In the natural history of HPV infections, HPV virions can induce two different pathways, namely the infectious virion producing pathway and the clonal transforming pathway. An overview is given of the burden that is associated with HPV infections that both lead to cervical cancer and temporal subfertility. That HPV infections cause serious global health burden due to HPV-associated cancers is common knowledge, but that it is also responsible for a substantial part of idiopathic subfertility is greatly underestimated. The bulk of the detected HPV DNA whether in men or women is however infectious from origin. Because the dissociation between HPV viruses and HPV virions or infection and disease remains difficult for clinicians as well as for HPV detection, we propose a review of the different effects caused by the two different HPV virion induced pathways, and highlight the mechanisms that are responsible for causing transient subfertility and cancer.
When reviewing the evidence it seems evident that determining the origin of the detected HPV DNA is the key to predict the impact of the HPV infection.
When the detected viral HPV DNA originates from a dividing cell, the detected HPV DNA is never infectious (dividing cells do not support virion production) and does not affect fertility, but the viral DNA can transform the dividing cell it resides in, which could in time lead to pre-cancer and cancer. High-risk HPV oncogenic proteins can transform dividing cells or lead to blocking of the cell division of the early embryo. It always leads to a self-limiting HPV infection since no progeny virions can be made and the HPV life cycle ends.
Viral HPV DNA originating from non-dividing differentiated cells or from free virions, is infectious and exerts its deleterious effects thru weakening or incapacitating the cells it resides in. For the already dying epithelial cells the new virions are released when the cells desquamate and allow to restart the HPV life cycle. In embryos the accumulation of newly formed virions in the syncytiotrophoblasts results in the weakening of the implantation bond with the endometrium and diminished energy uptake leads to miscarriage. For spermatozoa the binding or internalization of viral DNA also leads to a decrease in functionality of sperm.
Independent of the number of HPV types detected, serial measurement of type specific viral load allows to identify the origin of the detected HPV DNA and makes it possible to assess the impact of the HPV infection for cancer screening or fertility.
Although HPV is not a lytic virus, harboring its DNA will ultimately lead to cell death or immortality depending on the cell type.
Human Papillomavirus (HPV) virion induced cancer and subfertility, two sides of the same coin. Depuydt CE, Beert J, Bosmans E, Salembier G. Facts Views Vis Obgyn. 2016 Dec;8(4):211-222. Review.