A key finding in this and other studies is the higher incidence of HPV-associated anal cancer among women than among men.2,3,19
Risk factors for anal cancer among women include an increasing number of sexual partners, a history of anogenital warts, a previous history of cervical intraepithelial neoplasia of type 3 or of cervical cancer, a history of current smoking at the time of diagnosis, a history of anal intercourse, HIV-positive status, and immunosuppression. 8,20–27
HPV is known to be a necessary cause for 100% of cervical cancers,28
and HPV is the presumed shared etiologic agent that leads to the subsequent increased risk for anal cancer. Anal intercourse is among the presumed mechanisms by which HPV is introduced into the anal canal, although the percentage of women with anal HPV infections or with anal cancer who engage in anal intercourse has been found to be low in some studies.8,23
The low percentage may be because of underreporting of anal intercourse by study participants, or there may be other means by which HPV is introduced to the anal canal (ie, by the use of sex toys or auto inoculation via the fingers or vaginal discharge).8,29
Men share many of the same risk factors for anal cancer as women. In addition, MSM have been found to be at high risk for anal cancer.20,22,23
The incidence of anal cancer among MSM has been estimated to be 35 per 100,000.27
Men who practice receptive anal intercourse are generally at higher risk.20,22,23
Men with HIVare also at increased risk for anal cancer.27
To our knowledge, few studies to date have described the burden of anal cancer among racial and ethnic minorities in detail. In accord with our findings, Frisch and Goodman30
reported that Asians/Pacific Islanders had a significantly lower incidence of anal SCCs than did Hawaiian whites and US mainland whites. Cress and Holly11
also found that the incidence of anal SCCs was lower among Asians/Pacific Islanders than among other racial/ethnic groups in California. Asians/Pacific Islanders have a low incidence of HIV31
and sexually transmitted diseases (STDs) such as chlamydia and syphilis,32
as well as a lower prevalence of smoking than among other racial and ethnic groups.33
The lower incidence of STDs and the lower prevalence of these risk factors may contribute to the lower incidence of anal cancer in this population. The increased incidence of anal SCC after the age of 50 to 59 years among Asian/Pacific Islander women may be attributable to delayed onset of sexual activity and acquisition of HPV in this population or to viral latency.30
Hispanic men had a lower incidence of anal SCC than did non-Hispanic men, but a similar difference was not observed between Hispanic and non-Hispanic women. Cress and Holly also found that Hispanic women had a higher rate of anal cancer than Hispanic men, and that Hispanics overall had a lower incidence of anal cancer than whites and blacks. Overall, Hispanics have a lower incidence of STDs, such as chlamydia,32
and a lower prevalence of smoking than other racial/ethnic groups.33
However, both Hispanic men and women have a higher incidence of HIV than do whites. A lower percentage of Hispanic than non-Hispanic men report acquisition of HIV through male-to-male sexual contact, suggesting a lower prevalence of receptive anal intercourse in the Hispanic population, perhaps leading to a reduced risk of anal squamous cell carcinoma.34
Hispanic women have a higher incidence of cervical cancer in all age groups than do whites, blacks, and Asians/Pacific Islanders.35
Because a history of cervical cancer is a known risk factor for the later development of anal cancer, cervical cancer may have contributed to the higher incidence of anal cancer in Hispanic women aged >60 years in this study.6,7
We found that black men had a significantly higher incidence of anal SCC than did white men, and black women had a significantly lower incidence than did white women, similar to findings in other studies.2,3
The higher rate of SCC among black men was limited to black men aged <60 years, suggesting a cohort effect. Black men have the highest incidence of HIV/acquired immunodeficiency syndrome (AIDS) (124.8 per 100,000) compared with all other races/ethnicities, perhaps contributing to the higher incidence of anal cancer among younger age groups in this population. Interestingly, black women have a higher incidence of HIV/AIDS and STDs such as chlamydia and syphilis than white women.32,34
Although rates of anal cancer are currently lower among black women than among white women, we found that rates of anal cancer among black women have been increasing since 1973.
Previous trend analyses have noted that the incidence of invasive anal cancer increased from 1973 to 2000 in both men and women.2,3,19
This analysis shows that rates have continued to increase among men and women through 2004. Young (aged <50 years) and middle-aged women (ages 50–64 years) were found to have a significant increase in anal SCC rates from 1992 through 2004. Young (aged <50 years) and older (aged ≥65 years) men were found to have a significant increase in rates during the same time period. Black and white women and white men also had a significant increase in rates during the time period studied, in contrast to black men and Hispanics of both sexes. These differences may be attributable to differences in sexual behavior or other risk factors by age, sex, and race/ethnicity, and to MSM and HIV/AIDS in men.
A higher proportion of men and those aged <50 years were diagnosed with in situ anal SCC. This is consistent with findings from a previous study.2
Young men who have risk factors for anal cancer, such as HIV-positive status, may be under closer medical surveillance and may be screened for anal cancer, resulting in a higher proportion with in situ disease.36
A higher proportion of Asians/Pacific Islanders were diagnosed with regional and distant disease. The incidence of anal cancer among Asians/Pacific Islanders is low; therefore, the reduced index of suspicion in this population may result in a later stage at diagnosis.
Men had a lower 5-year relative survival than women for all stages of anal SCC. This observation may be associated with the higher mortality among men with HIV/AIDS37
or to premature death from heart disease and other causes. Blacks had lower 5-year survival rates than did whites for in situ, localized, and regional disease, perhaps because of the higher burden of HIV/AIDS in this population or differences in access to care.
The current analysis is limited by the absence of information regarding HPV status or indicators of HPV exposure, such as sexual orientation, HIV status, or exposure to STDs. Furthermore, cases of AIN III were excluded from the analysis because cancer registries were not required to submit these cases to the NPCR during the study period. Because some pathologists equate AIN III with in situ disease, the incidence of in situ anal carcinoma may have been underestimated. Other limitations include the small number of cases within some subgroups of interest and the wide confidence intervals. We were unable to examine trends for Asian and Hispanic subpopulations because both designations are comprised of persons from many different countries. Anal cancer incidence, survival, and risk factors for these groups are likely to vary considerably. Although the registry coverage for the South region was estimated to be 63% of the population, potentially biasing regional comparisons, the data covered 83% of the US, a substantial strength of this analysis.
The quadrivalent HPV vaccine is currently approved for use in young women. The vaccine provides coverage for HPV types 6, 11, 16, and 18. A bivalent vaccine, covering HPV-16 and HPV-18, may receive US Food and Drug Administration approval soon. Given that 85% of anal cancers are of a histology known to be associated with HPV, a substantial portion of all anal cancers are theoretically preventable with the HPV vaccine. Research is currently underway to determine the efficacy of the vaccine in men. Further studies regarding the safety and effectiveness of the vaccine in high-risk populations such as MSM and HIV-positive men and women are needed. Screening for anal cancer is not currently recommended by the United States Preventive Services Task Force. Some researchers have advocated screening for anal cancer through use of anal Papanicolaou (Pap) smears to detect AIN in high-risk populations, particularly HIV-positive men.38
To our knowledge, no randomized clinical trials currently exist that determine whether screening for anal cancer decreases mortality or improves outcomes.39
There is little information regarding the natural history of AIN and the effectiveness and tolerability of treatment for anal dysplasia.39
Further research is needed to determine the risks and benefits of screening for anal cancer, particularly in high-risk populations. Continued surveillance of anal cancers will also be necessary to determine the impact of the HPV vaccine on anal cancer incidence among women as use of the vaccine becomes widespread.