Nov 2016 OB/GYN Dr.

Nunn Janushan Sasitharan

A Retrospective Study into Short-Term Efficacy of

Trichloroacetic Acid in the Treatment of Cervical
Intraepithelial Neoplasia

Introduction
In 2016 it is estimated that there were 12990 new cases of cervical cancer
(Cancer of the cervix Uteri - SEER stat fact sheets, 2016) The most common risk
factor is known to be Human Papilloma Virus (HPV). Different serotypes are
more dangerous than others. HPV is a common sexually transmitted disease.
About 79 million Americans are currently infected with HPV. (CDC, 2016)
Serotypes 16 and 18 of HPV are now known to be the most dangerous and cause
the most severe form of CIN.
Management approach varies with the severity of the neoplasia and age of the
patient. Conservative treatment is preferred in younger patients and less severe
CIN. High grade CIN is usually treated with loop excision or conisation, however
this is associated with increased preterm births. This retrospective study is
looking into conservative and effective management of CIN with the use of
topical 85% Trichloroacetic Acid, which is proving an effective non surgical
approach to treatment.
Trichloroacetic acid causes protein denaturation and cell death. The aim of the
study was to establish the short term efficacy and tolerability of a single topical
85% Trichloroacetic acid treatment for CIN 1-3.
CIN is separated into 3 categories:
1. CIN 1 Mild dysplasia
2. CIN 2 moderate to marked dysplasia
3. CIN 3 severe carcinoma in situ
(Cervical dysplasia, 2016)

Materials and Methods:

This was a retrospective study which included all women who were undergoing
treatment with Trichloroacetic acid between the dates of September 2012 and
January 2015. The study was approved by the Institutional review board of the
Medical University of Vienna.

The inclusion criteria for the study were women who had biopsy confirmed CIN
1 which persisted for a minimum of 6 months or CIN 2-3. Patients who refused a
biopsy and requesting a See and Treat could also be included in the study
based on cytology suspected CIN. Which is divided into low grade squamous
intraepithelial lesions and high grade (LSIL and HSIL). If there were no signs of
invasion on colposcopy or negative histology even with LSIL or HSIL, they would
be excluded from the study.

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Nov 2016 OB/GYN Dr.Nunn Janushan Sasitharan

Patients included in the study were also asked to report their level of pain on a
visual analogue scale of zero to ten. Zero being no pain and ten being the worst
pain they have ever felt immediately after the administration of the
Trichloroacetic acid.
Patients were asked to refrain from sexual intercourse for 2 weeks, opt for
showering over bathing for 4 weeks and using sanitary pads instead of tampons.
If patients were found to have type 16 or 18 HPV, they would be treated with
endocervical curettage , but if it persists after 8 weeks, the patient wouldnt be
able to continue with the Trichloroacetic acid treatment as there is insufficient
data on the safety of continues applications.

Results

241 patients with CIN 1-3 took part in this retrospective study. The median age
of the women was 31 and the 25th and 75th percentiles were 26 and 35.
The patients were categorised into high grade and low grade CIN.
179 were in the High grade.
62 were in the Low grade.

High grade squamous intraepithelial lesions, regression rate was:

87.7% (95% CI 82.0-92.1)
the remission rate was:
80.3% (95% CI 73.3-85.5)

Low grade squamous intraepithelial lesions, remission rate was:

82.3% (95% CI 70.5-90.8)

High Risk HPV, which includes types 16, 18 and others.

16 was found in 53.7% of patients tested
18 was found in 7.3% of patients tested
Others types were found in 39% of patients tested

HPV clearance for types 16, 18 and all high risk types was:
16: 73.5% (95% CI 64.6-81.2)
18: 75% (95% CI 47.6-92.7)
Other high risk: 62.8% (95% CI 56.1-69.3)

The VAS Median pain score was 3.0 out of 10.0 (25th, 75th percentiles were 2.3
and 4.3.

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Nov 2016 OB/GYN Dr.Nunn Janushan Sasitharan

Discussion
The study showed that the use of Trichloroacetic acid in a single treatment for
CIN 1-3 showed a huge response with high clearance rates of HPV after 8 weeks.
With minimal difference in the outcome of treatment of high and low grade CIN ,
it could be deduced that treatment didnt vary much with HPV type.

There is also a huge benefit in that fact there wasnt a very high VAS (pain index)
with a value of 3.0. This is quite low as peripheral IV cannula insertion without
lidocaine is reported to be 7.0 and with is also 3.0.

The use of Trichloroacetic acid treatment in men suffering from anal

intraepithelial Neoplasia and tested positive for HIV, proved useful.
In 98 patients 79% of lesions treated went from HSIL and regressed to LSIL.

Most studies and treatment options with regards to Trichloroacetic acid have
been limited to condyloma acuminate. Some other studies with treatment have
shown positive outcomes, even at 50% Trichloroacetic acid.

Although there are various other treatment options for HPV lesions, heat
treatments like cold coagulation and laser. Or cold treatments like cryotherapy.
These require a specialist with training and special equipment. Thats why
Trichloroacetic acid would be beneficial , as its application is easier, more cost
effective, and very low risk of complications.

This study did have some limitations such as:

missing control group
missing data
patients were all from one location
The See and treat approach taken, doesnt factor into long term outcomes.

Although this study has some flaws, there doesnt seem to be many other reports
on the use of Trichloroacetic acid in the treatment of CIN, so it should be
considered a step in the right direction.

References
CDC. (2016, November 4). Genital HPV infection - fact sheet. Retrieved November
28, 2016, from http://www.cdc.gov/std/hpv/stdfact-hpv.htm

Cervical dysplasia. (2016, November 1). Retrieved November 28, 2016, from
https://medlineplus.gov/ency/article/001491.htm