The carcinomas in males. Anal intraepithelial neoplasia (AIN),

The Human Papillomavirus
(HPV) is the most common sexually transmitted infection (STI) in the world and is
an identifiable source of 93% of anal carcinomas and 90% of anal condylomata
acuminata (The HPV and Anal Cancer Foundation, 2017).  Due to the asymptomatic nature of the virus,
the prevalence rate of HPV is difficult to determine. However, a 50% to 80%
lifetime exposure and infection rate worldwide has been reported (Hathaway,
2012). Within the United States alone, 80 million individuals are infected with
HPV with an estimated 14 million newly diagnosed HPV infections annually (The
HPV and Anal Cancer Foundation, 2017).

Research has indicated that much
like cervical carcinoma, there is a strong association between anal carcinoma
and HPV (Crawshaw et al., 2015). Based on the United States cancer registries
from 2008-2010, Saraiya et al. (2015) indicated an estimated 1,916 HPV-associated
anal carcinomas in males. Anal intraepithelial neoplasia (AIN), an HPV-related
dysplastic change in the cells of the anal canal, is a known precursor to anal
carcinomas and may be classified as low-grade (AIN I) or high-grade (AIN II and
AIN III) dysplasia based on its ability to produce neoplastic transformation (Crawshaw
et al., 2015; Dietrich et al., 2015). Low-grade AIN is associated with anal
condylomata acuminata and therefore, is not considered a direct precursor to
anal carcinoma. However, high-grade AIN is considered a pre-cancerous lesion
and may result in anal carcinoma following chronic infection with high-risk HPV
strains (Dietrich et al., 2015).

Although anal
carcinoma is relatively rare, rates have increased steadily over the decades (Shiels,
Kreimer, Coghill, Darragh, and Devesa, 2015). Within
the general population, the estimated incidence of anal carcinoma is
approximately one per 100,000 (Salit et al, 2010). The rates are more frequent
in HIV-positive MSM, with a reported incidence of 60-160 per 100,000 and are
comparable to rates of cervical carcinoma in females prior to the advent of
cervical pap screening (Salit et al., 2010). Dietrich et al. (2015) reported a
higher prevalence rate of anal HPV infection (>90%) and AIN (>70%) in MSM,
as well as an 80 to 100-fold increase in anal carcinoma risk in this select
population. Machalek et
al.
(2012) reported that based on systematic reviews and meta-analysis, the
prevalence of high-grade AIN was 29.1% in HIV-positive men who have sex with
men (MSM) with an incidence ranging from 8.5 to 15.4% annually. Furthermore,
the progression from a high-grade AIN to anal carcinoma has been reported to
develop significantly faster in HIV-positive patients than in the general
population (Dietrich et al., 2015).

HIV-positive
patients have increased prevalence and may exhibit a more aggressive course of HPV-disease
progression. This may be a result of direct interactions between HIV and HPV as
well as the presence of an attenuated immune response and chromosomal
instability (Nahas et al, 2009). The use of combination antiviral therapy has
reduced HIV-related opportunistic infections and mortality (Salit et al.,
2010). Due
to antiretroviral management, HIV patients have prolonged survival and there is
suggestion that because of this prolonged survival, increasing rates of anal
carcinoma may be realized (Nahas et al., 2009).

As a result of this known
association between HPV, AIN, and anal carcinoma, there has been a growing
concern that a screening protocol be established for high-risk populations such
as HIV positive individuals (Crawshaw et al., 2015). Considering the decrease
in cervical carcinomas since the advent of cervical pap testing, the use of
anal pap cytology has been accepted as a screening method for AIN (Crawshaw et
al., 2015).  The terminology and grading
criteria for anal pap cytology is equivalent to that of cervical squamous
intraepithelial lesions, which makes use of the Bethesda classification system.
This system differentiates between normal cytology, atypical squamous cells of undetermined
significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL),
high-grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma
(Dietrich et al., 2015).  While cervical pap
cytology exhibits satisfactory sensitivity and specificity, the reported
overall sensitivity and specificity of anal pap cytology is variable with a
reported range from 69% to 93% and 32% to 59% respectively (Leeds & Fang,
2016).  Leeds and Fang (2016) reported
anal cytology specificity for diagnosing the correct degree of dysplasia was
poor with routine reports of low-grade dysplasia for lesions that were found to
be high-grade dysplasia upon histopathology. Furthermore, the authors indicated
that the sensitivity of anal pap cytology is decreased in high-risk groups and
false-negative cytology has been reported as high as 23% in MSM and 45% in
HIV-positive individuals. Therefore, the aim of this pilot
study was to determine the correlation between anal pap cytology and tissue
histology in HIV-positive males diagnosed with AIN.

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