a retrospective longitudinal clinical cohort study to investigate HPV testing post-treatment and the risk of recurrence of (cervical) disease on the long term.

In the Netherlands, each year over 5000 women are treated for a high-grade
premalignant cervical lesion (Cervical Intraepithelial Neoplasia * CIN). Since
a persistent infection with the human papillomavirus (HPV) is the key causative
agent in the carcinogenesis, the presence of this virus can be demonstrated by
a HPV test (GP5+/6+ PCR enzyme immuno assay). Despite treatment, the overall
prevalence for recurrent disease is stated between 5 and 30 percent, with the
majority occurring in the first two years after initial treatment. Even after
20 years however, the risk to develop a recurrent lesion is still significantly
increased. Furthermore, women who have been treated for prior cervical cancer
have a high relative, although low absolute, risk of being diagnosed with anal
and/ or vaginal cancer.
If the hrHPV is cleared after treatment, this has a negative predictive value
of almost 100 percent. However, hrHPV persistence is highly associated with the
recurrence of a premalignant lesion within two years. Only few studies have
investigated the predictive value of the hrHPV test on the development of
premalignant genital lesions on the long term. More insight into this relation
may lead to more efficient strategies to identify the women at risk for
recurrent high-grade (cervical) disease.

The primary objective is to determine the positive and negative predictive
value of an hrHPV test after treatment for the development of recurrent
(cervical) disease on the long term.

The study is designed as a retrospective longitudinal clinical cohort study in
which we investigate the chance of the development of recurrent disease on the
long term of the cohorts described in Study Population.
All these women will be contacted to give a brief overview of the study and to
ask in they want to receive information over our new study. If so, a PIF will
be send. After approximately two weeks an appointment at the research
consulting hour at the outpatient clinic of one of the participating hospitals;
the VU University Medical Center in Amsterdam, the Erasmus University Medical
Center in Rotterdam or the Reinier de Graaf hospital in Voorburg, is made for
subjects who are willing to participate.
In general, the subject will visit the outpatient clinic only once. In this
visit the following acts will be performed:
- Check inclusion and exclusion criteria.
- Obtain written informed consent and assign study number
- Collect gynaecological history, and complete behavioral questionnaire
- Collect a cervical (vaginal) sample for hrHPV testing as well as for
cytological evaluation.
- Make an appointment to discuss the test results.

If women experience a visit to the outpatient clinic as a hugh problem, it is
possible to participate in the study by self-sampling. In that case women are
asked to perform a self-sampling at home and send the sample by mail for HPV
testing and cytological examination.

In case the result of an abnormal cervical smear or a positive hrHPV test, a
follow-up visit will be scheduled for additional colposcopy.If a high-grade
pre-malignant lesion is diagnosed during colposcopy, the subject will be
treated according to the current Dutch guidelines.

The possible benifit for the participating subject may be the earlier detection
of a cervical lesion in comparison to those subjects who only participate in
the population based screening program.

Risks and burden are linked to protocol procedures, such as cervical sampling
and, if applicable, colposcopy. Although these are routine procedures, carried
out by medical qualified personnel, they may cause side effects or discomfort
to the subject. However, it is expected that these procedures will generally be
well tolerated.