Human Papillomavirus-Associated Cancers and the Potential Role of Local Bacterial Populations

Human papillomavirus (HPV) is the most common sexually transmitted infectious agent in the United States as well as globally. This review aims to examine neoplastic diseases associated with HPV with special emphasis on cancers of the uterine cervix and oropharynx. Among the group of high-risk HPVs, i.e., types of HPV that can cause abnormal cellular changes leading to malignancies, HPV genotypes 16 and 18 are commonly found in cervical cancer, whereas HPV-16 is the most detected HPV in oropharyngeal cancer. It is known that the HPV genome comprises three major functional regions: the early region, which encodes proteins such as E6 and E7; the long control region; and the late region, which encodes structural capsid proteins L1 and L2. The E6 and E7 proteins are pivotal to carcinogenesis. E6 promotes degradation of the tumor suppressor p53, while E7 inactivates the retinoblastoma protein, critically disrupting cell cycle regulation and enabling uncontrolled proliferation. These disruptions promote survival of HPV-infected cells–a requirement for the viral life cycle. The viral L1, the major capsid component, is used for classification, PCR detection, antigenic tests, and in prophylactic vaccine preparation. However, it is important to correlate the role of HPV with different risk factors, particularly when considering a wide variation in cervical cancer incidence rates in different nations and geographic regions. Compared to cervical cancer, HPV-positive oropharyngeal cancer risk factors are thought to be associated with sexual behavior primarily. Overall, the local microbial environment of both the cervicovaginal region and the oral cavity may play a significant role in cancer development. For example, an increase in certain bacteria has been documented in the course of disease, such as Fusobacterium in oropharyngeal cancer or Prevotella and Gardnerella in bacterial vaginosis. On the other hand, a depletion of beneficial bacteria in the cervicovaginal environment may contribute to the development of cervical neoplasia. In the case of cervical cancer, all risk factors possibly alter the cervicovaginal microbial flora adversely. The dominance of anaerobic bacteria could bring about pathological changes. In relation to the disease progression, an increasing level of Lactobacillus depletion has been reported. Similarly, in different head and neck cancers, investigators documented differences in bacterial genera between HPV-positive and HPV-negative cases. Furthermore, some investigators suggested that certain bacteria could serve as cancer biomarkers in oral regions. Various bacteria are present throughout the gastrointestinal tract, particularly in the large intestine (colon), where they form the largest populations, and they influence diverse pathophysiological processes both inside and outside the gut. The gut microbiota is a typical example of how alterations in it could be associated with pathological processes, including cancer development. Regarding their impact on other organs, different bidirectional communication networks have been proposed. One pertinent example is the gut–vaginal axis, which connects the microbial communities of these two organs. Currently, a growing number of studies are trying to manipulate this axis and reconstitute the cervicovaginal microbial flora in a favorable manner. Therefore, appropriate modifications of the local microbial environment could prevent pathological processes in an economical way.