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![High-grade squamous intraepithelial lesion (HSIL/AIN-2/3) High-grade squamous intraepithelial lesion (HSIL/AIN-2/3). The highgrade lesion exhibits more severe atypia in the lower two-thirds or through the full thickness of the epithelium. There is loss of maturation, and nucleus-to-cytoplasm ratio is decreased. Nuclear membrane contours are irregular and chromatin is hyperchromatic. Disorganized growth is also noted. Increased mitotic activity in the mid to superficial aspects of the epithelium is a feature of HSIL (arrows). Inset: Immunoperoxidase stain for p16 a proxy test for presence of HPV. Diffuse dark nuclear and cytoplasmic staining is characteristic of HSIL (AIN2/3, bracket). Variable, mainly cytoplasmic staining is more typical of the LSIL as seen adjacent to the HSIL in this case (arrows). [H&E 600 x; inset 50 x]](publication/331140174/figure/fig2/AS:726744810135554@1550280873279/High-grade-squamous-intraepithelial-lesion-HSIL-AIN-2-3-High-grade-squamous.png)
High-grade squamous intraepithelial lesion (HSIL/AIN-2/3) High-grade squamous intraepithelial lesion (HSIL/AIN-2/3). The highgrade lesion exhibits more severe atypia in the lower two-thirds or through the full thickness of the epithelium. There is loss of maturation, and nucleus-to-cytoplasm ratio is decreased. Nuclear membrane contours are irregular and chromatin is hyperchromatic. Disorganized growth is also noted. Increased mitotic activity in the mid to superficial aspects of the epithelium is a feature of HSIL (arrows). Inset: Immunoperoxidase stain for p16 a proxy test for presence of HPV. Diffuse dark nuclear and cytoplasmic staining is characteristic of HSIL (AIN2/3, bracket). Variable, mainly cytoplasmic staining is more typical of the LSIL as seen adjacent to the HSIL in this case (arrows). [H&E 600 x; inset 50 x]
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Anal intraepithelial neoplasia (AIN) is a premalignant lesion for anal cancer. It is more commonly found in high-risk patients (e.g., human papilloma virus (HPV)/human immunodeficiency virus infections, post-organ transplantation patients, and men who have sex with men) and development is driven by HPV infection. The incidence of AIN is difficult t...
Contexts in source publication
Context 1
... cell atypia with nuclear enlargement and nuclear membrane contour irregularity with preserved nucleus-to-cytoplasm ratio (Fig. 1). HSIL involves the entire epithelium, or the lower two thirds, and is typified by a loss of maturation, nuclear hyperchromasia, and membrane irregularity, as well as a decrease in the nucleus-to-cytoplasm ratio (Fig. 2). Immunoperoxidase staining for p16 can assist in identifying dark nuclear and cytoplasmic staining in HSIL ...
Context 2
... have been no prospective studies examining the timeframe of follow up and, given the variable nature of AIN development into anal cancer, it is difficult to form established standardized guidelines. AIN-2/3). The high- grade lesion exhibits more severe atypia in the lower two-thirds or through the full thickness of the epithelium. ...
Citations
... In addition to clinical examination, multiple controversial clinical scoring systems have been developed to classify the severity of actinic keratoses [5]. While Cockerell et al. proposed to categorize AKs as keratinocytic intraepithelial neoplasia (KIN) [6], with regard to related types of intraepithelial neoplasia, like vulvar intraepithelial neoplasia (VIN) [7] or anal intraepithelial neoplasia (AIN) [8], Röwert-Huber et al. suggested a purely histologically based classification. According to this graduation, AKs were subdivided into three severity grades (AK I-III) based on the occurrence of atypical keratinocytes across different layers of the epidermis [9]. ...
Actinic keratoses (AKs) represent a common skin cancer in situ associated with chronic sun exposure. Early diagnosis and management of AKs are crucial to prevent their progression to invasive squamous cell carcinoma. Therefore, we investigated AK PRO score assessment using ex vivo confocal laser microscopy (EVCM) coupled with a novel fluorescent dye, FCF Fast Green, to explore its potential for the precise imaging and discrimination of collagen fibers. AK PRO assessment using EVCM demonstrated excellent conformity (95.8%) with histopathologic examination. The additional utilization of FCF Fast Green dye had no impact on AK visualization but showed a high affinity for collagen fibers enabling clear differentiation of collagen alterations between healthy and sun-damaged skin. The enhanced visualization of collagen fiber changes may aid clinicians in accurately identifying AKs and differentiating them from benign skin lesions.
