scholarly journals The Diagnostic Value of p16/Ki67 Dual Immunostaining for Anal Intraepithelial Neoplasia: A Meta-Analysis

2020 ◽  
Vol 14 (6) ◽  
pp. 155798832097763
Author(s):  
Cheng-Chieh Chen ◽  
Kuan-Chun Hsueh ◽  
Cheng-Huang Shen ◽  
Chyi-Huey Bai ◽  
Chia-Chang Wu ◽  
...  

The p16/Ki67 dual immunostaining was performed on anal cytology specimens; this is an anal cancer screening method. A literature search was performed in the BioMed Central, Cochrane Library, Embase, Google Scholar, and PubMed electronic databases for relevant articles. We included studies that discussed the efficacy of p16/Ki67 dual immunostaining for detecting anal intraepithelial neoplasia (AIN). Studies that calculated the diagnostic efficacy on a per-patient basis were included. We excluded review articles, case series, and studies that did not provide sufficient information. We extracted data on true positive, true negative, false positive, and false negative from the included studies to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). All analyses were performed with a random-effects model using MetaDiSc 1.4 and MetaDTA. The meta-analysis produced a pooled sensitivity of 0.63 (95% CI: 0.34, 0.86) and specificity of 0.65 (95% CI: 0.46, 0.81) for p16/Ki67 dual immunostaining in detecting AIN. The pooled DOR was 3.26 (95% CI: −0.29, 6.82). A subgroup analysis of HIV-infected men who have sex with men (MSM) demonstrated a pooled sensitivity of 0.75 (95% CI: 0.28, 0.96). p16/Ki67 dual immunostaining might have a higher sensitivity for detecting AIN in HIV-infected MSM. p16/Ki67 dual immunostaining might be more sensitive in HIV-infected MSM and has higher specificity compared to human papillomavirus testing among this high-risk group. p16/Ki67 dual immunostaining might be an adjuvant and potential triage test for anal cytology in anal cancer screening.

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 173
Author(s):  
Pino ◽  
Martí ◽  
Gaber ◽  
Svanholm-Barrie ◽  
Rodríguez-Carunchio ◽  
...  

There is growing interest in anal cancer screening strategies. However, cytological/molecular evaluation of anal samples is challenging. We aimed to determine the feasibility of detecting, in anal liquid-based cytologies, the expression of biomarkers involved in the cell cycle disturbance elicited by human papillomavirus (HPV). The accuracy of this approach in the identification of high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia grade2–3 (HSIL/AIN2–3) was also evaluated. 215 anal cytologies from men having sex with men living with human immunodeficiency virus were evaluated. Patients showing concordant cytological and anoscopy-directed biopsy diagnosis were selected: 70 with negative cytology and HPV test, 70 with low-grade SIL (LSIL/AIN1) cytology and biopsy, and 75 with cytology and biopsy of HSIL/AIN2–3. CDKN2A/p16, MKI67 and TOP2A mRNA expression was analyzed. HPV detection was performed with Xpert HPV Assay (Cepheid, Sunnyvale, CA, USA). HSIL/AIN2–3 showed higher expression for the biomarkers than LSIL/AIN1 or negative samples. The specificity for HSIL/AIN2–3 detection for a sensitivity established at 70% was 44.7% (95%confidence interval [CI] 36.5–53.2) for TOP2A and MKI67 and 54.5% (95%CI 46.0–62.8%) for CDKN2A/p16. mRNA detection of cell biomarkers in anal liquid-based cytology is feasible. Further studies are warranted to confirm if strategies based on mRNA detection have any role in anal cancer screening.


2019 ◽  
Vol 64 (4) ◽  
pp. 281-287 ◽  
Author(s):  
Andreia Albuquerque

The incidence and mortality of anal squamous cell carcinoma (SCC) are expected to continue to increase in the next 20 years. High-risk groups for anal SCC, i.e., human immunodeficiency virus (HIV)-positive patients, men who have sex with men (MSM), women with previous genital neoplasia, and solid-organ transplant recipients, have been identified. HIV-positive MSM have the highest risk, and some societies have advocated for anal cancer screening to be done in this population. Screening for anal SCC follows the same principles as that for cervical cancer since there are similarities between the two types of cancers. Anal cytology has been recommended as an initial screening method for high-risk groups, e.g., HIV-positive MSM. Normally, the cytology is liquid based and collected blindly by a clinician using a Dacron swab and it is especially used for internal lesions detection. The sensitivity to predict anal high-grade squamous intraepithelial lesions is higher in immunosuppressed patients with a high burden of the disease. The report should include the classification, normally according to the Bethesda terminology and the sample adequacy, in a manner similar to that for cervical cytology. In cases involving unsatisfactory samples, it is important to repeat the procedure given the prevalence of anal squamous cytological abnormalities in follow-up cytology procedures. The absence of transformation zone cells in anal cytology seems to increase the risk of false-negative results.


