This study prospectively assessed the effects of hysterectomy on rates of HPV infection, using cervicovaginal lavage specimens from HIV-positive and HIV-negative women enrolled in a longitudinal cohort. HPV DNA was commonly detected after hysterectomy, suggesting that the vaginal epithelium is a common site of HPV infection. In addition, vaginal HPV prevalence was significantly greater in HIV-positive than in HIV-negative women, and positively associated with the level of HIV-related immunosuppression. There has been little previously reported regarding vaginal HPV infection in HIV-positive women, and these data provide novel evidence that host immunity plays an important role in control of vaginal HPV – findings consistent with reports that rates of vaginal cancer are increased in women with HIV/AIDS.19
Furthermore, hysterectomy was associated with a significant reduction in oncogenic but not nononcogenic HPV prevalence, consistent with recent reports suggesting that oncogenic HPV may have greater tropism for cervical than vaginal epithelium. The results were similar by HIV status, as well as similar in the two distinct study designs we used: (i) comparing women to themselves, before versus after hysterectomy (our primary analysis); and (ii) comparing women who had a hysterectomy before enrollment in the cohort to those without current hysterectomy but who later had the procedure. Both approaches helped address concerns regarding potential biases due to differences in the characteristics of women who do and do not undergo hysterectomy.
Interestingly, with increasing time from hysterectomy the prevalence of non-oncogenic HPV increased in both analyses, consistent with results of a prior study.4
Oncogenic HPV prevalence, in contrast, remained at a fairly stable but reduced level after hysterectomy. The incident detection of non-oncogenic HPV also increased with greater time since hysterectomy in our primary analysis, whereas the incident detection of oncogenic HPV decreased. One possible explanation why oncogenic HPV might have tropism for the cervix is the presence of the transformation zone, the narrow region where columnar cells of the endocervix meet the stratified squamous cells of the ectocervix. Indeed, as mentioned, one of the studies that motivated our investigation reported that greater cervical ectopy was associated with higher oncogenic HPV prevalence.5
However, why non-oncogenic HPV infection might increase following hysterectomy is unknown. It has been speculated that vaginal atrophy induced by oophorectomy (removal of the ovaries) may impair the integrity of vaginal tissue,4
increasing the risk of HPV infection with non-oncogenic types. If correct, though, oncogenic HPV infection would also be expected to increase over time, even if not to the same extent as with non-oncogenic HPV. Unfortunately, accurate data regarding oophorectomy were not obtained in the WIHS and, thus, could not be evaluated in this study. Nonetheless, given that similar results have been obtained in both of the studies in which hysterectomy has been evaluated, further research regarding these relationships is warranted, as it may inform our understanding of HPV viral-host interaction.
Vaginal SIL prevalence decreased after hysterectomy amongst HDFs; results that are in keeping with the decrease we observed in oncogenic HPV infection after hysterectomy, and not with the increase observed in non-oncogenic HPV infection. If correct, these data are consistent with a recent WIHS study that showed a stronger relation of vaginal cytologic abnormalities with oncogenic HPV than nononcogenic HPV (personal communications, L. Stewart Massad).
Several limitations to our study should be considered in interpreting the findings. In particular, the follow-up questionnaire did not ask the reason for hysterectomy in women who had their surgery during the study. Therefore, to minimize the possibility that our primary analyses might have been influenced by cases in which hysterectomy was conducted because of HPV-related disease we excluded women with evidence of high grade neoplasia at any time prior to hysterectomy. In addition, the number of women who underwent hysterectomy during WIHS follow-up was relatively small, leading to a modest sample size in this study.
It must be noted that hysterectomy should not be undertaken as a cancer prevention measure in the absence of other indications in women with HIV. Data from our study and others have shown that with regular screening and treatment for cervical neoplasia, the risk of cervical cancer, as well as the risk of vaginal cancer, is low in HIV-positive women.20-22
On the other hand, while HIV-negative women can stop Pap testing after hysterectomy in the absence of high-grade cervical neoplasia or cancer, it is unclear whether the risk of vaginal cancer is sufficiently low to allow HIV-positive women to stop Pap testing after hysterectomy.23
In summary, this study had three major findings, namely, that HPV infection of the vagina is common, that the rate of vaginal HPV infection is increased in immunosupressed HIV-positive women and, more speculatively, that oncogenic HPV may preferentially infect cervical compared with vaginal epithelium in both HIV-positive and HIV-negative women. Further research to better understand the biologic factors that underlie differences in HPV viral tropism may help to identify targets useful in chemoprevention.