Revising ecological assumptions about Human papillomavirus interactions and type replacement

Abstract

The controversy over whether vaccine-targeted HPV types will be replaced by other oncogenic, non-vaccine-targeted types remains unresolved. This is in part because little is known about the ecology of HPV types. Patient data has been interpreted to suggest independence or facilitative interactions between types and therefore replacement is believed to be unlikely. With a novel mathematical model, we investigated which HPV type interactions and their immune responses gave qualitatively similar patterns frequently observed in patients. To assess the possibility of type replacement, vaccination was added to see if non-vaccine-targeted types increased their 'niche'. Our model predicts that independence and facilitation are not necessary for the coexistence of types inside hosts, especially given the patchy nature of HPV infection. In fact, independence and facilitation inadequately represented co-infected patients. We found that some form of competition is likely in natural co-infections. Hence, non-vaccine-targeted types that are not cross-reactive with the vaccine could spread to more patches and can increase their viral load in vaccinated hosts. The degree to which this happens will depend on replication and patch colonization rates. Our results suggest that independence between types could be a fallacy, and so without conclusively untangling HPV within-host ecology, type replacement remains theoretically viable. More ecological thinking is needed in future studies.

National- and state-level impact and cost-effectiveness of nonavalent HPV vaccination in the United States

“…We assumed no interactions among HPV types. Cohort studies have found some evidence of interactions among types for women with abnormal cytology but not for the general population (16,17), although models have shown that type interactions may exist in the general population at levels that are difficult to detect (18,19). However, type interactions and postvaccination type replacement is of less concern for the nonavalent vaccine that targets most oncogenic types than for the bivalent or quadrivalent vaccines (20).…”

Invasions of Host-Associated Microbiome Networks

“…In addition, spatial structure may also play an important role in structuring the microbial community within a given body-site. For example, patch dynamics are likely to affect the outcomes of human papillomavirus infections (Murall et al 2014) and possibly most skin or mucosal infections. Also, continuum models seem appropriate for sites containing biofilms, but there are few examples of this approach (though see D 'Acunto et al 2015).…”

Epithelial stratification shapes infection dynamics

“…In the case of patchy infections like HPV, a metapopulation modeling approach may be more appropriate (e.g. [24,60]) or a full spatial model [23]. We chose not to include space since much of the experimental data available on these systems is not spatial.…”

“…The vast majority of mathematical models of STI within-host dynamics focus on HIV (for a review, see [17]) but some investigate pathogens that only (or mainly) target epithelia such as Chlamydia [18][19][20][21][22], HPV [23][24][25][26], Epstein-Barr Virus (EBV) [27,28] or HSV [29]. A common feature of these models is that they focus on the pathogen and the associated immune response somehow at the expenses of the epithelium itself.…”

“…While both Chlamydia and HPV replicate intra-cellularly, these two infections exhibit contrasting strategies for infecting the squamous epithelium: HPVs cause non-lytic basal-up infections, whereas Chlamydia infections are from the surface-down and are lytic. As mentioned earlier, there are some previous mathematical models of both HPV and Chlamydia, which we can build on [18][19][20][21][22][23][24][25][26]. More importantly, the biology of these two pathogens are well studied, with their life-histories (HPVs [42] and Chlamydia [43]) well characterized, at least, more so than other epithelial infections.…”