... An important aspect of AK assessment is the use of a clinical scoring system to grade the severity of the lesions [4]. Much like other types of intraepithelial neoplasia, such as vulvar intraepithelial neoplasia (VIN) [5] or anal intraepithelial neoplasia (AIN) [6], Cockerell et al. categorized actinic keratoses (AKs) histologically as keratinocytic intraepithelial neoplasia (KIN) [2]. Another approach was suggested by Röwert-Huber et al. in 2007, where they proposed a purely histological classification. ...
Simple Summary
In this study, we evaluated the performance of a previous validated artificial intelligence-based assessment algorithm using line-field confocal optical coherence tomography (LC-OCT) to diagnose actinic keratosis (AK). The AI system accurately graded AK lesions in a large patient cohort and showed high agreement with visual assessments by experts. This non-invasive and fast AI-based approach has the potential to improve the efficiency and accuracy of AK diagnosis, leading to better clinical outcomes for patients.
Abstract
Actinic keratosis (AK) is a common skin cancer in situ that can progress to invasive SCC. Line-field confocal optical coherence tomography (LC-OCT) has emerged as a non-invasive imaging technique that can aid in diagnosis. Recently, machine-learning algorithms have been developed that can automatically assess the PRO score of AKs based on the dermo-epidermal junction’s (DEJ’s) protrusion on LC-OCT images. A dataset of 19.898 LC-OCT images from 80 histologically confirmed AK lesions was used to test the performance of a previous validated artificial intelligence (AI)-based LC-OCT assessment algorithm. AI-based PRO score assessment was compared to the imaging experts’ visual score. Additionally, undulation of the DEJ, the number of protrusions detected within the image, and the maximum depth of the protrusions were computed. Our results show that AI-automated PRO grading is highly comparable to the visual score, with an agreement of 71.3% for the lesions evaluated. Furthermore, this AI-based assessment was significantly faster than the regular visual PRO score assessment. The results confirm our previous findings of the pilot study in a larger cohort that the AI-based grading of LC-OCT images is a reliable and fast tool to optimize the efficiency of visual PRO score grading. This technology has the potential to improve the accuracy and speed of AK diagnosis and may lead to better clinical outcomes for patients.
... Risky anal intercourse behaviors include receptive anal intercourse, (1,2) number of sexual partners, (3,4) and age at first anal intercourse. (1,5) A recent meta-analysis reported the prevalence of HPV in relation to the severity of anal cytological abnormalities. (6,7) In addition, it was also reported that the incidence of AIN was higher in patients with HIV than in those without HIV. ...
... The prevalence of abnormal cytology was 32%, of ASCUS 17.56% and of LSIL 14.66%, but HSIL was not identified. The absence of HSIL detection in this study may be due to the limited sensitivity/ specificity for cytological detection of HSIL, (4) to the high false negative rate in patients with HIV infection (5) or to sampling factors. In this study, the proportion of participants with HIV was 62.66% with 70.8% having cytological abnormalities. ...
... However, in high-risk groups such as MSM, HIV or the immunocompromised, screening with anal cytology is still recommended. (5) The prevalence of abnormal cytology found in this study was lower than that of studies in India, (15) Taiwan, (11,14) Pakistan, (16) Thailand, (17) Australia, (18) and the United States of America. (19) In our study, we found that the prevalence of high-risk HPV was 82.35% for normal cytology, 76.92% for ASCUS and 81.81% for LSIL. ...
BACKGROUND
Anal human papillomavirus (HPV) is associated with the severity of anal cytologic abnormalities that are precancerous lesions. Knowledge of HPV type distribution in populations at risk for anal cancer is needed. This study investigated anal HPV infections and cytological abnormalities among men who have sex with men (MSM).
METHODS
A cross-sectional study was conducted involving 90 men aged >30 years with a history of anal sexual intercourse with men. Demographic characteristics and sexual behaviors were collected by using a self-completed questionnaire. Anal cytological results were examined, and HPV genotyping was performed by the Linear Array HPV genotyping test. Descriptive analyses of subject characteristics, prevalence, and 95% confidence intervals (CI) were performed. A chi-square test was used to determine their associations with high-risk HPV infection and cytological abnormalities.
