We have demonstrated an ability to institute an anal cancer screening program as part of routine HIV care in an ethnically diverse inner city setting. During the study period we screened approximately half (49%) of the clinic population that was seen for HIV care. This included screening a substantial number (32%) of women. Although current recommendations for anal cancer screening are specifically targeted toward MSM, high-grade anal dysplasia has been demonstrated in 36% of intravenous drug users who have no history of receptive anal intercourse.15 In our study we found that 22% of patients with intravenous drug use and 35% of patients with heterosexual sex as their only recorded HIV risk factor had abnormal anal cytology. This increased rate among heterosexual men and women is consistent with other published studies.14,25–27 The proportion of abnormal anal cytologies we found in men reporting having MSM as their HIV risk factor (39%) was lower than reported in other studies, which were concentrated in high-risk MSM communities.28 However, the risk factors in our study were collected retrospectively and were based on coding by providers in clinic charts. Thus, we may have underestimated the number of patients who have receptive anal intercourse. Nevertheless, our experience is more typical of a “real-world setting” in which providers often do not routinely collect an in-depth sexual history.29,30
We found that patients with an abnormal anal cytology were more likely to have anal disease on perianal visual inspection compared to those with a normal anal cytology. In the multivariate analysis, anal disease was associated with increased odds of having an abnormal anal cytology. However, only 30% of those with an abnormal anal cytology had anal disease on physical exam. The majority (70%) of patients with abnormal anal cytology findings did not have anal disease at the time of their anal cytology. In addition, 17 (9%) patients with a normal anal cytology had anal disease. One explanation for this finding is that only the perianal area is visible on examination, whereas the anal cytology samples were from within the anal canal, where anal dysplasia may occur.
The patients with an abnormal anal cytology were also more likely to have a lower CD4+ T-cell nadir and lower CD4+ T-cell count at the time of the anal cytology compared to those with a normal anal cytology. Interestingly, these patients were more likely to be on ART. This may reflect the treatment of patients' more advanced HIV disease. Although there is controversy regarding anal carcinoma's responsiveness to HAART, HAART does not appear to have an impact on anal HPV infection.15,31,32 HIV has a local immunosuppressive effect in the anal mucosa that is not responsive to HAART even with increases in systemic CD4+ T-cell counts and decrease in HIV viral load.8,33,34 This continued local immune suppression may be the mechanism via which HPV leads to anal carcinoma, as the decreased immune surveillance by dendritic cells allows transformed cells to grow unchecked.35
It has been shown previously that women with a history of cervical dysplasia are at increased risk for developing anal dysplasia. We were not able to demonstrate this in our study, but this may be because cervical Papanicolaou smear or colposcopy results were not always available. Many of the women received gynecological care at another institution and records were not available for review.
Of the 74 patients who were identified with cytologic evidence of anal dysplasia, only 27 received high-resolution anoscopy. Only 9 patients with visible lesions on anoscopy had a biopsy. This highlights many of the barriers to incorporating a cancer screening program into routine clinical care including substantial physician training and resources for anoscopy-related activities.36 The anal cytology was accepted by the patients and patients did not complain of side effects from this screening test. Yet, it was much more difficult to insure adherence with surgical anoscopy and biopsy follow-up. Barriers to surgical evaluation included patient-centered difficulties such as the perceived intolerability of the anoscopy procedure, fear of a cancer diagnosis, and difficulties with maintaining clinic appointments. Furthermore, as patients were initially referred for a surgical evaluation, there was confusion about the need and type of evaluation these patients required. Some patients were receiving high-resolution anoscopy and acetowhitening with biopsy of dysplasic lesions, while others received an anal examination or repeat anal cytology. With ongoing education to our surgical residents and scheduling the anal dysplasia follow-ups to 1 clinic day a week (2 clinic attendings), we were able to overcome this barrier.18,24,37 Lastly, even though the anal cytology was well accepted by patients, only half the patients seen were actually screened. This is at least partly due to the complexity and advanced HIV disease stage of our patients. If other more urgent medical problems were apparent, these would take priority and management of their anal disease would become a secondary or unaddressed issue. Despite these barriers, during the course of the screening program, 2 patients (0.7%) were identified with SCCIS. These 2 patients have been successfully treated with local therapy. They are currently being followed and remain disease free.
Our data does not show consistency between cytology and histology findings. The 3 patients with HSIL on cytology had no lesions seen on anoscopies and the 2 patients with SCCIS on biopsy had ASCUS and LSIL on cytology. This finding is consistent with other published reports.18,38 Palefsky et al. have shown that anal cytology screening in homosexual and bisexual men has a positive predictive value of 38% and negative predictive value of 84% when ASCUS was included as abnormal, as was done in with our study.18 The positive predictive value of the examination was driven by the higher disease prevalence in this patient population. In our study, only 38% of patients self-identified as having MSM as their HIV risk factor so the positive predictive value of the anal cytology screening program would likely be lower. Given that all the patients with high-grade lesions on histology were patients with ASCUS or LSIL, this study supports the recommendation of surgical evaluation of any patient with abnormalities, including ASCUS. One limitation is that approximately 32% of the patients with abnormal cytology did not receive anoscopy with biopsy. The majority of patients who did not receive an anoscopy were those with low-grade cytologic lesions.
In summary, we were able to incorporate anal cancer screening as part of routine HIV care in an urban HIV clinic setting with diverse HIV risk factors. We found cytologic abnormalities in patients without obvious risk factors, suggesting that anal cancer screening should be performed on all HIV-infected patients regardless of HIV risk factors and gender. The follow-up for abnormal anal cytology represents the most difficult aspect of the screening program. Our experience demonstrates some of the “real world” problems with setting up any screening program. It was difficult to get some patients to schedule or arrive for anoscopy even though they were aware of their abnormal anal cytology results. It then took several months to develop a uniform surgical evaluation for follow up of this new screening test. The estimated burden of disease is ∼146,372 men and ∼18,686 women and any widespread screening program would require substantial additional physician resources and training.36 Even in a group of physicians who are motivated to do such a screening program, there are difficulties and time involved in ensuring that everyone is appropriately trained. Any future recommendation for routine anal cancer screening for HIV-infected patients will have to take into consideration these implementation difficulties.
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