The primary aims of this study were to examine the prevalence of HPV infection and the distribution of HPV genotypes, as well as the potential benefit of HPV vaccination, in two distinct South Dakota populations. We found that the prevalence of HPV infection among AI women was more than twice that of White women in our samples. Because we are extremely confident that none of the study participants had prior Gardasil vaccination, these differences cannot be attributed, even in part, to discrepancies in vaccine administration or uptake. Increasing age was negatively correlated with HPV infection among AI women, whereas no such trend was detected among the White sample. These findings suggest that efforts to prevent HPV infection must be tailored to the disease burden, the specific HPV prevalence patterns, and the educational and social background of the target community.
We previously reported that 22% of AI women in a Northern Plains service unit had HPV infections, a prevalence considerably higher than the 7% observed among AI women in New Mexico  and comparable to the 21% documented for Alaska Native women . In a recent study of a large and diverse population of U.S. women, Datta and colleagues reported the prevalence of high-risk HPV infection among AI and Alaska Native women as 25% . High-risk types were determined by the Hybrid Capture 2 assay (Digene, Gaithersburg, MD), which returns a positive result in the presence of any of 13 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 68). Unlike the present study, however, Datta and colleagues did not identify individual HPV types, and their sample included fewer than 180 AI women recruited nationwide.
The disparity in HPV prevalence between AI and White women residing in the Northern Plains may contribute to the disproportionately high rate of cervical cancer in the AI population. The Northern Plains incidence rate for cervical cancer in AI women is 11.3 per 100,000, which is 1.5 times higher than in non-Hispanic White women (7.5 per 100,000). Recent publications have documented an incidence of cervical cancer among AI women in South Dakota as high as 16.2/100,000, compared to 6.1/100,000 among non-Hispanic White women , and an age-adjusted cervical cancer mortality in the Dakotas nearly twice the national average (4.5 per 100,000 vs. 2.7 per 100,000) .
We also observed different patterns of HPV infection in our two study populations. Overall, AI women showed more variation in prevalent HPV types, and significantly more AI women were infected by HPV types that would not have been prevented by current HPV vaccines. Previous genotyping studies conducted in predominantly White populations have documented that HPV-16 and HPV-18 are implicated in up to 70% of cervical cancer cases in the U.S and worldwide [32, 33], but virtually no AI women participated in these studies. Although vaccination is still in order, our results suggest that the protective benefit conferred by current HPV vaccines might be less for some AI women than for their White counterparts. Of note, recent evidence suggests that despite receiving HPV vaccination, some women still develop cervical cancer, likely unrelated to HPV-16 or HPV-18 . Among AI women in the present study, the diversity of oncogenic types that are not preventable by existing vaccines might further contribute to the high rates of cervical cancer previously observed among AI women in the Northern Plains.
Our findings have substantial relevance to public health efforts aimed at improving cervical cancer screening among AI women. The "All Women Count" cancer screening program funded by the State of South Dakota covers Pap testing for eligible women under the age of 30, but likely misses many women with HPV and cervical dysplasia . Notably, the National Breast and Cervical Cancer Early Detection Program found that AI women more often reported never having a Pap test than their non-AI counterparts, and also had the highest proportion (4.4%) of abnormal Pap tests . Although our findings need to be replicated in other AI communities, they raise the question of whether the Indian Health Service might consider universal HPV screening for selected service units.
This study is limited in several ways. First, because the study population was a convenience sample drawn from the local service units, our findings may not be pertinent to all AI women living in the Northern Plains of the U.S., and cannot be generalized to other rural or urban populations. Nevertheless, we had an exceptionally high participation rate, and we believe that our samples are an accurate representation of the patient populations, both AI and White, at all clinic sites. Of note, we have additional, unpublished results from 212 AI women living in Montana (ages 16-65), suggesting an HPV prevalence of 37%, very similar to the 42% prevalence observed in our sample of AIs living in South Dakota.
Second, our sample size was relatively small compared to many studies of HPV prevalence. Even so, this is the first study to examine HPV prevalence patterns in a high-risk AI population with a geographically localized White comparison group, and despite the small sample size, we were able to detect statistically significant differences between the groups, with important clinical and public health implications.
Third, we cannot disentangle the effects of urban residence from race. However, very few White women live on reservations, and only a negligible proportion of AI women were evaluated in the regionally-matched urban clinic, making the selection of samples evenly distributed between race and region virtually impossible.
Fourth, we did not use prior receipt of Gardasil vaccination as an exclusion criterion. Nevertheless, we are confident that our results remain unaffected by this limitation, since data on all White women and many AI women were collected before vaccine approval. Further, the AI women who were sampled in 2007-2008 were older than the target age range for HPV vaccination and had no insurance coverage from the Indian Health Service for this purpose. Even in the unlikely event that a few AI participants had prior vaccination, we would expect any resulting bias to be in the direction of less prevalent infection in this group.
Fifth, the absence of HPV vaccination among study participants prevented us from considering population differences in vaccine uptake; future research should examine this phenomenon more closely in minority communities.
Finally, we did not consider the additional prevention of HPV-31 provided by the Cervarix vaccine. Nevertheless, only four AI women, and no White women, were infected by HPV-31, so the inclusion of Cervarix in this analysis would have added confusion without altering our conclusions.