RESULTS
The overall prevalence of abnormal cytology was 32% (24/75), atypical squamous cells of undetermined significance (ASCUS) 17.33 % (13/75), 14.66% (11/75) were classified as low-grade SIL (LSIL) and no participant had high-grade SIL (HSIL). Prevalence of HPV infection with normal cytology was 86.27% (44/51), ASCUS 92.30% (12/13), and LSIL 100% (11/11). The most common types of anal HPV in participants with cytological abnormalities are HPV 16, HPV 18 for high-risk HPV, and HPV 11, HPV 6 for low-risk HPV. There were no associations between the predictor variables and the abnormal cytology (p>0.05).
CONCLUSION
There was a high prevalence of HPV infection in MSM with abnormal anal cytology. A routine anal Pap smear program and vaccination are needed to prevent HPV infection and anal dysplasia in MSM.
... Tests for HPV DNA detection are the recommended primary tools for cervical cancer screening, 2 but their use in MSM living with HIV is under discussion mainly due to the high HPV infection prevalence. 3 There are numerous molecular tests available for HPV detection. Hybrid Capture 2 (HC2; Qiagen, Germany) and Linear Array Genotyping Test (LA; Roche Diagnostics, USA) have been widely validated in cervical samples 2 ; however, few studies have compared their performance in anal samples. ...
... The role of HPV DNA testing in AC screening programmes in people living with HIV or MSM is still under debate. 3 We identified that total HPV DNA detection demonstrated a high sensitivity but a low specificity for HGAIN, mainly as a consequence of the high prevalence of anal HPV . 7 In contrast to earlier studies, we identified that the use of HC2 versus LA showed higher specificity, PPV and area under the curve (AUC), while having a slight impact on sensitivity. ...
Background:
Incidence of anal cancer (AC) caused by persistent human papillomavirus (HPV) infection has risen in the last years in men who have sex with men (MSM) living with HIV. There is consensus that this population should be screened for anal precancerous lesions, but the role of HPV DNA testing in AC screening programmes is still under debate.
Objectives:
This study employed two molecular test to detect anal HPV DNA and compared assay performance and prognostic value for the diagnosis of histology proven high-grade intraepithelial anal lesions.
Methods:
MSM living with HIV attended their regular check-up visits consisting of detection of anal HPV infection, anal cytology, digital anorectal examination and high resolution anoscopy. HPV DNA was detected using Hybrid Capture 2 High-Risk test (HC2, total assay) and LINEAR ARRAY HPV Genotyping Test (LA, type-specific assay) RESULTS: Among 274 participant, prevalence of HPV DNA was 48.5% by HC2 and 89.4% by LA. HPV16 (30.6%) and HPV6 (19.6%) were the most common genotypes identified. Prevalence of multiple HPV infections was 56.2%. Agreement between HPV DNA assays was 75.2% (κ=0.51; 95% CI 0.42 to 0.60). Total HPV detection demonstrated high sensitivity (90%; 95% CI 68.3 to 98.8) and moderate specificity (58.4%; 95% CI 50.2 to 66.3), while type-specific HPV16/18 genotyping provided an increase in specificity and showed the highest area under the curve (0.81; 95% CI 0.74 to 0.89) and Youden's index (0.63).
Conclusions:
Both methodologies identified a high prevalence of anal HPV infection and multiple HPV infections in MSM living with HIV, showing a moderate overall agreement between them. Either total HPV detection or type-specific HPV16/18 detection together with a threshold ≥atypical squamous cells of undetermined significance for abnormal cytology showed an acceptable diagnostic accuracy.
... Topical treatments such as trichloroacetic acid, imiquimod, and 5-fluorouracil and ablative techniques such as fulguration with electrocautery or coagulation with infrared or laser are less invasive but carry a significant risk of recurrence. 12 Expectant management and watchful waiting by surveillance alone for HSIL/AIN-3 lesions expose patients to the risks of chemoradiation treatment if they convert to invasive anal cancer. ...
Background and Aims
The standard treatment for invasive squamous cell anal cancer is chemoradiation treatment. However, treatment options for high-grade dysplasia (squamous cell cancer in situ) are either surgical excision or topical treatment modalities. There are a few case reports, mainly from Japan, about resecting early squamous cell anal cancer (high-grade dysplasia/carcinoma in situ) by endoscopic submucosal dissection. We present a case series of 3 patients from a western hemisphere population with squamous carcinoma in situ of the anal canal resected with endoscopic submucosal dissection (ESD).
