In the present study, we aimed to determine the HPV prevalence, distribution, and type concordance between cervical and oropharyngeal 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 + women had a higher HPV prevalence in cervical and in oropharyngeal sites than HIV- women. Additionally, 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 oropharyngeal mucosa. Finally, the frequency of concurrent HPV infection in both sites was low, and HPV type concordance was not observed.
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. Additionally, our results showed that the prevalence of HPV infection in cervical and oropharyngeal mucosa was higher in HIV + women (48.7%) than in HIV- women (41%). The prevalence of cervical HPV infection was 44.3% in HIV + women and 37.4% in HIV- women. Studies across different populations showed varying prevalenceof HPV infection, that is, 45–97.1% in HIV + women and 44.9–86.5% in HIV- women in the cervical site [20, 24, 25, 33]. However, the prevalence of oropharyngeal 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 oropharyngeal site can vary significantly (12–68.5% in HIV + women and 2–31.4% in HIV- women) [20, 24, 33]. These results suggest that the prevalence of cervical and oropharyngeal HPV infection may vary widely according to the anatomical sites, study population, geographical region, and detection methods applied, but oropharyngeal HPV infection seems to be less common irrespective of the population group studied.
Regardless if HAART is appropriately used and HIV infection was well controlled, the prevalence of HPV infection was higher in the HIV + group than in the HIV- group in both anatomical sites. Furthermore, the HIV + group presented with substantially more abnormal cytological findings in cervical samples compared to the HIV- group. These data are consistent with the results of the previous studies showing that HIV + women have higher prevalence and incidence of HPV infections in all anatomical sites and 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 oropharyngeal mucosa between HIV + women and HIV- women; however, HPV infection was significantly higher in the cervical mucosa than in the oropharyngeal site in both groups. These findings are consistent with the findings of 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 oropharyngeal 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.
HPV types that were most prevalent 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 + populations [1]. Data have consistently shown that HIV + women are frequently more infected with types of hrHPV other than hrHPV16 and hrHPV18, such as hrHPV52 and hrHPV58 [40]. The high prevalence of non-vaccine oncogenic HPV types in the cervical and oropharyngeal 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 oropharyngeal samples was not observed. hrHPV39 was the most common hrHPV detected in oropharyngeal 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 oropharyngeal hrHPV types observed were totally different, with hrHPV51 and hrHPV66 being the most frequently detected hrHPVs. 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 oropharyngeal sites to better understand their clinical significance. The simultaneous HPV cervical and oropharyngeal infection was low in both HIV + and HIV- women. Moreover, HPV type concordance was not observed, a finding consistent with that of the 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 oropharyngeal 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 with cervical and oropharyngeal HPV infection. Several studies have already demonstrated that smoking status acts as a predictor and co-factor in 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].