2020 ◽  
Vol 27 (1) ◽  
Author(s):  
E. Kaufman ◽  
C. De Castro ◽  
T. Williamson ◽  
B. Lessard ◽  
M. Munoz ◽  
...  

Background Anal cancer is potentially preventable through screening. For screening to be implemented, the screening procedures must be acceptable to the affected population. The objective of the present study was to measure the acceptability of currently available anal cancer screening tests in a population of women living with hiv who had experienced the tests.Methods The evva study (“Evaluation of Human Immunodeficiency Virus, Human Papillomavirus, and Anal Intraepithelial Neoplasia in Women”) is a prospective cohort study of adult women living with hiv in Montreal, Quebec. Participants were screened with cervical or anal hpv testing and cervical or anal cytology every 6 months for 2 years. High-resolution anoscopy (hra) and digital anal rectal examination (dare) were also performed systematically, with biopsies, at baseline and at 2 years. An acceptability questionnaire was administered at the final visit or at study withdrawal.Results Of 124 women who completed the acceptability questionnaire, most considered screening “an absolute necessity” in routine care for all women living with hiv [77%; 95% confidence interval (ci): 69% to 84%]. Yearly anal cytology or anal hpv testing was considered very acceptable by 81% (95% ci: 73% to 88%); hra every 2 years was considered very acceptable by 84% (95% ci: 77% to 90%); and yearly dare was considered very acceptable by 87% (95% ci: 79% to 92%). Acceptability increased to more than 95% with a longer proposed time interval. Pain was the main reason for lower acceptability.Conclusions Most participating women considered anal cancer screening necessary and very acceptable. Longer screening intervals and adequate pain management could further increase the acceptability of repeated screening.


Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1942 ◽  
Author(s):  
Andreia Albuquerque ◽  
Elisabete Rios ◽  
Fernando Schmitt

Clinicians are increasingly facing the decision of performing anal cancer screening in high-risk groups. Anal cytology is commonly the first approach. We systematically reviewed recommendations favoring anal cytology for anal cancer screening. Three databases were searched: PubMed, Scopus, and Embase, from January 2007 to 12 September 2019. The references cited by the retrieved articles and the websites of relevant organizations were also searched without language restrictions. Studies reporting guidelines from regional or national societies, institutes, or groups were included. Eight papers met the inclusion criteria and were selected, five were from the United States of America (USA) and three from Europe. There were no national recommendations published. There was one guideline specifically for solid-organ transplant recipients. The other seven targeted HIV-positive patients, with HIV-positive men who have sex with men (MSM) included as a screening group in all of these. Two recommendations favored screening in all HIV-positive patients. Five recommendations targeting HIV-positive patients made considerations about the cytology follow-up, recommending at least annual cytology in case of a normal result, and in case of squamous cytological abnormalities, a referral for anoscopy/high-resolution anoscopy. There were no recommendations for upper and lower age limits for screening. In conclusion, several societies recommend anal cancer screening using anal cytology in HIV-positive MSM patients. There is a lack of screening recommendations for other high-risk groups, with only one society recommending screening in transplant recipients.


Sexual Health ◽  
2013 ◽  
Vol 10 (6) ◽  
pp. 584
Author(s):  
Ana P. Ortiz ◽  
Humberto M. Guiot ◽  
Olga L. Díaz-Miranda ◽  
Leticia Romáán ◽  
Joel Palefsky ◽  
...  