Methods
This is a retrospective series of 3 patients from a western hemisphere population with squamous carcinoma in situ of the anal canal resected with ESD. All patients were referred from the oncology team after declining surgical excision.
Results
Microscopically margin-negative en bloc resection was achieved in all patients. All patients were free from dysplasia or cancer on their latest endoscopic surveillance, ranging from 10 months to 26 months after ESD. One patient had a small lesion on follow-up 3 months after ESD that was removed by a curative EMR. There were no immediate or delayed adverse events.
Conclusions
ESD can be used to resect squamous cell carcinoma in situ of the anal canal. Larger studies with long-term follow-up are needed to evaluate the role of ESD in early squamous cell anal cancer and to compare it with other modalities of treatment.
... Anal intraepithelial neoplasia (AIN) is a premalignant lesion for ASCC. It is more commonly found in high-risk patients, including human immunodeficiency virus (HIV)-positive patients, post-organ transplantation patients and men who have sex with men (MSM) and its development is driven by human papillomavirus (HPV) infection, especially with high-risk serotypes (16 and 18) (2). ...
... risk sexual behavior (MSM, receptive anal intercourse or history of multiple sexual partners), post-organ transplantation patients or history of HPV-mediated genital cancers. (2,11) Diagnosis is made from cytology or biopsy. If cytology is positive for LSIL or HSIL, then patients should be referred for formal biopsy, usually performed via high-resolution anoscopy following application of acetic acid which will cause dysplastic cells to be more visible compared with surrounding tissue. ...
... Surgical excision is no longer recommended for AIN, since it is associated with significant morbidity (risk of stenosis or fecal incontinence) and patients can still have recurrences. (2,11) ESD is a minimally invasive approach that has demonstrated safety and effectiveness in the treatment ...
Anal intraepithelial neoplasia is a premalignant lesion for anal squamous cell carcinoma. Current treatment options, consisting of topical therapy and local ablative procedures with electrocautery or radiofrequency ablation, are effective although recurrence rates are high. Experience with endoscopic submucosal dissection for anal lesions is limited, with only a few cases of anal intraepithelial neoplasia and early anal squamous cell carcinoma. We present a 65-year-old woman with high-grade anal intraepithelial neoplasia successfully removed by endoscopic submucosal dissection with no complications or signs of recurrence after 5 months, suggesting that this technique could be a safe and effective approach for management of anal premalignant lesions.
... [1][2][3] Many practicing proctologists disagree on timing and method of surveillance for AIN. 4,5 We hypothesize that the rate of progression from AIN to ACSS is very low in a general population undergoing surveillance for AIN without high-resolution anoscopy. ...
... The method of surveillance, treatment, and the progression rate of AIN to ASCC is variable within the literature. [4][5][6] We looked at the rate of progression to ASCC in a population undergoing surveillance every 3-6 months with anoscopy and treatment with topical treatments and excision/ fulguration. Our cumulative incidence of ASCC is 0.6% in compliant patients compared to 2.8% in noncompliant patients. ...
... Among these, HPV 16 is the most frequent type and is considered a crucial factor for the development of squamous cell carcinoma [5]. Anal intraepithelial neoplasia and anal squamous intraepithelial lesions are considered premalignant signs of anal squamous cell carcinoma, which is driven by HPV infection [6]. Another risk factor is immunosuppression caused by acquired immune deficiency syndrome caused by human immunodeficiency virus (HIV) infection [7]. ...
Background
Anal squamous cell carcinoma accounts for less than 2-3% of all digestive system carcinomas. The present study aimed to determine the clinical characteristics, treatment patterns, and treatment outcomes of patients at our institution.
Methodology
We reviewed the clinical data of all consecutive patients with anal squamous cell carcinoma who were treated with definitive radiotherapy in our department between July 2009 and July 2020. Radiotherapy was delivered in 1.8-2 Gy daily fractions to a whole pelvic dose ranging from 45 to 50 Gy, followed by boost radiotherapy of 10-15 Gy, resulting in a total dose of approximately 60 Gy. Concurrent chemotherapy with radiotherapy included 5-fluorouracil/mitomycin C or 5-fluorouracil/cisplatin.
