An observational controlled study on vaginal blood flow and sexual functioning after early stage cervical cancer treatment

Women that have been treated for cervical cancer reported more sexual
complaints, such as diminished lubrication, dyspareunia, vaginal shortening
and/or tightening, both in comparison to prior to treatment as well as compared
to healthy controls. The primary treatment for women with early-stage (FIGO IA2
* IIA) cervical cancer is radical hysterectomy with pelvic lymphadenectomy
(RHL). Nowadays the most used procedure for stage IB and IIA carcinoma of the
uterine cervix is a modification of the Wertheim operation with influences of
Meigs and/or Okabayashi (RHL-WM or RHL-WO, Piver type III). At the LUMC, since
2001, conducting a nerve sparing RHL (RHL-WM-NS) is the standard way of
treatment for early stage cervical cancer. At the Amsterdam Medical Centre,
surgery among cervical cancer patients is conducted by means of a conventional
radical hysterectomy using the Okabayashi method (RHL-WO).
With the conventional RHL (RHL-WM or RHL-WO), the pelvic autonomic nerves
(especially the hypogastric plexus) are damaged. This leads to disrupted
autonomic innervation of the bladder, rectum, and the blood vessels in the
vaginal wall. Consequently, patients often experience various postoperative
symptoms concerning, amongst others, sexual functioning. For example, the
(increase in) vaginal blood flow in response to sexual stimuli is innervated by
the hypogastric nerve. Damage to the hypogastric nerves disrupts the vaginal
response to sexual stimuli, which may result in vaginal dryness during sexual
intercourse and dyspareunia. Some of these complaints may be prevented by
conducting a nerve sparing RHL, in order to prevent damage to the pelvic
autonomic nerves.
A preliminary pilot-study by Pieterse et al. (2008, CME protocolno. P05.095)
showed that there was a trend (p=.097) for less disrupted vaginal blood flow in
response to sexual stimuli in patients after nerve-sparing RHL (RHL-WM-NS)
compared to women that received conventional RHL because the nerve sparing was
conducted without success (RHL-WM). Vaginal blood flow in nerve-sparing RHL
showed to be comparable to women after simple hysterectomy (AUE) and women
without hysterectomy.
In approximately one third of these women, surgery is followed by postoperative
external beam radiation therapy (RT). Postoperative RT is conducted when
certain risk factors are observed during surgery and prognosis increases after
postoperative RT. It is expected that RT causes vaginal changes due to
radiation-induced vaginal fibrosis, stenosis and mucosal atrophy, and may
therefore also be related to a decreased vaginal response to sexual stimuli.
Previous studies have shown that women that were treated with RT more often
reported decreased lubrication, dyspareunia and vaginal shortening and/or
tightening (Pieterse 2013; Brand 2006; Jensen 2003). These sexual complaints
may be partly explained by a decreased vaginal blood flow response after RT.
Although the results in terms of survival after treatment for low stage
cervical carcinoma (surgery, if indicated followed by adjuvant radiation
therapy) are reasonably good, morbidity due to treatment, among which long-term
sexual problems, is still a matter of concern. Problems with sexuality may
affect quality of life. After treatment, several symptoms related to sexual
dysfunction appeared to be the primary sources of symptom-induced distress.
This study among women treated with a conventional RHL-WO will make it possible
to judge the individual influence of the different treatment modalities on the
vaginal response and subjective sexual arousal to sexual stimuli. The results
of this study are important in order to develop tailored patient information
and support regarding sexuality for women that will be treated for early stage
cervical cancer and cervical cancer survivors.