Background Knowledge about epidemiology, diagnosis and treatment of anal neoplasia is limited among medical students and physicians from Puerto Rico (PR). Methods: Educational activity (1.5 contact hours) about anal cancer for a group of medical students, residents and faculty from the University of PR (n = 50). A 6-item pre- and post-test on anal cancer was given to assess the change in knowledge. Results: Thirty-four participants (68%) answered the survey. Overall, 78.8% had not received training in anal cancer screening and 93.9% were interested in receiving this training. Most (75.8%) were interested in participating in a clinical trial. An increase in the test scores was observed after the activity (pre-test: 3.4 ± 1.2; post-test: 4.7 ± 0.71). Three items showed an increment in the post-test that assessed participants’ knowledge regarding: (1) current status of guidelines for the screening/treatment of patients with HPV-related anal disease; (2) that anal intraepithelial neoplasia (AIN) 2 is considered to be a form of high-grade AIN (HGAIN); and (3) that warty growths in the anus are not necessarily a manifestation of HGAIN. Conclusions: This educational activity increased the participants’ knowledge of anal cancer and revealed that most of them were interested in future training and in collaborating in clinical trials. Training physicians from PR on anal cancer and clinical trials is essential to encourage recruitment of Hispanic patients in these studies now that the guidelines in anal cancer screening and treatment are on their way to being defined.


Sexual Health ◽  
2013 ◽  
Vol 10 (6) ◽  
pp. 588 ◽  
Author(s):  
Irving E. Salit ◽  
Sandra Blitz ◽  
Evan Collins ◽  
Banita Aggarwal ◽  
Janet Raboud ◽  
...  

Background Anal cytology (Pap tests) plus high-resolution anoscopy (HRA) as required are felt to be the optimal approach to anal cancer screening. We present preliminary results from STANDOUT, a study of acceptability and outcomes of anal cancer screening of HIV+ MSM in primary care practices. Methods: All previously unscreened HIV+ MSM from 9 HIV primary care practices, were invited by email or letter to receive anal cancer screening. Responders had anal cytology done at specially arranged or routine clinic visits. Those with high-grade squamous intraepithelial lesions (HSIL) on anal cytology were offered HRA to assess for anal intraepithelial neoplasia (AIN). Those with AIN 2/3 on biopsy were randomised to receive trichloroacetic acid (TCA) or infrared coagulator (IRC) treatments. Results: 1733 patients were invited and 921 (53%) agreed to have anal cytology done. Among those screened, 3 had unsatisfactory samples; 596 (65%) had normal cytology, 253 (27%) had low-grade squamous intraepithelial lesions (LSIL) and 69 (7.5%) had HSIL. HRA results are available in 64: 41 (64%) had histologic high-grade disease (29 had AIN2 and 12 had AIN3). Those with AIN 2/3 were randomised to receive treatment with TCA (16 patients) or IRC (18 patients). Treatment successes at 3 months were 6 of 15 patients for TCA (40%) and 11 of 16 patients for IRC (69%). Conclusions: In this sample of HIV+ MSM, about half of those invited for anal cancer screening agreed to have it done. Most with HSIL had histological high-grade disease and were treated. IRC was more successful than TCA at ablating high-grade disease.


Sexual Health ◽  
2019 ◽  
Vol 16 (1) ◽  
pp. 96 ◽  
Author(s):  
Joseph T. Hicks ◽  
Lu-Yu Hwang ◽  
Sarah Baraniuk ◽  
Margaret White ◽  
Elizabeth Y. Chiao ◽  
...  

Background Men who have sex with men (MSM) are at greater risk of developing anal cancer caused by human papillomavirus (HPV) than the rest of the general population. Currently, there are no formal national guidelines in the US advising men how and when to get anal cancer screening. We sought to assess differences in demographics, familiarity and anxiety about anal cancer among men who report having had anal cancer screening (i.e. anal cytology and/or a digital anorectal examination (DARE)). Methods: MSM were recruited to participate in a study to assess the feasibility of teaching self and partner anal examinations as a means of screening for anal cancer. Data for this secondary analysis were obtained using a written pre-test and a computer-assisted self-interview. Factors associated with screening were assessed with multivariable logistic regression to allow calculation of adjusted odds ratios (aORs). Results: Of the 197 participants with data, 145 (73.6%) reported having had anal cancer screening (either anal cytology, DARE or both) during their lifetime. Men who were younger, Black and HIV-negative were associated with decreased odds of reporting any type of anal cancer screening. For example, compared with White men, Black men were 80% less likely to report screening (aOR 0.2; 95% confidence interval (CI) 0.1–0.5). Self-perception of anal cancer knowledge was not associated with screening in multivariable analysis (aOR 1.6; 95% CI 0.6–3.9). Conclusions: Age, race and HIV status were independently associated with a history of anal cancer screening.


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