Chemical Peeling Therapy Using Phenol for the Cervico-Vaginal Intraepithelial Neoplasia

Abstract

Objective: This study aimed to validate the use of liquid phenol-based chemical peeling therapy for cervical and vaginal intraepithelial neoplasia (CIN and VaIN, respectively), with the goal of circumventing obstetric complications associated with surgical treatment and to determine the factors associated with treatment resistance. Methods: A total of 483 eligible women diagnosed with CIN, VaIN, or both, participated in this study. Participants underwent phenol-based chemical peeling therapy every 4 weeks until disease clearance. Disease clearance was determined by negative Pap tests for four consecutive weeks or by colposcopy. HPV genotyping was conducted at the onset of the study and after disease clearance in select cases. Our preliminary analysis compared the recurrence and persistence rates between 294 individuals who received phenol-based chemical peeling therapy and 189 untreated patients. Results: At 2 years following diagnosis, persistent disease was observed in 18%, 60%, and 88% of untreated patients with CIN1-3, respectively, and <2% of patients with CIN who received phenol-based chemical peeling therapy. Among 483 participants, 10 immune-suppressed patients required multiple treatments to achieve disease clearance, and 7 were diagnosed with cervical cancer. Of the 466 participants, except those with cancer or immune suppression, the number of treatment sessions until CIN/VaIN clearance ranged from 2 to 42 (average: 9.2 sessions). In total, 43 participants (9.2%) underwent surgical treatment. Six patients (1.3%) experienced recurrence of CIN2 or worse, suggesting that treatment failed in 46 patients (9.9%). No obstetrical complications were noted among the 98 pregnancies following this therapy. Factors associated with resistance to this therapy include immune suppression, ages 35-39 years, higher-grade lesions, and multiple HPV-type infections. Conclusions: Phenol-based therapy is safe and effective for CINs and VaINs. Women aged < 35 years and with persistent CIN1 or CIN2 with a single HPV-type infection are suitable candidates for phenol-based chemical peeling therapy. However, this therapy requires multiple lengthy sessions.

Keywords: CIN; chemical-peeling therapy; human papillomavirus.

Figure 1

Design of the main study.

Figure 2

Two instances of CIN3, with or without the presence of VaIN2. Case-1; 24 years old woman having CIN3, HPV16-positive, Passive smoker. (A) Colposcopy finding after treating with 3% of acetic acid showing white epithelium and mosaic pattern was seen in 10 out of 12 sections of the cervix. (B) After application of liquid phenol, (C) After 11 times of treatment for 9 months. (D) After 16 times of treatment for 12 months. This case was cured with 18 times of treatment for 13 months. Case-2; 20 years old having CIN3 + VaIN2, positive with HPV16 + HPV66 + HPV6, Passive smoker. (E) Colposcopic finding after applying with 3% of acetic acid. White epithelia were seen in 12 out of 12 sections of the cervix and 6 of 12 sections of the vagina. (F) After applying with a liquid phenol, (G) After 8 times of treatment. (H) After 20 times of treatment. This case was cured with 22 times of treatment for 11 months. Both cases were treated by this therapy at 2 weeks intervals.

Figure 3

A comparison for regression and persistence between subjects undertaking phenol therapy and those without any treatment.Phenol; Subjects with phenol therapy; CIN1: N = 110, CIN2: N = 123, CIN3: N = 61. No intervention; Controls without any treatment; CIN1: N = 126, CIN2: N = 55, CIN3: N = 8. *; Probability in comparison of regressed or persisted rates in Phenol and No intervention cases was calculated in the Mann-Whitney’s test.

Figure 4

Differences in the number of treatments until clearance between different grades of CIN, and an immune-suppressed status. *; Probability in comparison of numbers of treatment until disease clearance among disease groups was calculated in the Mann-Whitne’s test. NS: Not significant.

Figure 5

Difference in the number of treatment until clearance between HPV type groups and different infection patterns. (A) HPV group, HPV16/18; HPV16 or HPV18, HGHR; higher grade high-risk types: HPV31, 33, 45, 52, 58, LGHR; lower grade high-risk types: HPV39, 51, 56, 59, 68, PHR; probable high-risk types; HPV26, 53, 66, 67, 70, 73, 82. LR/ Neg; Low-risk types: HPV6, 11, 42, 44, 54, 55, 61, 62, 71, 84, 89, and 90 or negative for HPV. (B) Single HPV type and multiple HPV type infection. *; Probability in comparison of numbers of treatment until disease clearance among disease groups was calculated in the Mann-Whitne’s test. NS: Not significant.