Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the world.
HPV is the virus that causes genital warts. Though warts can cause a lot of distress, they are typically benign and not associated with serious long-term consequences. However, certain types of HPV are high-risk and cancer-causing. These oncogenic types are responsible for almost all cervical cancers in women, upwards of 80% of anal cancers in men and women, and are increasingly seen as a cause of head and neck cancers worldwide.
The incidence of anal cancer in the general population is roughly 2 per 100,000. In HIV-positive men who have sex with men (MSM), this number goes up to over 100 per 100,000. In fact, the rates of anal cancer in MSM surpass the rates of cervical cancer in women before the availability of routine cervical cytology (Pap smear) screening. However, because this is still a fledging research area, organized programs for anal cancer screening – particularly for HIV-positive MSM – are lacking.
Screening tests for anal HPV
Many of the methods used in anal cancer screening are taken directly from cervical cancer screening, given the similar pathogenesis and the fact that both develop within the same tissue types (squamous cells) in similar anatomic areas (squamocolumnar junction, or transformation zone).
Screening tests for anal HPV include anal cytology (Pap smear), along with high-resolution anoscopy with directed biopsies (analogous to colposcopy). Anoscopy is limited to specialized clinics, which exist only in large cities. In Canada, only five clinics exist – including one in Vancouver – with very limited capacity and often long wait times.
Role of anal cytology in predicting anal cancer precursors
The goal of anal cancer screening is to discover anal cancer precursors (also known as anal intraepithelial neoplasia [AIN]).
The first step in screening may involve an anal Pap smear. Similar to cervical cytology which examines squamous cells from the transformation zone of the cervix, this test involves swabbing the anal canal to examine squamous cells from the anal transformation zone. These cells are then examined for the presence of abnormalities.
The same system (Bethesda system) used to classify cervical cytology is used for anal cytology:
- low-grade squamous intraepithelial lesion (LSIL)
- high-grade squamous intraepithelial lesion (HSIL)
- atypical squamous cells of undetermined significance (ASCUS)
- atypical squamous cells – cannot exclude HSIL (ASC-H)
There are some potential issues with anal cytology. The performance characteristics are suboptimal, making it problematic as a standalone screening test. In a large study of HIV-positive MSM, the sensitivity of an HSIL Pap smear in predicting histologic, biopsy-proven high-grade disease (AIN-2 or -3) was very low (21%), with reasonable specificity (91%). Using ‘any abnormality’ as a threshold (ASCUS, LSIL or HSIL) yielded an improved sensitivity of 84%, but a specificity of 39%.
The clinical bottom line is:
- If you rely only on HSIL as your threshold, you will likely miss a significant number of high-grade lesions. On the flip side, if you rely on ‘any abnormality’ as your threshold, you may be over-investigating (and over-biopsying).
- There is currently very limited capacity to screen men for anal cancer in a widespread way, given the few clinics and the limited number of clinicians trained in these procedures.
- Though not particularly difficult, anal cytology requires specialized training, and this test is prone to yielding inadequate samples in inexperienced hands.
Though anal cancer is becoming increasingly recognized as an important, emerging health problem – particularly in HIV-positive MSM – there is not enough evidence yet to guide overall management, and limited practitioners and clinics to perform this screening work.
For now, the best tools widely available for anal cancer screening are clinical history and physical examination, including the digital ano-rectal exam (DARE), with referral to specialists/surgeons when needed, or to an anal cancer screening clinic if one is available in your area.
For more information on anal cancer, HPV and screening techniques, there is an excellent resource based out of Australia: http://www.thebottomline.org.au/