Results
A total of 14 patients with a median age of 61.5 years (range: 45-85 years) were analyzed. There were nine women and five men. The clinical T stage was T1 in two patients, T2 in six patients, T3 in two patients, and T4 in four patients. The clinical N stage was N0 in four patients and N1 in 10 patients. Patients with clinical stage III disease comprised 79% of the entire study population. For the entire cohort, the five-year overall survival rate was 83.3% and the five-year progression-free survival rate was 48.5%. One patient experienced grade 3 fecal incontinence, and the others experienced no radiation-induced severe delayed adverse events.
Conclusions
The results of our study demonstrated that definitive radiotherapy with or without chemotherapy for patients with anal squamous cell carcinoma is an effective and feasible treatment.
... Several other HR-HPV genotypes were relatively common in our cohort, regardless of HIV status. Importantly, only three participants (two living with HIV, and one not) were infected with all four HPV genotypes that are targeted by the quadrivalent vaccine (HPV- 6, 11, 16 and 18) while no participant was infected by all nine genotypes targeted by the nonavalent vaccine (HPV- 6,11,16,18,31,33,45, 52 and 58). ...
Men who have sex with men (MSM) are disproportionately affected by anal cancer, predominantly caused by high-risk (HR) human papillomavirus (HPV) infection. Currently, the nonavalent HPV vaccine provides coverage against nine HPV genotypes, including seven HR-HPV genotypes. Here, we characterize anal HR-HPV genotype distribution and associated risk factors in MSM from Toronto, Canada recruited between September 2010 and June 2012. Wilcoxon–Mann–Whitney test was used for continuous variables, Chi-square test was performed for categorical variables, and a multivariable model using logistic regression was created to assess for correlates of anal HR-HPV infection. A total of 442 MSM were recruited, with a median age of 45 (IQR 38–50) and an overall HPV prevalence of 82%. The prevalence of any HR-HPV infection was 65.3% and 50.7% in the HIV-positive and HIV-negative MSM, respectively. No participant tested positive for all genotypes covered by the nonavalent vaccine. HIV status (aOR 1.806; 95% CI 1.159–2.816), smoking (aOR 2.176; 95% CI 1.285–3.685) and the number of lifetime sexual partners (aOR 2.466; 95% CI 1.092–5.567) were independent risk factors for anal HR-HPV infection. Our findings will be useful to inform HPV vaccine rollout and HPV prevention strategies in Canadian MSM.
... Despite increasing incidence, it is unclear whether systematically screening WLWH is an effective cancer prevention strategy (Goedert et al., 2016;Moscicki et al., 2015). Anal cancer progresses in a similar fashion to cervical cancer and can be screened using similar modalities such as Papanicolaou (Pap) tests (Siddharthan et al., 2019). Similar to a cervical Pap, anal Pap results can be normal, atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSILs) or high-grade squamous intraepithelial lesions (HSILs); and anal histology results may range from normal, anal intraepithelial neoplasia (AIN) low grade (AIN-1) or high grade (AIN-2/3) from directed biopsies. ...
Women living with HIV (WLWH) are at increased risk of anal cancer compared to women without HIV, often due to persistent human papillomavirus (HPV) infections. This paper describes current practices and challenges conducting anal cancer screening for WLWH at an urban integrated safety-net system and a non-profit community-based HIV clinic. We conducted 25 semi-structured interviews with clinical and administrative stakeholders to assess knowledge, clinic practices and procedures, and experiences with anal cancer screening. Interview transcripts and fieldnotes were thematically analyzed using an iterative deductive and inductive coding scheme. Findings were organized by the Consolidated Framework for Implementation Research (CFIR) domains and constructs. Provider-level barriers to conducting anal cancer screening included limited knowledge of guidelines. System-level barriers included: structural characteristics such as lack of coordination between clinics to discern provider roles and responsibilities; and limitations in available resources such as configuration of electronic health records and infrastructure to manage referrals of abnormal anal Pap results. We conclude that anal cancer screening and follow-up for WLWH requires organization and coordination between multiple care teams, updated clinical information systems to facilitate communication and support anal Pap ordering and result documentation, and infrastructure that includes policies and protocols for management of abnormal results.
Trial registration: ClinicalTrials.gov identifier: NCT02135419.
