HPV

How Does Human Papillomavirus (HPV) Infection Drive the Progression of Cervical Cancer?

Posted on by Ken Doyle

Cervical cancer is a major health problem for women, and it is currently the fourth most common cancer in women globally (1). A worldwide analysis of cancer estimates from the Global Cancer Observatory 2018 database showed that cervical cancer disproportionally affects lower-resource countries, on the basis of their Human Development Index; it was the leading cause of cancer-related death in women in many African countries (1).

Global cervical cancer incidence 2018
Estimated cervical cancer global incidence rates from the GLOBOCAN 2018 database; image generated using IARC (http://go.iarc.fr/today).

Infection by human papillomavirus (HPV), a double-stranded DNA virus, is the leading cause of cervical cancer. Many types of HPV have been identified, and at least 14 high-risk HPV types are cancer-causing, according to a World Health Organization (WHO) fact sheet. Of these types, HPV-16 and HPV-18 are responsible for 70% of cervical cancers and pre-cancerous cervical lesions. HPV infection is sexually transmitted, most commonly by skin-to-skin genital contact. Although the majority of HPV infections are benign and resolve within a year or two, persistent infection in women, together with other risk factors, can lead to the development of cervical cancer [reviewed in (2)].

Continue reading “How Does Human Papillomavirus (HPV) Infection Drive the Progression of Cervical Cancer?”

Cell Free Expression Application: In vitro degradation assay

Posted on by Gary Kobs

A protein chain being produced from a ribosome.
A protein chain being produced from a ribosome.

Researchers and clinicians are fairly certain that all cervical cancers are caused by Human Papillomavirus (HPV) infections, and that HPV16 and HPV18 are responsible for about 70% of all cases. HPV16 and HPV18 have also been shown to cause almost half the vaginal, vulvar, and penile cancers, while about 85% of anal cancers are also caused by HPV16.

E6 is a potent oncogene of HR-HPVs, and its role in progression to malignancy continues to be explored. The E6 oncoprotein of HPV can promote viral DNA replication through several pathways. It forms a complex with human E3-ubiquitin ligase E6-associated protein (E6AP), which can in turn target the p53 tumor-suppressor protein, leading to its ubiquitin-mediated degradation. In particular, E6 from HR-HPVs can block apoptosis, activate telomerase, disrupt cell adhesion, polarity and epithelial differentiation, alter transcription and G-protein signaling, and reduce immune recognition of HPV-infected cells.

In a recent publication a new procedure generated a stable, unmutated HPV16 E6 protein (1). Continue reading “Cell Free Expression Application: In vitro degradation assay”