From Active Compound to Target Epithelium: Local Delivery, Preclinical Model Validity, and Clinical Endpoint Interpretation in Topical Therapy for HPV-Associated Lower Genital Tract Disease—A Narrative Review
- 1“Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- 2Cuza Voda Hospital, 700038 Iasi, Romania
- 3Department of Ophthalmology, Emergency Clinical Hospital “Prof. Dr. Nicolae Oblu”, 700309 Iasi, Romania
Abstract
Cervical excision increases the risk of preterm birth, while active surveillance for grade 2 cervical intraepithelial neoplasia offers no active treatment. Topical therapy for human papillomavirus (HPV)-associated lower genital tract disease could address this gap, yet no agent is approved for intraepithelial neoplasia of the cervix, vagina, or vulva, and a 2026 systematic review left open whether cervical treatment reduces progression. Scarcity does not explain this: 52 randomized trials have evaluated adjuvant treatment after excision, but heterogeneity in phenotype, comparator, and endpoint, and incomplete access to primary reports limit their interpretability. Three problems recur. First, the target epithelial population differs by phenotype and mechanism, yet local exposure was seldom characterized, although measurement strategies are set out here. Second, some antiviral claims rely on systems that do not reproduce the differentiation-dependent HPV life cycle. Third, endpoints are read against spontaneous regression approaching the effect sought. Randomized evidence supports imiquimod as a non-surgical option for appropriately selected women with vulvar high-grade squamous intraepithelial lesions; cervical conclusions depend on comparator and endpoint. We propose a conceptual eight-element sequence from clinical intention to inference, an interpretive aid, and not a validated appraisal instrument. Future studies should prespecify these elements and characterize exposure where feasible.
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BibTeX
@article{gavril2026from,
title = {{From Active Compound to Target Epithelium: Local Delivery, Preclinical Model Validity, and Clinical Endpoint Interpretation in Topical Therapy for HPV-Associated Lower Genital Tract Disease—A Narrative Review}},
author = {Sandra Teodora Gavril and Răzvan Popovici and Iustina Petra Solomon Condriuc and Vasile Adrian Sescu and Raluca Haba and Raluca Anamaria Mogoș and Claudia Florida Costea and Alexandru Cărăuleanu},
journal = {Journal of clinical medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15197631},
url = {https://europepmc.org/article/PMC/PMC13666372},
note = {CC BY},
}
RIS
TY - JOUR
TI - From Active Compound to Target Epithelium: Local Delivery, Preclinical Model Validity, and Clinical Endpoint Interpretation in Topical Therapy for HPV-Associated Lower Genital Tract Disease—A Narrative Review
AU - Sandra Teodora Gavril
AU - Răzvan Popovici
AU - Iustina Petra Solomon Condriuc
AU - Vasile Adrian Sescu
AU - Raluca Haba
AU - Raluca Anamaria Mogoș
AU - Claudia Florida Costea
AU - Alexandru Cărăuleanu
PY - 2026
DA - 2026/10/01
JO - Journal of clinical medicine
DO - 10.3390/jcm15197631
UR - https://europepmc.org/article/PMC/PMC13666372
AB - Cervical excision increases the risk of preterm birth, while active surveillance for grade 2 cervical intraepithelial neoplasia offers no active treatment. Topical therapy for human papillomavirus (HPV)-associated lower genital tract disease could address this gap, yet no agent is approved for intraepithelial neoplasia of the cervix, vagina, or vulva, and a 2026 systematic review left open whether cervical treatment reduces progression. Scarcity does not explain this: 52 randomized trials have evaluated adjuvant treatment after excision, but heterogeneity in phenotype, comparator, and endpoint, and incomplete access to primary reports limit their interpretability. Three problems recur. First, the target epithelial population differs by phenotype and mechanism, yet local exposure was seldom characterized, although measurement strategies are set out here. Second, some antiviral claims rely on systems that do not reproduce the differentiation-dependent HPV life cycle. Third, endpoints are read against spontaneous regression approaching the effect sought. Randomized evidence supports imiquimod as a non-surgical option for appropriately selected women with vulvar high-grade squamous intraepithelial lesions; cervical conclusions depend on comparator and endpoint. We propose a conceptual eight-element sequence from clinical intention to inference, an interpretive aid, and not a validated appraisal instrument. Future studies should prespecify these elements and characterize exposure where feasible.
SN - 2077-0383
ER -