The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer
Open accessAbstract
Infection by carcinogenic human papillomaviruses (HPV) results in precancers [cervical intraepithelial neoplasia (CIN)] and cancers near the ectoendocervical squamocolumnar (SC) junction of the cervix. However, the specific cells targeted by HPV have not been identified and the cellular origin of cervical cancer remains elusive. In this study, we uncovered a discrete population of SC junctional cells with unique morphology and gene-expression profile. We also demonstrated that the selected junctional biomarkers were expressed by a high percentage of high-grade CIN and cervical cancers associated with carcinogenic HPVs but rarely in ectocervical/transformation zone CINs or those associated with noncarcinogenic HPVs. That the original SC junction immunophenotype was not regenerated at new SC junctions following excision, not induced by expression of viral oncoproteins in foreskin keratinocytes, and not seen in HPV-related precursors of the vagina, vulva, and penis further support the notion that junctional cells are the source of cervical cancer. Taken together, our findings suggest that carcinogenic HPV-related CINs and cervical cancers are linked to a small, discrete cell population that localizes to the SC junction of the cervix, expresses a unique gene expression signature, and is not regenerated after excision. The findings in this study uncover a potential target for cervical cancer prevention, provide insight into the risk assessment of cervical lesions, and establish a model for elucidating the pathway to cervical cancer following carcinogenic HPV infection.
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Case–Control Study of Human Papillomavirus and Oropharyngeal Cancer
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Human Papillomavirus Infection as a Risk Factor for Squamous-Cell Carcinoma of the Head and Neck
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p63 Is Essential for the Proliferative Potential of Stem Cells in Stratified Epithelia
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“Immunohistochemistry, immunofluorescence, and Western blot analysis were performed as described previously and imaged at the Nikon Imaging Facility at the HarvardMedical School (17, 27).”
MethodSelf-citation2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests
Wright, T. C., Massad, L. S., Dunton, C. J., Spitzer, M., Wilkinson, E. J., & Solomon, D. (2007) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2007.07.047 · Cited by 841
Cited by
The Biology and Life-Cycle of Human Papillomaviruses
Doorbar, J., Quint, W., Banks, L., Bravo, I. G., Stoler, M., Broker, T. R., & Stanley, M. A. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.06.083 · Cited by 1,528
Carcinogenic human papillomavirus infection
Schiffman, M., Doorbar, J., Wentzensen, N., de Sanjosé, S., Fakhry, C., Monk, B. J., Stanley, M. A., & Franceschi, S. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.86 · Cited by 999
Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia
Egawa, N., Egawa, K., Griffin, H., & Doorbar, J. (2015) · Viruses · doi:10.3390/v7072802 · Cited by 553
Cervical Cancer Screening: Past, Present, and Future
Bedell, S. L., Goldstein, L. S., Goldstein, A. R., & Goldstein, A. T. (2020) · Sexual Medicine Reviews · doi:10.1016/j.sxmr.2019.09.005 · Cited by 500
Alemany, L., Saunier, M., Alvarado-Cabrero, I., Quirós, B., Salmeron, J., Shin, H.-R., Pirog, E. C., Guimerà, N., Hernandez-Suarez, G., Felix, A., et al. (2015) · International Journal of Cancer · doi:10.1002/ijc.28963 · Cited by 388
Metadata
- Authors
- Herfs, M., Yamamoto, Y., Laury, A., Wang, X., Nucci, M. R., McLaughlin-Drubin, M. E., Münger, K., Feldman, S., McKeon, F. D., Xian, W., & Crum, C. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2012-06-11
- Volume
- 109
- Issue
- 26
- Pages
- 10516-10521
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1973954265
- Cited by
- 437
- References
- 26
- FWCI
- 22.83
- Type
- journal article
- Language
- en
- Open access
- green
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- Herfs, M., Yamamoto, Y., Laury, A., Wang, X., Nucci, M. R., McLaughlin-Drubin, M. E., Münger, K., Feldman, S., McKeon, F. D., Xian, W., & Crum, C. P. (2012). A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1202684109
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
