In the present study, we aimed to determine the HPV prevalence, distribution, and type concordance between cervical and oral samples of HIV+ women and HIV- matched controls in the southern region of Brazil, a geographic area with high incidence of HIV and CC. Our data demonstrated that HIV+ and HIV- women had a similar and high HPV prevalence in cervical and in oral sites. However, HIV+ women had higher prevalence of abnormal cytological findings compared to HIV- women. HPV type distribution was different between the anatomical sites within both groups, and HIV+ women commonly presented with narrower HPV types distribution, mainly in the oral mucosa. Finally, the frequency of concurrent HPV infection in both sites was low, and HPV type concordance was not observed.
Our results showed that the prevalence of cervical HPV infection was 44.3% in HIV+ women and 37.4% in HIV- women. Studies across different populations present varying prevalence of HPV infection, 45–97.1% in HIV+ women and 44.9–86.5% in HIV- women in the cervical site [20,24,25,33]. The high prevalence of HPV in HIV-negative women in this study can be explained, at least in part, because they were recruited from a Specialized Assistance Service (SAE) for sexually transmitted diseases and therefore are at higher risk for sexually transmitted infections including HPV. Additionally, the prevalence of oral HPV infection in HIV+ women and HIV- control were 14.8% and 9.4%, respectively. Other studies have shown that the prevalence of HPV infection in the oral site can vary significantly (12%–68.5% in HIV+ women and 2%–31.4% in HIV- women) [20,24,33].
Although the HIV infection was well controlled and cytology results showed absence of malignancy, abnormal cytological findings were significantly higher in HIV+ women than in HIV- women. These data are consistent with the results of the previous studies showing that HIV+ women are less likely to eliminate the virus with subsequent persistent hrHPV infection and have higher risk of developing precancerous lesion and malignancy, even with the appropriate use of antiretroviral therapy, than HIV- women [8,9,19,34,35].
Our results demonstrated no significant difference in HPV detection in the uterine cervix or oral mucosa between HIV+ women and HIV- women; however, HPV infection was significantly higher in the cervical mucosa than in the oral site in both groups. These findings are consistent with previous studies suggesting that the natural history of HPV infection varies by anatomical site and a higher prevalence of HPV infection is observed in the cervical mucosa than in the oral mucosa in HIV+ women [36–38]. This can be explained, at least in part, by the evidence that the oral cavity is a hostile environment for the establishment of infectious agents due to the presence of both mechanical and molecular mechanisms related to digestion [39]. More specifically, Fakhry et al. [39] conducted a study that directly compared the local immunologic profiles of the oral cavity and cervix from healthy women using paired secretion specimens. This study showed that the oral cavity contained significantly higher concentrations of immunoregulatory factors that were related to the adaptive and cell-mediated immune response compared to the cervix, which may in part explain the significantly lower burden of sexually transmitted infections such as Chlamydia trachomatis, HPV, and HIV-1 in the oral cavity than in the cervix. According to the authors, these findings provide additional information to better understand the differences in the etiology and natural history of pathogenic agents that are capable of colonizing both the oral cavity and female reproductive tract.
The most prevalent HPV types in cervical samples were hrHPV18 and hrHPV58 in both HIV+ and HIV- women; however, hrHPV45 and hrHPV16 were frequently detected in HIV+ women and HIV- women, respectively. Prevalence studies around the world have shown that the hrHPV types 16, 18, 31, 33, 35, 52, and 58 are the most commonly detected hrHPVs in CC, with hrHPV16 being the most common in all populations, with the exception of HIV+ people [1]. Data have consistently shown that HIV+ women are frequently more infected with other hrHPV types than hrHPV16 and hrHPV18, such as hrHPV52 and hrHPV58 [40]. The high prevalence of non-vaccine hrHPV types of 2-valent and 4-valent vaccines in the cervical and oral mucosa found in our study suggests that the 9-valent HPV vaccine is significantly required, which is considered important to reduce the risk of developing HPV-related cancers, specifically in the HIV+ population.
Unlike the distribution of HPV types in cervical samples, HPV type concordance between the HIV+ and HIV- groups in oral samples was not observed. hrHPV39 was the most common hrHPV detected in oral samples of HIV+ women, followed by hrHPV18, hrHPV45, hrHPV52, and hrHPV68, with these types being also frequently found in cervical samples in the same group. However, in HIV- women, the oral hrHPV types observed were totally different, with hrHPV51 and hrHPV66 being the most frequently detected hrHPV. Current evidence has shown that hrHPV16 and hrHPV18 contribute to the majority (approximately 85%) of HNC cases worldwide, while the remaining cancers are caused by hrHPV33, hrHPV35, hrHPV52, hrHPV45, hrHPV39, and hrHPV58 [41,42].
Examination of concurrent HPV infections in different anatomical sites has been limited. Hence, we concurrently investigated the prevalence of HPV infection and HPV type distribution in cervical and oral sites to better understand their clinical significance. The simultaneous HPV cervical and oral infection was low in both HIV+ and HIV- women. Moreover, HPV type concordance was not observed, a finding consistent with previous studies [20,24]. Taken together, these observations suggest a different predilection to different anatomical sites of various HPV types, and/or the ability of the two anatomical sites to clear certain HPV types or distinct exposures, while allowing for other HPV types to cause persistent oral and cervical HPV infections.
Prior investigations have demonstrated that engagement in some high risk behaviors may facilitate HPV infection and act as a cofactor to viral persistence, contributing to cancer progression in the oral and cervical mucosa. In the present study, we found that current smoking was associated in HIV+ women with overall and cervical HPV infection. Several studies have already demonstrated that smoking status acts as a predictor and co-factor in cervical HPV infection, which is possibly due to the alteration of the mucosa cells, making them more susceptible to infection, changing the immune mediators, causing DNA damage, and promoting the integration of HPV DNA into the host genome [42–45].