The Host-Microbe Interplay in Human Papillomavirus-Induced Carcinogenesis

Abstract

Every year nearly half a million new cases of cervix cancer are diagnosed worldwide, making this malignancy the fourth commonest cancer in women. In 2018, more than 270,000 women died of cervix cancer globally with 85% of them being from developing countries. The majority of these cancers are caused by the infection with carcinogenic strains of human papillomavirus (HPV), which is also causally implicated in the development of other malignancies, including cancer of the anus, penis cancer and head and neck cancer. HPV is by far the most common sexually transmitted infection worldwide, however, most infected people do not develop cancer and do not even have a persistent infection. The development of highly effective HPV vaccines against most common high-risk HPV strains is a great medical achievement of the 21st century that could prevent up to 90% of cervix cancers. In this article, we review the current understanding of the balanced virus-host interaction that can lead to either virus elimination or the establishment of persistent infection and ultimately malignant transformation. We also highlight the influence of certain factors inherent to the host, including the immune status, genetic variants and the coexistence of other microbe infections and microbiome composition in the dynamic of HPV infection induced carcinogenesis.

Epstein–Barr Virus and Helicobacter Pylori Co-Infection in Non-Malignant Gastroduodenal Disorders

“…Clinical and epidemiological evidence supports the contribution of various viruses, including EBV, hepatitis virus, cytomegalovirus with gastritis and gastric cancer induced by H. pylori [67], and several studies have shown that gastric microbiota can regulate H. pylori infection and vice versa; this bacterium can modify the gastric microbiota composition [68][69][70]. On the other hand, the microbiota composition in several body niches exerts direct or indirect effects on virus infections, including EBV and human papilloma virus [71]. Therefore, testing potential crosstalk between EBV and H. pylori with gastric microbiota is an interesting line of investigation for further studies.…”

Microbiome factors in HPV-driven carcinogenesis and cancers

“…Furthermore, toll-like receptors (TLRs) act as a first-line of defense in recognizing viral infection and foreign bacteria. TLR9 has been suggested to recognize HPV infections and initiate an immune response, while E6 and E7 oncoproteins directly down-regulate TLR9 at a transcriptional level [19]. BV incidence has been associated with SNPs in TLR2/7, but their exact roles in BV are not well understood [20].…”

Human Papillomavirus (HPV69/HPV73) Coinfection associated with Simultaneous Squamous Cell Carcinoma of the Anus and Presumed Lung Metastasis

“…Human papillomaviruses (HPVs) represent a subset of papillomaviruses that are known to infect human hosts and to contribute toward carcinogenesis as etiologic drivers in a wide variety of cancers [1]. Virtually all cervical cancers are associated with high-risk human papillomavirus infections [1,2]. In addition, the landscape of HPV-related neoplasia continues to expand, including a spectrum of head and neck, anal, vulvar, penile, and vaginal carcinomas [3,4].…”

“…The risk for persistence of HPV infection appears to be influenced by both biological and environmental factors, including age, ability to mount an immune response, hormonal status, dietary habits, tobacco and alcohol usage, and coinfection with other sexually transmissible agents [5]. The specific HPV type involved in infection is also critical for prognosis because HPVs are highly tissue-tropic, with some high-risk types linked to persistent infection and induction of carcinogenesis [2][3][4].…”