the evidence as to whether we can prevent ASCC by treating AIN. METHODS: MEDLINE and EMBASE were electronically searched using relevant search terms. All studies investigating the use of a single treatment for AIN that reported at least one end outcome such as partial or complete response to treatment, recurrence after treatment and/or ASCC diagnosis after treatment were included. RESULTS: Thirty studies were included in the systematic review investigating 10 treatment modalities: 5% imiquimod, 5-fluorouracil, cidofovir, trichloroacetic acid, electrocautery, surgical excision, infrared coagulation, radiofrequency ablation, photodynamic therapy and HPV vaccination. All treatment modalities demonstrated some initial regression of AIN after treatment; however, recurrence rates were high especially in HIV-positive patients. Many of the studies suffered from significant bias which prevented direct comparison. CONCLUSIONS: Although the theory persists that by inducing the regression of AIN, we may be able to reduce the risk of ASCC, there was no clinical evidence within the literature advocating that treating AIN does prevent ASCC.

Anal Squamous Intraepithelial Lesions (SILs) in Human Immunodeficiency Virus-Positive Men Who Have Sex With Men: Incidence and Risk Factors of SIL and of Progression and Clearance of Low-Grade SILs.

BACKGROUND: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at risk of anal squamous cell carcinoma. Data are limited on the natural history of the precursor to this carcinoma, anal squamous intraepithelial lesions (SILs). METHODS: HIV-positive MSM were screened for histopathological SILs by means of high-resolution anoscopy (HRA). For participants without SILs at baseline, we estimated the cumulative incidence and risk factors for SILs. For those with low-grade SILs (LSILs) at baseline, the risk of progression to high-grade SILs (HSILs) and the clearance rate were estimated at the lesion level. RESULTS: Of 807 men without SILs at baseline, 107 underwent follow-up HRA between 1 to 4.5 years later. At the second visit 18 men (16.8%) showed LSIL, and 25 (23.4%) HSIL. Age was associated with incident LSILs (adjusted odds ratio [aOR], 2.10 per 10-year increase in age; P = .01). Of 393 men with LSILs at baseline, 114 underwent follow-up HRA 0.5 to 2.5 years later. Of the 177 LSILs found at baseline, 87 (49.2%) had cleared at the second visit, and 29 (16.4%) had progressed to HSILs. CONCLUSION: Incident LSILs and HSILs were common during follow-up among HIV-positive MSM without dysplasia at baseline. Among men with LSILs at baseline, nearly half of these lesions cleared, and a small portion progressed.

HPV-associated anal lesions in HIV+ patients: long-term results regarding quality of life.

PURPOSE: HIV infection and concomitant HPV-associated anal lesions may significantly impact on patients' quality of life (QoL), as they are predicted to have negative effects on health, psyche, and sexuality. MATERIAL AND METHODS: Fifty-two HIV+ patients with HPV-associated anal lesions were enrolled in a survey approach after undergoing routine proctologic assessment and therapy for HPV-associated anal lesions if indicated over a time span of 11 years (11/2004-11/2015). Therapy consisted of surgical ablation and topic treatment. QoL was analyzed using the SF-36 and the CECA questionnaires. RESULTS: Fifty-two of 67 patients (77.6%) were successfully contacted and 29/52 provided full information. The mean age was 43.8 ± 12.8 years. The median follow-up from treatment to answering of the questionnaire was 34 months. Twenty-one percent (6/29) of the patients reported suffering from recurrence of condyloma acuminata, three patients from anal dysplasia (10.3%). In the SF-36, HIV+ patients did not rate their QoL as significantly different over all items after successful treatment of HPV-associated anal lesions. In the CECA questionnaire, patients with persisting HPV-associated anal lesions reported significantly higher emotional stress levels and disturbance of everyday life compared to patients who had successful treatment (71.9/100 ± 18.7 vs. 40.00/100 ± 27.4, p = 0.004). Importantly, the sexuality of patients with anal lesions was significantly impaired (59.8/100 ± 30.8 vs. 27.5/100 ± 12.2, p = 0.032). CONCLUSION: HPV-associated anal lesions impact significantly negative on QoL in HIV+ patients. Successful treatment of HPV-associated anal lesions in HIV+ patients improved QoL. Specific questionnaires, such as CECA, seem to be more adequate than the SF-36 in this setting.

