Evidence and impact of human papillomavirus latency

Abstract

At present, there is no consensus in the scientific community regarding the ability for human papillomavirus (HPV) infections to establish latency. Based on animal studies, a model of papillomavirus latency has been proposed in which papillomaviruses can be retained in the basal epithelial stem cell pool as latent infections and periodically induced to reactivate when the stem cell divides and one daughter cell is committed to terminal differentiation and induction of the viral life cycle. Tissue resident memory T-cells are hypothesized to control these periodic reactivation episodes and thus limit their duration. In this paper, evidence from human studies consistent with this model of papillomavirus latency is reviewed. Given the strong circumstantial evidence supporting a natural history of HPV infection which includes a immunologically controlled latent state, the longer term implications of HPV latency on a highly infected and aging population may warrant a more serious evaluation.

Keywords: HPV; Papillomavirus; cervical cancer.; latency; reactivation.

Fig. (1)

Illustration of misclassification of HPV infection status in studies with long interval sampling. Four hypothetical women are represented from onset of sexual debut (diamond) through their lifetime of type-specific HPV infection. All women acquire HPV soon after sexual debut. Woman #1 then clears infection sometime between t2-t3, woman #2 has infrequent recurrent detection throughout her life, woman #3 has infrequent reactivation then reactivation with longer duration at later life, and woman #4 has an increase in reactivation frequency (but not duration) in later life. If all women were enrolled at t1, woman 1 & 2 would have no recurrent detection observed, despite periodic recurrence in woman 2. Woman 3 &4 would be found to have a single recurrence at time 5, and the multiple recurrent detection which occurs during the sampling interval would be missed. If all women entered the study at t3, the recurrent events in women 3 & 4 would be misclassified as 'incident' because the past HPV infection was never observed under study follow-up.