Chapter 1: HPV in the etiology of human cancer
Section snippets
Mechanisms of HPV carcinogenesis
Human papillomavirus particles consist of 8000 base-pair (bp) long circular DNA molecules wrapped into a protein shell that is composed of two molecules (L1 and L2). The genome has the coding capacity for these two proteins and at least six so-called early proteins (E1, E2, E4–E7) that are necessary for the replication of the viral DNA and for the assembly of newly produced virus particles within the infected cells. Both sets of genes are separated by an upstream regulatory region (URR) of
Case series
The largest series of cases of invasive cervical cancer investigated with a standard protocol has been assembled by the International Agency for Research on Cancer (IARC). About 1000 women with histologically verified invasive cervical cancer were recruited from 22 countries around the world. Frozen biopsies from the tumors were analyzed in a central laboratory for the detection of HPV-DNA, using strict control for the presence of malignant cells in sections adjacent to the sections used for
The role of HPV in anogenital cancers others than cervical cancer
The number of studies on the role of HPV in other genital cancers is limited, and in most, the search for HPV-DNA has been done for a few HPV types and in fixed tissue.
The available epidemiological studies indicate that cancers of the vagina and of the anus resemble cancer of the cervix with respect to the role of HPV. In both, HPV-DNA is detected in the great majority of tumors and their precursor lesions. Between 64 and 91% of vaginal cancers and 82 and 100% of VAIN-3 lesions are HPV-DNA
Evidence linking HPV to head and neck squamous-cell carcinoma (HNSCC)
Over the past 15 years evidence implicating HPV as an important carcinogenic agent in a subset of HNSCCs (cancers of the oral cavity, pharynx, and larynx) has been accumulating.
The most recent systematic review included 5,046 HNSCC specimens from 60 studies that employed PCR-based methods to detect and genotype HPV-DNA [20]. The estimated summary prevalence of HPV-DNA was 25.9%, although this was significantly higher in oropharyngeal SCCs (35.6%; range 11–100%) than in oral (23.5%; range 4–80%)
The role of cofactors in the etiology of cervical cancer
Although many women get cervical HPV infections, most do not progress to cervical cancer. A number of other cofactors are therefore likely to be involved in the disease process. Three groups of potential cofactors are: (1) environmental or exogenous cofactors, including hormonal contraceptives, tobacco smoking, parity, and co-infection with other sexually transmitted agents; (2) viral cofactors, such as infection by specific types, co-infection with other HPV types, HPV variants, viral load,
Disclosed potential conflicts of interest
NM: Steering Committee (Sanofi-Pasteur MSD).
XC: Consultant/Travel Grants (GlaxoSmithKline, Sanofi-Pasteur MSD); Research Grants (GlaxoSmithKline, Merck and Co., Inc.)
LG: Patents (Loyola University of Chicago, DFZ Heidelberg and licensed to GlaxoSmithKline and Merck and Co., Inc.)
Acknowledgements
We thank Mireia Diaz and Cristina Rajo for technical help with the figures, and Meritxell Nomen for secretarial assistance. This work was supported financially by the Fondo de Investigaciones Sanitarias, Spain [grant numbers FIS 01/1236, FIS 01/1237, FIS PI051308], the Instituto de Salud Carlos III Network, Spain [grant numbers RCESP C03/09 and RTICCC C03/10], the Ministerio de Educación, Cultura y Deporte, Spain [grant number SAB2000-0261]. None of the funding agencies had a role in the
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