Elsevier

Vaccine

Volume 24, Supplement 3, 21 August 2006, Pages S1-S10
Vaccine

Chapter 1: HPV in the etiology of human cancer

https://doi.org/10.1016/j.vaccine.2006.05.115Get rights and content

Abstract

The causal role of human papillomavirus (HPV) in all cancers of the uterine cervix has been firmly established biologically and epidemiologically. Most cancers of the vagina and anus are likewise caused by HPV, as are a fraction of cancers of the vulva, penis, and oropharynx. HPV-16 and -18 account for about 70% of cancers of the cervix, vagina, and anus and for about 30–40% of cancers of the vulva, penis, and oropharynx. Other cancers causally linked to HPV are non-melanoma skin cancer and cancer of the conjunctiva.

Although HPV is a necessary cause of cervical cancer, it is not a sufficient cause. Thus, other cofactors are necessary for progression from cervical HPV infection to cancer. Long-term use of hormonal contraceptives, high parity, tobacco smoking, and co-infection with HIV have been identified as established cofactors; co-infection with Chlamydia trachomatis (CT) and herpes simplex virus type-2 (HSV-2), immunosuppression, and certain dietary deficiencies are other probable cofactors. Genetic and immunological host factors and viral factors other than type, such as variants of type, viral load and viral integration, are likely to be important but have not been clearly identified.

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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