Management of anal intraepithelial neoplasia and anal squamous cell carcinoma at a tertiary referral centre with a dedicated infectious diseases unit: an 18-year review.

INTRODUCTION: Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence rates. Risk factors include human immunodeficiency virus (HIV) infection, high-risk sexual activity and HPV-related genitourinary dysplasia/neoplasia. There is an overlap between high-risk patients and those attending HIV Medicine/Sexual Health (HMSH) services. We hypothesised that HMSH involvement may facilitate earlier referral to colorectal surgeons, with better outcomes. METHODS: Retrospective review of all ASCC and anal intraepithelial neoplasia (AIN) treated at a tertiary-referral hospital with a dedicated HMSH clinic between 2000 and 2018. Comparative analysis was performed of demographics, management and outcomes between HMSH and non-HMSH patients. RESULTS: One hundred and nine patients had anal pathology, eighty-five with ASCC (78%) and twenty-four with AIN (22%). Seventy (64%) were male. Median (range) age at ASCC diagnosis was 51 years (26-88). Thirty-six percent of all patients attended HMSH services, 28% were HIV positive, and 41% of males were men-who-have-sex-with-men (MSM). Eighty-one ASCC patients (97.5%) were treated with curative intent. Sixty-seven (80%) had primary chemoradiation therapy. Fifteen (17.5%) had primary surgical excision. Twelve (14%) developed recurrent disease. Ultimately, seven required salvage APR. Overall 3-year survival (3YS) was 76%. HMSH patients were significantly younger at ASCC diagnosis (p < 0.001), with a higher prevalence of HIV, HPV and MSM. HMSH attenders also tended to be diagnosed at earlier stages, were less likely to develop recurrence and achieved better overall outcomes, with a superior overall 3YS than non-HMSH patients (92% vs 72%, p = 0.037). CONCLUSION: ASCC incidence is increasing worldwide. The HMSH cohort has emerged as a distinct subpopulation of younger, high-risk, male patients. Collaboration between HMSH and colorectal surgeons offers an opportunity for risk reduction strategies and earlier intervention.

Anal squamous intraepithelial lesions: an update and proposed management algorithm.

The term anal squamous intraepithelial lesion (ASIL) is used to describe premalignant change of anal squamous cells that precede the development of squamous cell carcinoma. Pathophysiology is driven by the human papilloma virus (HPV), and progression and regression of ASIL being well described, with 12% of high-grade lesions progressing to invasive cancer within 5 years. Vaccination against HPV is effective for primary prevention. Management consists of identification and treatment of high-grade lesions to prevent progression to squamous cell carcinoma. Management of established ASIL aims to avoid the progression to invasive cancer and maintain fecal continence. A combination of surveillance, excision, ablative, or topical therapies is used to achieve this. The aim of the present study was to review the contemporary evidence about ASIL and to suggest a management algorithm.

Anal dysplasia and anal cancer. English version.

Anal intraepithelial neoplasia (AIN) and 89-100% of anal cancers are caused by persistent infections with high-risk (HR) human papillomaviruses (HPV). In HIV-positive patients, anal HPV infection and AIN are very common and these patients have a significantly increased risk for anal cancer. However, a continuous increase in the incidence of anal cancer has also been observed in the general population in recent decades. AIN can clinically present in diverse manners. In HIV-positive patients AIN can be hidden in condylomas. Approximately 3-14% of high-grade AIN progress to anal cancer within 5 years. Therefore, screening examinations should be offered to patients with an increased risk for anal cancer. The treatment options for AIN are similar to those for condylomas. HIV-positive patients with controlled immune status and HIV-negative patients with anal cancer respond comparably well to combined radiochemotherapy. A German-language S3 guideline for anal cancer will be available in 2020. In HIV-positive patients over 26 years of age, HPV vaccination showed no effect in a controlled phase­3 study. To prevent AIN and anal cancer in the future, HPV vaccination rates need to be increased in HPV-naïve girls and boys.

