---
title: "Neoadjuvant NAC‑TPF permits radiotherapy avoidance in HPV‑associated oropharyngeal cancer: Phase I"
id: "british-journal-of-cancer-1-neoadjuvant-triplet-chemotherapy-enables-radiotherapy-avoidance-in-human"
canonical_url: "https://medichelpline.com/clinical-feed/british-journal-of-cancer-1-neoadjuvant-triplet-chemotherapy-enables-radiotherapy-avoidance-in-human"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "British Journal of Cancer"
source_url: "https://www.nature.com/articles/s41416-026-03610-y"
published_at: "2026-09-05T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Neoadjuvant NAC‑TPF permits radiotherapy avoidance in HPV‑associated oropharyngeal cancer: Phase I
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/british-journal-of-cancer-1-neoadjuvant-triplet-chemotherapy-enables-radiotherapy-avoidance-in-human
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** British Journal of Cancer
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41416-026-03610-y)
- **Published At:** 2026-09-05T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This multicentre Phase II trial evaluated a de‑escalation strategy using upfront **neoadjuvant chemotherapy** with docetaxel, cisplatin and 5‑fluorouracil (**NAC‑TPF**) in patients with resectable **HPV‑associated oropharyngeal squamous cell carcinoma (OPSCC)**. - Eligible patients received three cycles of NAC‑TPF followed by transoral surgery; postoperative radiotherapy (PORT) or postoperative chemoradiotherapy (POCRT) were planned as per initial inclusion criteria if surgery was performed. - The primary endpoint was centrally reviewed pathological complete response (**pCR**) rate after NAC‑TPF. The study also measured tumour HPV RNA levels, plasma circulating tumour (**ctHPV**) DNA, and quality of life (QOL). - Of 32 eligible participants, 30 proceeded to transoral surgery after NAC‑TPF; R0 resection was achieved in 31 patients. - The observed pCR rate at the primary site and lymph nodes was 65.6%; the virological complete response rate at both primary and nodal sites was 64.5%. - Postoperative radiotherapy or chemoradiotherapy was avoided in 91% of patients in this cohort. - Twenty‑three patients had undetectable **ctHPV DNA** after NAC‑TPF, consistent with treatment effect on circulating viral DNA. - All assessed QOL scores recovered to baseline values or improved within one year after treatment. - The study did not meet its pre‑specified primary endpoint despite achieving a clinically meaningful pCR and high rates of radiotherapy avoidance. - Data are available on request from the corresponding author; the trial is registered (jRCT1041220029).
## Clinical Analysis & Structured Key Points
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[nature](https://www.nature.com/) 2. [british journal of cancer](https://www.nature.com/bjc) 3. [articles](https://www.nature.com/bjc/articles?type=article) 4. article * Article * Published: 05 September 2026 Clinical Study # Neoadjuvant triplet chemotherapy enables radiotherapy avoidance in human papillomavirus–associated oropharyngeal cancer: a multicentre Phase II trial * [Tomoya Yokota](https://www.nature.com/articles/s41416-026-03610-y#auth-Tomoya-Yokota-Aff1) [ORCID: orcid.org/0000-0001-7327-7949](https://orcid.org/0000-0001-7327-7949)[1](https://www.nature.com/articles/s41416-026-03610-y#Aff1), * [Toyonori Tsuzuki](https://www.nature.com/articles/s41416-026-03610-y#auth-Toyonori-Tsuzuki-Aff2) [ORCID: orcid.org/0000-0002-4855-4366](https://orcid.org/0000-0002-4855-4366)[2](https://www.nature.com/articles/s41416-026-03610-y#Aff2), * [Tetsuro Onitsuka](https://www.nature.com/articles/s41416-026-03610-y#auth-Tetsuro-Onitsuka-Aff3)[3](https://www.nature.com/articles/s41416-026-03610-y#Aff3), * [Akira Iizuka](https://www.nature.com/articles/s41416-026-03610-y#auth-Akira-Iizuka-Aff4)[4](https://www.nature.com/articles/s41416-026-03610-y#Aff4), * [Yohei Ouchi](https://www.nature.com/articles/s41416-026-03610-y#auth-Yohei-Ouchi-Aff5)[5](https://www.nature.com/articles/s41416-026-03610-y#Aff5), * [Terushige Mori](https://www.nature.com/articles/s41416-026-03610-y#auth-Terushige-Mori-Aff5)[5](https://www.nature.com/articles/s41416-026-03610-y#Aff5), * [Kiyoaki Tsukahara](https://www.nature.com/articles/s41416-026-03610-y#auth-Kiyoaki-Tsukahara-Aff6)[6](https://www.nature.com/articles/s41416-026-03610-y#Aff6), * [Kenji Hanyu](https://www.nature.com/articles/s41416-026-03610-y#auth-Kenji-Hanyu-Aff6)[6](https://www.nature.com/articles/s41416-026-03610-y#Aff6), * [Takashi Mukaigawa](https://www.nature.com/articles/s41416-026-03610-y#auth-Takashi-Mukaigawa-Aff7)[7](https://www.nature.com/articles/s41416-026-03610-y#Aff7), * [Torahiko Nakashima](https://www.nature.com/articles/s41416-026-03610-y#auth-Torahiko-Nakashima-Aff8)[8](https://www.nature.com/articles/s41416-026-03610-y#Aff8), * [Hideoki Uryu](https://www.nature.com/articles/s41416-026-03610-y#auth-Hideoki-Uryu-Aff8)[8](https://www.nature.com/articles/s41416-026-03610-y#Aff8), * [Go Omura](https://www.nature.com/articles/s41416-026-03610-y#auth-Go-Omura-Aff9)[9](https://www.nature.com/articles/s41416-026-03610-y#Aff9), * [Hiromu