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Squarzanti et al. J Cancer Metastasis Treat 2019;5:73 I http://dx.doi.org/10.20517/2394-4722.2019.19 Page 9 of 11

Although several questions are still open, soon further improvements might help to generate
microenvironments that also mimic the bacteria and virus migratory potential.

CONCLUsION
Overall this review highlights the importance of the in vitro 3D modeling research field for the study of
microbial induced epithelial carcinogenesis. Yet, further improvements are still needed to reach the level of
complexity of the real tissue. These models will hopefully help to better understand the respective roles of
virus and bacteria in HR-HPV-related cancers.

DeCLaRaTIONs
Acknowledgments
Authors thank Michelle Schoeman for the linguistic revision.

Authors’ contributions
Wrote part of the paper and prepared Table 1: Squarzanti DF
Wrote part of the paper and prepared Figure 1: Sorrentino R
Designed the review article and wrote part of the paper: Azzimonti B

Availability of data and materials
Not applicable.

Financial support and sponsorship
DFS was partially supported by BioLab Srl/Probiotical SpA.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

ReFeReNCes
1. Human papillomavirus and related diseases report. HPV Information Center. Available from: https://hpvcentre.net/statistics/reports/XWX.
pdf?t=1571975032537 [Last accessed on 25 Oct 2019]
2. Pouyanfard S, Müller M. Human papillomavirus first and second generation vaccines-current status and future directions. Biol Chem
2017;398:871-89.
3. Takes RP, Wierzbicka M, D’Souza G, Jackowska J, Silver CE, et al. HPV vaccination to prevent oropharyngeal carcinoma: what can be
learned from anogenital vaccination programs? Oral Oncol 2015;51:1057-60.
4. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for
Research on Cancer. 2018. Available from: https://gco.iarc.fr/today [Last accessed on 25 Oct 2019]
5. Squarzanti DF, Sorrentino R, Landini MM, Chiesa A, Pinato S, et al. Human papillomavirus type 16 E6 and E7 oncoproteins interact with
the nuclear p53-binding protein 1 in an in vitro reconstructed 3D epithelium: new insights for the virus-induced DNA damage response.
Virol J 2018;15:176.
6. Deschler DG, Richmon JD, Khariwala SS, Ferris RL, Wang MB. The “new” head and neck cancer patient-young, nonsmoker, nondrinker,
and HPV positive: evaluation. Otolaryngol Head Neck Surg 2014;151:375-80.
7. Sedghizadeh PP, Billington WD, Paxton D, Ebeed R, Mahabady S, et al. Is p16-positive oropharyngeal squamous cell carcinoma associated