Adjuvant vaccination against HPV in surgical treatment of CIN lesions, a Randomised Controlled Trial.

Cervical cancer is preceded by precursor stages: Cervical Intraepithelial
Neoplasia Neoplasia, (CIN). These CIN abnormalities are caused by the Human
Papilloma virus (HPV) and are mostly found in women in their reproductive age.
There is an effective prophylactic vaccine against HPV, given since 2009 in the
Netherlands to girls of 12 and 13 years old. This vaccine is very effective
against the occurrence of CIN abnormalities in this group. Also, in older women
who already had an HPV infection, without CIN abnormalities, the vaccine has
shown to be effectively for preventing to develop CIN. The current treatment of
CIN II-III (moderate to severe precursor stages) is surgical removal of a part
of the cervix. This is called a Loop Electrosurgical Excision Procedure (LEEP).
This treatment has a recurrence rate or residual rate up to 17%. A secondary
surgical treatment is necessary in these women. Surgical treatments are
associated with bleeding, narrowing of the cervix and infection. The biggest
problem, with sometimes lifelong consequences, are the obstetric complications,
especially premature birth. This becomes more frequent and more serious after
repeated surgical intervention. The (repeated) treatment is also a burden of
the women and her loved ones.
HPV is also known to cause other forms of cancer later in life(including pubic
cancer, vaginal cancer and anus cancer). This chance is reduced when the virus
is cleared.

Hypothesis
Vaccination with the HPV vaccine at the time of surgical intervention reduces
the risk of recurrent CIN
abnormalities in unvaccinated women, by an enhanced immune response. This will
additionally reduce the risk of other HPV-initiated cancers. The treatment of
women
with a CIN abnormalities will thus become more effective and cost-efficient.

Evaluate the efficacy of nonavalent HPV vaccination in women with a CIN lesion
who will undergo or have undergone a LEEP in preventing recurrent CIN II-III
after 24 months.

Randomized, double blinded, placebo controlled trial

Intervention: 0.5 ml nonavalent HPV vaccination. Comparator: placebo
vaccination.
Dosing scheme: preferable at day of LEEP(or within 4 weeks), at 2 and 6 month
follow-up visits.

The syringes of the placebo and the vaccine will be identical. At the day of
LEEP or within 4 weeks after the
LEEP the first vaccination should be administered. The HPV vaccine should be
administered according a 3-
dose (0,2 and 6 months) schedule. Vaccination is by intramuscular injection in
the deltoid region of the
upper arm or in the higher anterolateral area of the thigh. All three doses
should be given within a 1-year
period . We choose a placebo as comparator to minimize selection bias.

All included patients receive regular treatment according to the latest Dutch
guideline. Risk and burden are linked to protocol procedures. These are
routine procedures and carried out by medical qualified personnel. Adverse
events and symptoms of the vaccination will be evaluated. The vaccinations
and/or the placebo injections may cause side effects or discomfort. However, it
is expected that these procedures will generally be well tolerated.