Nakamura](https://www.nature.com/articles/s41416-026-03610-y#auth-Hiromu-Nakamura-Aff10)[10](https://www.nature.com/articles/s41416-026-03610-y#Aff10), * [Hirokazu Uemura](https://www.nature.com/articles/s41416-026-03610-y#auth-Hirokazu-Uemura-Aff11)[11](https://www.nature.com/articles/s41416-026-03610-y#Aff11), * [Daisuke Nishikawa](https://www.nature.com/articles/s41416-026-03610-y#auth-Daisuke-Nishikawa-Aff12)[12](https://www.nature.com/articles/s41416-026-03610-y#Aff12), * [Satoshi Kano](https://www.nature.com/articles/s41416-026-03610-y#auth-Satoshi-Kano-Aff13)[13](https://www.nature.com/articles/s41416-026-03610-y#Aff13), * [Yasuto Akiyama](https://www.nature.com/articles/s41416-026-03610-y#auth-Yasuto-Akiyama-Aff4)[4](https://www.nature.com/articles/s41416-026-03610-y#Aff4), * [Tsuyoshi Onoe](https://www.nature.com/articles/s41416-026-03610-y#auth-Tsuyoshi-Onoe-Aff14)[14](https://www.nature.com/articles/s41416-026-03610-y#Aff14), * [Shunsuke Oyamada](https://www.nature.com/articles/s41416-026-03610-y#auth-Shunsuke-Oyamada-Aff15)[15](https://www.nature.com/articles/s41416-026-03610-y#Aff15) & * … * [Takuhiro Yamaguchi](https://www.nature.com/articles/s41416-026-03610-y#auth-Takuhiro-Yamaguchi-Aff16)[16](https://www.nature.com/articles/s41416-026-03610-y#Aff16) Show authors [_British Journal of Cancer_](https://www.nature.com/bjc) (2026) [Cite this article](https://www.nature.com/articles/s41416-026-03610-y#citeas) [ Save article ](https://www.nature.com/articles/s41416-026-03610-y/save-research?_csrf=FLXCgQEEFSwQlxgLmcZRYdZlTHQ729Qd) [ View saved research ](https://www.nature.com/saved-research) ## Abstract ### Background This prospective Phase 2 trial assessed a novel de-escalation strategy for upfront neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (NAC-TPF) to avoid postoperative radiotherapy (PORT) and chemoradiotherapy (POCRT) for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). ### Methods Patients with HPV-associated resectable OPSCC were enrolled. Invasive surgery or PORT/POCRT was an inclusion criterion if upfront surgery was performed. Treatment started with three cycles of NAC-TPF, followed by surgery. The primary endpoint was the centrally reviewed pathological complete response (pCR) rate after NAC-TPF. Levels of high-risk HPV RNA in tumor specimens and plasma circulating tumor (ct) HPV DNA, and quality of life (QOL) scores were assessed. ### Results Of 32 eligible patients, 30 patients underwent transoral surgery after NAC-TPF. R0 resection was confirmed in 31 patients. pCR and virological complete response rate at both the primary site and lymph nodes were 65.6% and 64.5%, respectively. No PORT/POCRT was performed in 91%. All QOL scores recovered to baseline values or improved within 1 year. Twenty-three patients showed undetectable ctHPV DNA levels after NAC-TPF. ### Conclusion Although the primary endpoint was not met, NAC-TPF in HPV-associated resectable OPSCC achieved clinically meaningful pCR, enabling avoidance of PORT/POCRT in the majority of patients. (Clinical trial registration numbers: jRCT1041220029) ![](https://media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41416-026-03610-y/MediaObjects/41416_2026_3610_Figa_HTML.png) This is a preview of subscription content, [access via your institution](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41416-026-03610-y) ## Access options [ Access through your institution ](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41416-026-03610-y) Subscribe to this journal Receive 24 print issues and online access 251,40 € per year only 10,48 € per issue [Learn more](https://www.nature.com/bjc/subscribe) Buy this article * Purchase on SpringerLink * Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout ### Additional access options: * [Log in](https://idp.nature.com/authorize/natureuser?client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41416-026-03610-y) * [Learn about institutional subscriptions](https://www.springernature.com/gp/librarians/licensing/license-options) * [Read our FAQs](https://support.nature.com/en/support/home) * [Contact customer support](https://www.springernature.com/gp/contact) **Fig. 1** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03610-y/MediaObjects/41416_2026_3610_Fig1_HTML.png) **Fig. 2** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03610-y/MediaObjects/41416_2026_3610_Fig2_HTML.png) **Fig. 3: Changes in quality-of-life scores on the 30-item European Organization for Research and Treatment of Cancer Core’s Quality of Life Questionnaire by Function Score.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03610-y/MediaObjects/41416_2026_3610_Fig3_HTML.png) ### Explore related subjects Discover the latest articles and news in related subjects. * [Chemotherapy](https://www.nature.com/subjects/chemotherapy) * [Head and neck cancer](https://www.nature.com/subjects/head-and-neck-cancer) ## Data availability The data generated in this study are not publicly available due to patient privacy or consent but are available upon reasonable request from the corresponding author. ## References 1. 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