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HAL-PDT Doubles Response Rate Versus Placebo in CIN2 Patients at Six Months
In a prespecified subgroup analysis of a phase III randomised controlled trial, hexaminolevulinate photodynamic therapy (HAL-PDT) achieved a response rate of 49.2% compared with 22.6% in the placebo group at six months — more than double the placebo rate — in patients with histologically confirmed cervical intraepithelial neoplasia 2 (CIN2) (P=0.001). The safety profile was comparable between arms, with no statistically significant difference in treatment-related adverse events, supporting HAL-PDT as a potentially viable non-surgical option for this population.
What Was Studied
The central question was whether HAL-PDT — combining a 5% hexaminolevulinate ointment with LED light source activation — could produce meaningful disease response and histological regression in women with CIN2, with an acceptable safety burden. The primary outcome was the composite response rate at six months following the initial treatment cycle, alongside secondary assessments of histological regression, colposcopic lesion clearance, and high-risk HPV (HR-HPV) clearance at twelve months.
How It Was Studied
This report presents a subgroup analysis of the APRICITY study, an international, multicentre, randomised, double-blind, placebo-controlled phase III clinical trial conducted between October 2020 and July 2023 across 61 medical centres in seven countries. A total of 182 patients with histologically confirmed CIN2 were included and randomly assigned in a 2:1 ratio — 120 to the HAL-PDT group and 62 to the placebo group (placebo ointment with a non-illuminating device). Baseline characteristics were well balanced between groups. Follow-up extended to twelve months, enabling assessment of both short-term disease response and longer-term virological outcomes.
What Was Observed
- Primary response rate at six months: HAL-PDT produced a response in 49.2% of treated patients versus 22.6% in the placebo group — a difference of more than 26 percentage points that was highly statistically significant (P=0.001). This represents the primary efficacy signal of the trial.
- Histological regression and colposcopic clearance: Histological regression occurred in 57.5% of the HAL-PDT group compared with 30.6% in placebo recipients (P=0.001). Colposcopic lesion clearance followed a similar pattern, with 60.6% in the HAL-PDT group versus 32.7% in the placebo group (P=0.001), further corroborating the biological activity of the intervention.
- Disease progression risk: The risk of progression to higher-grade disease appeared approximately 45% lower with HAL-PDT than placebo (RR=0.55, 95% CI: 0.29–1.06); however, this difference did not reach conventional statistical significance (P=0.068), and the wide confidence interval means this estimate is imprecise and should be interpreted cautiously.
- HR-HPV clearance and safety: At twelve months, HR-HPV clearance rates in the HAL-PDT group reached 45.9% for any high-risk subtype, 58.8% specifically for HPV 16, and 55.4% for HPV 16/18 combined. Treatment-related adverse events occurred in 31.1% of HAL-PDT recipients versus 25.8% in the placebo group — a non-significant difference (P=0.496) — and reported events such as increased vaginal discharge, abdominal pain, and vulvovaginal discomfort were mild and resolved without intervention.
Why This Matters
CIN2 represents a clinical decision point where patients and clinicians must weigh the risks of surgical intervention against the possibility of spontaneous regression. HAL-PDT, as demonstrated here, offers a non-surgical mechanism that produced measurable histological and virological benefit without a significant increase in adverse events relative to placebo. The authors specifically frame this as a fertility-preserving and cervical-integrity-maintaining alternative, addressing a recognised unmet need for patients who wish to avoid excisional procedures and their associated reproductive risks.
How to Read This Result
These findings are encouraging and emerge from a well-designed phase III randomised trial with balanced groups and multicentre recruitment, but because this report is a prespecified subgroup analysis rather than the primary trial outcome, and because the disease progression endpoint did not reach statistical significance, conclusions about longer-term protective effects should be considered preliminary pending full trial reporting.
Limitations
The abstract does not explicitly report study limitations.