This study will investigate a comparison group of women treated with a
conventional (non-nerve sparing) RHL for cervical cancer (CC) at the Academic
Medical Centre (AMC). Together with the data collected of women treated with a
nerve sparing radical hysterectomy for CC without RT (P05.095) and with RT
(P10.066), and age-matched healthy controls (P05.095), this study will provide
information on the individual contribution of (nerve sparing) radical
hysterectomy with or without postoperative radiotherapy as a cause for a
disrupted vaginal perfusion response to sexual stimuli after treatment.
The results of this study are important in order to develop tailored patient
information and support regarding sexuality for women that will be treated for
early stage cervical cancer and cervical cancer survivors.
The assumption is that the group of women treated with a conventional RHL will
show a more disrupted vaginal perfusion response on sexual stimuli than the
group of women treated with a nerve sparing RHL, while the subjective sexual
arousal to the sexual stimuli will be comparable. The group of women treated
with nerve sparing RHL will be comparable to the group of healthy controls with
respect to the vaginal perfusion response. Furthermore, it will be
exploratively investigated whether RT will annihilate the expected preserved
vaginal perfusion response after nerve sparing RHL (due to the possible
radiation-induced consequences for the vaginal tissue).

An observational study will be conducted among women treated with a
conventional (non-nerve sparing) radical hysterectomy for CC. Among this group
of women, the vaginal pulse amplitude (VPA) and subjective sexual arousal in
response to sexual stimuli will be measured using vaginal photoplethysmography.
The results obtained in the current study will be compared with the data of a
group of women treated with a nerve-sparing RHL without external beam radiation
(P05.095) or nerve-sparing RHL without external beam radiation (P10.066) and
age-matched historical controls (from P05.095) by using a between (4 subject
groups) X within (VPA) study design.
The study will be conducted multicenter: The photoplethysmography will be
performed at the LUMC. Also, the study will be coordinated at the LUMC.
Participants will be recruited at the AMC.

Potential participants will be recruited by reviewing medical files by the
principal investigator together with the investigator on main inclusion
criteria. Eligible potential participants will receive a letter at their home
address concerning information of this study. Women can let the researcher know
by e-mail or telephone within two weeks whether they are interested in
participation. After two weeks the researcher will contact the women who did
not respond, by telephone. Women that are interested to participate will
receive explanation about the study in detail on the phone from the researcher
and subsequently screened on in- and exclusion criteria. After verbal consent
of participation during the telephone call, an appointment will be made and the
participant receive questionnaires at home. The participants are asked to fill
them in prior to their visit at the LUMC and hand them over after filling in
the written informed consent.
Part 1 (duration 0.5 hour): During the first part of the visit, written
informed consent will be obtained, in which confidentiality, anonymity and the
opportunity to withdraw from the experiment without penalty is assured, prior
to measurements. The participants* written consent to participate in the study
must be obtained after a full explanation has been given of this protocol. This
explanation is delivered together with the informed consent form. After that,
the participant hands over the questionnaires. In case menopausal status should
be verified, a blood sample is then taken by the medical doctor and principal
investigator of this project, an assistant under his supervision or the
so-called *blood lab* of the LUMC. Subsequently, the participant will shortly
be asked if anything has changed with regard to their health since they were
screened by telephone. Furthermore, the researcher will explain all procedures
of the vaginal plethysmography in detail. The researcher also shows and
explains the devices used in the genital measurement.
Part 2 (duration 1 hour): Experimental session with neutral and erotic films,
and vaginal plethysmography. After this experimental procedure, a brief
exit-interview will take place.
Participating in this study will not cause any (physical) harm for the
participants. The vaginal plethysmographs are sterilized according to LUMC
regulations. It is possible that women find it bothersome to watch the erotic
excerpts or inserting the plethysmograph. However, no harmful events due to its
use have been documented. The chance that women experience pain while inserting
the plethysmograph is most likely very small, because it is small, has the size
of a small tampon and is made out of smooth material. Furthermore, subjects may
use lubricant to insert the plethysmograph. Subjects can leave the study at any
time for any reason if they wish to do so without any consequences. Apart from
the expected benefits from for future support of cervical cancer patients,
there will be no benefits for the study participants.