Improve the nationwide cervical cancer screeningOur ambition is to improve the nationwide cervical cancer screening, with the possibility of using self sampling. Important herein is research on the use of new triage methods for hrHPV positive women, by using HPV genotyping or molecular biomarkers.
AimsStudies to the biological behavior of Human papillomaviruses (HPV) infected cervical lesions, identified multiple HPV genotypes in different biopsies of the uterine cervix of the same patient. Multiple HPV genotypes were detected in all patients with severe dysplasia, while only a single HPV genotype was detected in patients with invasive carcinoma. The distribution of single and multiple HPV genotypes within the cervix seems to depend on the stage of the disease.
The presence of multiple HPV genotypes within a single biopsy indicates that monoclonality may be a late event in carcinogenesis. The presence of multiple HPV types in a single patient indicates that a difference between HPV infections must exist to explain the oncogenic behavior of a specific virus strain. It is suggested that viral persistence and the viral load may play a role in this respect.
So when does an HPV infection become oncogenic? The presence of only HPV cannot be considered sufficient for oncogenesis; other risk factors must play an important role. Hard evidence is difficult to obtain to determine whether an HPV infection, or in fact, whether an HPV induced cervical lesion will regress or progress.
Among the possibilities available, we hypothesize that the viral persistence, viral load and genetic predisposition, are objective criteria which are possibly involved in the pathogenesis of cervical cancer development. There is sufficient reason to consider that either one of these aspects, or a combination of these, do determine the behavior of a cervical lesion or in the HPV integration event, as an important step to carcinogensis. Therefore current studies are directed to obtain insight into the regressive/progressive behavior of cervical lesions related to HPV infections.
DiscoveriesBoth epidemiological and molecular studies have now established that human papillomaviruses (HPVs) that development of human cervical carcinomas is causally associated with infection by HPV. The HPV family consist of many different types; over 90 have been identified to date, of which 30 genotypes can be found in the genital tract. HPV can be detected in up to 100% of cervical squamous cell carcinomas. Several HPV types, such as HPV types 16, and 18 have been implicated as sexually transmitted agents with an aetiological role in cervical carcinogenesis while other HPV types as HPV 6 and 11 are frequently detected in benign lesions such as condylomata acuminata. Therefore HPV 6 and 11 are called the benign or low-risk HPV types and HPV 16 and 18 are the malignant or high-risk HPV types. Women infected with the high-risk HPV types are considered to be at a higher risk for the development of cervical cancer than those who are not infected with HPV or who are infected with one of the low-risk HPV types.
BackgroundWorldwide 450,000 new cases of invasive cancer of the cervix are diagnosed every year. In developing countries, cancer of the cervix is the most frequent female malignancy and is responsible for about 24% of all cancers in women. Although screening programs, to identify precursor lesions of cervical cancer, have significantly reduced the mortality and morbidity of this disease, still more than 700 women have to be treated for cervical cancer in the Netherlands.
Human papillomaviruses (HPV) infections are prevalent in the general population. Obviously, not every women infected with a high-risk HPV type will develop cervical cancer. In fact, cervical cancer can be considered a very rare complication of a cervical infection with high-risk HPV. Clearly, additional virological, environmental, behavioral, immunological or ill-defined genetic factors must be implicated in the pathogenesis and progression of this cervical disease.
Related research groups
Research group Tumor targeting
William Leenders' group performs targeted quantitative next generation sequencing of RNA from surgery-derived cancer tissues in retrospective studies, tries to translate the findings into personalized precision therapy with available cancer treatments, and develops innovative targeted nanomedicines.read more