[Anal dysplasia and anal cancer]. / Anale Dysplasien und Analkarzinom.

Anal intraepithelial neoplasia (AIN) and 89-100% of anal cancers are caused by persistent infections with high-risk (HR) human papillomaviruses (HPV). In HIV-positive patients, anal HPV infection and AIN are very common and these patients have a greatly increased risk of developing anal cancer. However, a continuous increase in the incidence of anal cancer has also been observed in the general population in recent decades. AIN can clinically present in diverse manners. In HIV-positive patients AIN can be hidden in condylomas. Furthermore, 3-14% of high-grade AIN progress to anal cancer within 5 years. Therefore, screening examinations should be offered to patients with an increased risk for anal cancer. The treatment options for AIN are similar to those for condylomas. HIV-positive patients with controlled immune status and HIV-negative patients with anal cancer respond comparably well to combined radiochemotherapy. A German-language AWMF S3 guideline for anal cancer will be available in 2020. In HIV-positive patients over 26 years of age, HPV vaccination showed no effect in a controlled phase­3 study. To prevent AIN and anal cancer in the future, HPV vaccination rates need to be increased in HPV-naïve girls and boys.

Host Cell Deoxyribonucleic Acid Methylation Markers for the Detection of High-grade Anal Intraepithelial Neoplasia and Anal Cancer.

BACKGROUND: High-grade anal intraepithelial neoplasia (AIN2/3; HGAIN) is highly prevalent in human immunodeficiency virus positive (HIV+) men who have sex with men (MSM), but only a minority will eventually progress to cancer. Currently, the cancer risk cannot be established, and therefore all HGAIN is treated, resulting in overtreatment. We assessed host cell deoxyribonucleic acid (DNA) methylation markers for detecting HGAIN and anal cancer. METHODS: Tissue samples of HIV+ men with anal cancer (n = 26), AIN3 (n = 24), AIN2 (n = 42), AIN1 (n = 22) and HIV+ male controls (n = 34) were analyzed for methylation of 9 genes using quantitative methylation-specific polymerase chain reaction. Univariable and least absolute shrinkage and selection operator logistic regression, followed by leave-one-out cross-validation, were used to determine the performance for AIN3 and cancer detection. RESULTS: Methylation of all genes increased significantly with increasing severity of disease (P < 2 × 10-6). HGAIN samples revealed heterogeneous methylation patterns, with a subset resembling cancer. Four genes (ASCL1, SST, ZIC1,ZNF582) showed remarkable performance for AIN3 and anal cancer detection (area under the curve [AUC] > 0.85). ZNF582 (AUC = 0.89), detected all cancers and 54% of AIN3 at 93% specificity. Slightly better performance (AUC = 0.90) was obtained using a 5-marker panel. CONCLUSIONS: DNA methylation is associated with anal carcinogenesis. A marker panel that includes ZNF582 identifies anal cancer and HGAIN with a cancer-like methylation pattern, warrantingvalidation studies to verify its potential for screening and management of HIV+ MSM at risk for anal cancer.

Screening for anal cancer precursors among patients living with HIV in the absence of national guidelines: practitioners' perspectives.

