Anal HPV Infection and Abnormal Cytology in HIV-infected Women

BACKROUND FOR THIS STUDY Anal cancer is a growing problem in the US. The incidence of anal
cancer has increased among both men (160%) and women (78%) from 1973 to 2000 in the US [1].
In HIV-infected men the incidence of SCCA (squamous cell cancer of the anus) was found to
range from 49-92 per 100,000 patient years [2]. This prompted recommendations on screening
for anal cancer in this population. HIV-infected women are also at increased risk for
developing anal cancer. A study based on data from AIDS and cancer registries found that the
risk of anal cancer among women in the general population is about 1.2% and it increases up
to 3.9% in the HIV-infected women. In addition, HIV-infected women had eight times the risk
of in situ anal cancer compared with the number of expected cases [3].

SCCA appears to have many similarities to cervical cancers. HPV has been detected in 88% of
anal cancer specimens with HPV-16 found in 73% of SCCA and HPV-18 in 7% [1]. In addition,
SCCA develops in the transformation zone between the squamous epithelium of the anus and the
columnar epithelium of the rectum, is frequently associated with dysplasia of the anus and
may be preceded by squamous intraepithelial changes which are also associated with HPV.

Cervical cytology, also known as pap smear, can detect cervical cancer and its precursors.
Countries who have adopted cervical cancer screening programs have had dramatic decreases in
both the morbidity and mortality rates of cervical cancer.

Anal cytology may also be used to screen for HPV associated anal lesions, and among
HIV-infected men who have sex with men, an abnormal cytology is frequently associated with a
dysplastic squamous cell lesion of the anus. Anal HPV infections (high risk types) have been
found in 53 ¿ 95% of HIV-infected men. Abnormal anal cytology has been found in 41-81% of
HIV-infected men screened with high-grade cytologic findings in 2-25% of these patients [2].

There have been only a few studies looking at anal cytology in HIV-infected women. The
largest study (n=235), by Holly and Palefsky [4], found that HIV positive women had a 26%
prevalence of anal cytologic abnormalities (mostly atypical squamous cells of undetermined
significance [ASCUS] and low grade squamous intraepithelial lesions [LSIL]). Forty-six of
these women with abnormal cytology (60) underwent high resolution anoscopy (HRA) and 14 were
found to have biopsy proven HSIL.

Several risk factors for anal cytologic abnormalities in women have been suggested, such as
positive anal HPV test, history of anal intercourse, history of cervical squamous
intraepithelial lesions (SIL), history of vulvar warts, multifocal cervical SIL, history of
sexually transmitted infections, more than 10 sexual partners, history of cervical, vulvar
or vaginal cancer, immunosuppression after solid organ transplantation, HIV infection,
long-term corticosteroids use and cigarette smoking.

It has been suggested that all HIV-infected women, women with cervical cancer and women with
high-grade vulvar disease or cancer should be screened for anal cytologic abnormalities.
However, as described above there is very scanty literature describing the prevalence and
incidence in this patient population and the largest study was conducted prior to the HAART
era.

We plan to estimate the prevalence and 6-12 month incidence of abnormal anal cytology with
histologic correlates in the HIV-infected women seen at BMC. We hope that the information
will allow us to make screening recommendations for this patient population.

Inclusion Criteria:

- Age 18-64 years

- HIV infected women

- due for cervical cytologic screening

Exclusion Criteria:

- Pregnancy

- On chronic anticoagulation medication

- Life expectancy of the woman is less than 1 year

- If the woman has had a cervical or anal pap test in the last 6 months