Immunoreactivity of p16 in anal cytology specimens

Darvishian, Farbod; Stier, Elizabeth A.; Soslow, Robert A.; Lin, Oscar

doi:10.1002/cncr.21711

Cited by 18 publications

(23 citation statements)

References 42 publications

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“…A few biomarkers have been investigated as adjunctive means to enhance the diagnostic accuracy of anal pathology specimens (15,(28)(29)(30)(31). The p16 protein (also known as p16 INK4a , MTS1, and CDKN2) is a common target of inactivation in human cancers but is overexpressed in high-risk HPV-related cervical cancers (32)(33)(34) and anal cancer (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…Diffuse strong immunohistochemical staining for p16(INK4a) suggests integration of high-risk HPV DNA into the host genome and has been strongly associated with CIN 2/3 (35), high-grade AIN (15,16), and anal cancer (36). The sensitivity and specificity of immunohistochemical detection of p16 in anal cytology specimens are not high (29). We used anal swabs to detect biomarkers; in clinical practice, procuring those samples is less labor intensive and may be less subject to diagnostic biases than histochemical staining.…”

Section: Discussionmentioning

confidence: 99%

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Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

Salit

Tinmouth

Chong

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: HIV-positive men with a history of analreceptive intercourse are at risk for anal cancer. We determined whether human papilloma virus (HPV) biomarkers were correlated with anal pathology in these men. Methods: HPV genotype was determined by PCR/line blot assay. Real-time PCR assays were done for viral load, E6 transcripts for HPV genotypes 16, 18, and 31, and p16 transcripts. Results: The most common oncogenic HPV types were HPV 16 (38%), 18 (19%), 45 (22%), and 52 (19%). HPV types 16, 18, 31, 52, 59, and 68 were associated with highgrade histology. The number of HPV genotypes per anal swab was higher for anal intraepithelial neoplasia (AIN) 2/3 than for normal or AIN 1 histology [median, 5 types (interquartile range) (IQR), 3-7 versus 3.5 (IQR), 2-6; P = 0.0005]. HPV 16 viral load was also associated with

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

Salit

Tinmouth

Chong

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…17 The specific surveillance programs used to monitor high-risk patients vary from 1 center to another, but typically include periodic anorectal pap smear screening, preferably with ThinPrep specimens, and high resolution anoscopy with perianal mapping for all HSIL. [18][19][20][21] In our center, patients are treated by high-resolution anoscopy and targeted ablation using an infrared coagulator. Punch biopsy mapping followed by wide local excision, the more traditional approach to anal canal dysplasia, is reserved for more intractable or extensive disease.…”

Section: Who Is At Risk?mentioning

confidence: 99%

Diagnostic Problems in Anal Pathology

Longacre¹,

Kong²,

Welton

2008

Advances in Anatomic Pathology

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Anal squamous cell carcinoma and its precursor lesions are increasing in incidence in the United States and Europe. This trend predates human immunodeficiency virus/acquired immune deficiency syndrome and has been associated with persistent high-risk human papilloma virus (HPV) genotype infection, previous lower genital tract dysplasia/carcinoma, high frequency anoreceptive intercourse, heavy cigarette smoking, immunosuppression in solid organ transplant and immune disorders, and human immunodeficiency virus seropositivity. Screening protocols for at-risk patients are under active investigation and pathologists are often asked to assess anal canal and perianal biopsies for the presence of dysplasia and/or invasive carcinoma. Because underdiagnosis and overdiagnosis of anal cancer and precancer may lead to inappropriate treatment, it is important for the pathologist to be aware of current screening strategies, specific risk lesions, and the role of pathology in initial diagnosis and evaluation of anal biopsy and/or resection specimens. Standardized histologic criteria and uniform terminology should be used for reporting all anal canal and perianal squamous intraepithelial lesions. HPV subtyping, anal cytology, and recently identified biomarkers, such as p16 and Becton Dickinson ProEx C may provide additional information in problematic cases, but it is important to be aware of the limitations of these assays. HPV has been linked to all the major histologic subtypes of anal carcinoma (eg, basaloid, cloacogenic, transitional, etc.) and this association is strongest for anal canal lesions. With the possible exception of the microcystic pattern, histologic subtype does not seem to predict prognosis; and anal squamous cell carcinomas should be classified as either keratinizing or nonkeratinizing. Poorly differentiated squamous cell carcinomas have a worse prognosis and should be distinguished from poorly differentiated adenocarcinoma, melanoma, and neuroendocrine tumors. Very well differentiated squamous cell carcinoma with pushing margins (so-called giant condyloma of Buschke and Lowenstein) should be classified as verrucous carcinoma; this tumor shows aggressive local infiltration but does not metastasize. As all anal condylomata may harbor foci of high-grade dysplasia or invasive carcinoma, careful sectioning and complete histologic examination is required.

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“…On histopathology, p16 INK4a (mtm Laboratories, Heidelberg, Germany) immunostaining improves interobserver agreement 59,60 ; and its role in anal cytopathology is under investigation. 61 ProEx C reagent (BD, Franklin Lakes, NJ) and other molecular markers used to aid the diagnosis of cervical disease are also being investigated. 53 …”

Section: Histology Of Ain and Anal Cancermentioning

confidence: 99%

Anal cancer and cervical cancer screening: Key differences

Darragh

Winkler

2010

Cancer Cytopathology

193

203

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Cervical cancer and anal cancer share many similarities including causation by oncogenic human papillomaviruses; however, significant differences exist in their epidemiology, risk factors, biologic behavior, management, and treatment. Although rare, the incidence of anal cancer is alarmingly high and continues to increase in high-risk populations, particularly men who have sex with men regardless of their human immunodeficiency virus (HIV) status. There are no national screening guidelines for anal cancer. Using the success of cervical cancer screening as a model, anal cancer screening approaches apply anal cytology, highresolution anoscopy, and directed biopsy to guide treatment and management strategies. Although much has been learned about the natural history and epidemiology of anal intraepithelial neoplasia (AIN), the rate of progression of high-grade anal intraepithelial neoplasia (HGAIN) to invasive squamous cell carcinomas is not known. The impact of screening and treatment of HGAIN on morbidity and mortality from anal cancer are also unknown. Because the incidence of HGAIN and anal squamous cell carcinoma continue to increase, it is imperative to find pathways for effective screening, early detection, and therapeutic intervention. This article provides an overview of anal cancer screening while highlighting its differences from cervi- Compared with cervical cancer, anal cancer is rare. The National Cancer Institute estimates that 5260 patients will be diagnosed with anal cancer in 2010 and that 720 men and women will die of the disease. 1 Compare this to cervical cancer statistics in the United States for 2010: 12,200 will be diagnosed with cervical cancer and 4210 women will die and this is with successful opportunistic Papanicolaou (Pap) testing to screen for this cancer in the United States. Yet, in patients with the highest risk of anal cancer, its incidence was more than double that of cervical cancer prior to the initiation of Pap screening and is increasing, while rates for cervical cancer continue to decrease. As the incidence of anal carcinoma increases in populations at risk, cytologic screening, combined with early detection and treatment, has been proposed as a method to reduce the morbidity and mortality from invasive anal squamous cell carcinoma (ASCC).

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Immunoreactivity of p16 in anal cytology specimens

Cited by 18 publications

References 42 publications

Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

Diagnostic Problems in Anal Pathology

Anal cancer and cervical cancer screening: Key differences

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