PURPOSE: Immunocompromised populations including people living with HIV (PLWH) suffer disproportionate burden from anal cancer, a rare cancer caused by persistent infection of the anal canal with oncogenic strains of human papillomavirus. In the US, there are no nationally adopted screening guidelines for anal cancer. In the absence of such guidelines, this study explores healthcare practitioners' screening practices for early signs of anal cancer among PLWH. METHODS: Between November 2017 and June 2018, the research team completed 25 interviews among a diverse sample of healthcare practitioners who provide care for PLWH. RESULTS: Providers expressed frustration that screening and treatment guidelines for anal cancer were scant, and they varied in their screening practices. The majority of providers screened PLWH for anal dysplasia via the anal Pap smear; few providers were trained and had the medical equipment to conduct high-resolution anoscopy-guided biopsies, a more sensitive and specific screening method. Others screened through digital ano-rectal examinations (DARE) and both visually and with a DARE. Participants discussed how providers may be over-treating their patients who have high-grade anal intraepithelial neoplasia (AIN) and the role of biomarkers to determine whether the lesion is carcinogenic. CONCLUSIONS: Practitioners who provide care for PLWH are proactive in screening to help prevent and control anal cancer, a rare and slow-growing disease. Continuing to regularly surveil high-risk populations, particularly PLWH previously diagnosed with high-grade lesions, is critical to prevent and control anal cancer.

Second primary anal and oropharyngeal cancers in cervical cancer survivors.

BACKGROUND: Human papilloma virus infection is responsible for approximately 31,500 new cancers in the United States annually. Almost all cervical cancers are linked to human papilloma virus infection. As early identification and treatment of cervical cancer improve, the incidence of cervical cancer has decreased and survival has improved. However, survivors continue to remain at risk for other human papilloma virus-related malignancies. The purpose of this study was to assess the risk of primary anal and oropharyngeal cancers among women with a history of squamous cell carcinoma of the cervix. STUDY DESIGN: A population-based cohort of 21,060 women diagnosed with cervical squamous cell carcinoma from 1973 through 2014 was identified from the Surveillance, Epidemiology, and End Results Program-9 data. Standardized incidence ratios for anal and oropharyngeal cancers were calculated to estimate the risk of a second primary human papilloma virus-related malignancy based on incidence in the general population. Results were further stratified by age (20-53, 54 years old or older) and latency period (2-11, 12-59, 60-119, 120 months or longer). The number needed to screen for oropharyngeal and anal cancers was estimated using study results and Centers for Disease Control and Prevention-reported incidence rates. RESULTS: Cervical squamous cell cancer survivors had a higher risk of being diagnosed with oropharyngeal cancer (standardized incidence ratio, 4.36, 95% confidence interval, 1.19-11.15) and anal cancer (standardized incidence ratio, 2.20, 95% confidence interval, 1.28-3.52). Patients diagnosed with cervical cancer between ages 20 and 53 years had an increased risk of anal cancer (standardized incidence ratio, 3.53, 95% confidence interval, 1.15-8.23). Age 54 years or older at cervical cancer diagnosis was associated with increased oropharyngeal cancer risk only (standardized incidence ratio, 5.04, 95% confidence interval, 1.37-12.91). Latency stratification was significant for increased OPC risk between 2-11 months and 12-59 months after diagnosis. At 120 months or longer, there was an increased risk of both oropharyngeal cancer (standardized incidence ratio, 7.97, 95% confidence interval, 2.17-20.42) and anal cancer (standardized incidence ratio, 2.60, 95% confidence interval, 1.34-4.54). The estimated number needed to screen for oropharyngeal cancer (number needed to screen for oropharyngeal cancer, 282) and anal cancer (number needed to screen for anal cancer, 1272) is significantly less than the number needed to screen for cervical cancer. CONCLUSION: Squamous cell cervical cancer survivors have a substantially increased risk of anal and oropharyngeal cancers. This increased risk is significant 10 or more years after the cervical cancer diagnosis. Health care providers and survivors should be aware of this increased risk. The development of effective and economical surveillance methods for anal and oropharyngeal cancers in cervical cancer survivors is urgently needed.

Anal Intraepithelial Neoplasia Screening With Anal Pap Tests: Follow-up and Corresponding Histology.

BACKGROUND: Anal cytology is used as a screening tool in the detection of precancerous anal squamous lesions. Follow-up clinical examination after abnormal anal cytology is recommended. The objective of this study was to determine how often abnormal cytology was followed by a clinical examination at our institution and how often cytology predicted histologic outcome. MATERIALS AND METHODS: A retrospective chart review was performed (2008-2018) on patients with anal cytology, demonstrating either low-grade or high-grade squamous intraepithelial lesion. Clinical examination within 1 y (digital rectal examination, anoscopy, or high-resolution anoscopy) was recorded. The probability of anal intraepithelial neoplasm on biopsy after dysplasia on cytology was calculated, and McNemar's test was used to determine if there was correspondence between cytology and histology. RESULTS: A total of 327 anal cytology results demonstrated dysplasia (75% low grade and 25% high grade) in 182 patients. Seventy-five percent of dysplastic anal cytology were followed by clinical examination within 1 y, and 50% were biopsied. The probability of dysplasia on histology after dysplasia on cytology was 72% (95% confidence interval: 64%-78.5%). Twenty-eight percent of low-grade cytology results were upgraded to advanced disease (high-grade or invasive cancer) on histology. A low-grade cytology result was unable to preclude high-grade histology in our population. CONCLUSIONS: There is room for improvement at our institution to consistently follow-up with clinical examination after abnormal anal cytology. Our data suggest this is especially important considering anal cytology is an imperfect predictor of histologic anal intraepithelial neoplasia and invasive disease. Clinical examination is a critical component of anal dysplasia screening and follow-up.

Human papillomavirus infection in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These guidelines from the American Society of Transplantation Infectious Diseases Community of Practice update the epidemiology and management of human papillomavirus (HPV) infections in organ transplant recipients. HPV is one of the most common sexually transmitted infections and is associated with cancers of the anogenital region. Increasing evidence suggests an association with head and neck cancers as well. Solid organ transplant recipients have a higher risk of HPV infection than the general population. Infection manifests as premalignant lesions, warts, or cancer of the cervix, penis, vulva, scrotum, and anal canal. Most are asymptomatic initially, so diagnosis can be difficult without screening. A vaccine is available though not effective in preventing all cancer-causing strains. Organ transplant recipients should be screened for HPV-associated cancers and appropriate therapy initiated in a timely manner. Further studies are warranted to delineate the most effective screening methods and therapeutic modalities, including whether changes in immunosuppression are effective in attenuating disease.

Expectant management surveillance for patients at risk for invasive squamous cell carcinoma of the anus: a large US healthcare system experience.

PURPOSE: To determine the impact of expectant management surveillance for patients at risk for squamous cell carcinoma of the anus (SCCA). METHODS: Adult patients at risk for anal cancer, specifically those with human immunodeficiency virus (HIV) or known human papilloma virus (HPV) infections (anal dysplasia, anogenital warts, cervical dysplasia, or cervical cancer), underwent expectant management surveillance with targeted therapy of only grossly abnormal or symptomatic anoderm lesions. A retrospective analysis investigated the SCCA incidence in these surveilled populations and in the general population patients without known HIV or HPV infection. RESULTS: There were 452 incident SCCA in a population of 5,978,510 patients (mean follow-up per patient of 5.4 years). Four hundred ten cancers (90.7%) developed in 5,750,501 HIV-negative patients without documented history of HPV infection (cumulative incidence 0.007%). In at-risk patient populations, the cumulative incidence was 0.69% in patients with anal dysplasia (6 out of 872 patients), 0.14% in HIV+ patients (8 out of 5626 patients), and less than 0.1% in the remaining at-risk groups: cervical cancer (1 out of 1168 patients), cervical dysplasia (14 out of 125,604 patients), and genital warts (14 out of 94,739 patients). CONCLUSIONS: Expectant management surveillance, with targeted treatment for symptomatic or abnormal lesions, is an effective strategy for the diagnosis of anal cancer in at-risk patient populations. In this study, most patients who developed anal cancer had no known risk factors. A screening strategy for the general population needs to be further delineated.