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HPV status and therapeutic initial strategy impact on survival and oncologic outcomes: 5-year results from the multicentric prospective cohort of oropharyngeal cancers Papillophar



After the 2 years of follow-up, we aimed to evaluate at 5 years the impact of human papillomavirus (HPV) status, tobacco, and initial treatment approach on progression-free survival (PFS) and overall survival (OS) of patients with oropharyngeal cancer (OPC) in France.


Papillophar study was designed as a prospective cohort of 340 OPC patients in 14 French hospitals. HPV-positive status (21.7%) was defined with PCR (positivity for HPV DNA and E6/E7 mRNA). Cox proportional hazard models were used to assess the relationship between PFS, OS, HPV, and other prognostic factors. The combined effect of HPV status with smoking, stage, or initial treatment on PFS was also evaluated.


HPV-pos patients had better PFS than HPV-neg patients (HR = 0.46; 95% CI: 0.29–0.74), and worse for older patients (HR for 5-year age increase = 1.14), UICC stage 4 from the 7th TNM classification compared to stage 1–2 (HR = 2.58; CI: 1.33–5.00), and those having had radiotherapy (HR = 2.07; 95% CI: 1.36–3.16) or induction chemotherapy (HR = 2.11; 95% CI: 1.32–3.38) instead of upfront surgery. HPV-neg patients encountered a larger incidence of loco-regional disease than HPV-pos patients (31.5% and 14.0%, respectively, p = 0.0001). Distant metastases proportion was similar. HPV-neg patients developed more second primary tumor than HPV-pos patients (11.7% vs. 3.3%, p = 0.02).


5-year follow-up confirms the specifically improved prognosis in HPV-positive patients. The prognosis is nevertheless significantly modified through clinical and therapeutical variations.

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Fig. 1
Fig. 2



Human papillomavirus


Progression-free survival


Overall survival


HPV positive


HPV negative


Oropharyngeal cancer


Hazard ratio


Confidence interval


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The authors thank Sarah Sahli from the Clinical Research Unit of East of Paris (URC-Est), Saint Antoine University Hospital (AP-HP) for study coordination and logistics. They thank all members of the Papillophar Group: G. Agius (University Hospital, Poitiers), S. Albert (AP-HP, Bichat Hospital; University Paris 7, Paris), E. Babin (University Hospital, Caen), C. Bach (Foch Hospital, Suresnes), J.M. Badet (Jean Minjoz University Hospital, Besançon), C. Badoual (AP-HP, Georges Pompidou Hospital and University Paris 5, Paris), A.C. Baglin (Foch Hospital, Suresnes), A. Beby Defaux (University Hospital, Poitiers), C. Bertolus (AP-HP, Pitié-Salpétrière Hospital and University Paris 6, Paris), K. Blanc-Fournier (François Baclesse Regional Centre, Unicancer, Caen), E. Cassagneau (Hotel-Dieu University Hospital, Nantes), V. Dalstein (Maison Blanche University Hospital, Reims), C. Debry (Hautepierre University Hospital, Strasbourg), D. de Raucourt (François Baclesse Regional Centre, Unicancer, Caen), M.D. Diebold (Maison Blanche University Hospital, Reims), S. Hans (AP-HP, Georges Pompidou Hospital; University Paris 5, Paris), M. Hourseau (AP-HP, Bichat Hospital; University Paris 7, Paris), B. Kantelip (Jean Minjoz University Hospital, Besançon), R.Lacave (AP-HP, Tenon Hospital, Paris; UPMC-Sorbonne Universities, Paris), E. Lechapt Zalcman (University Hospital, Caen), M. Lefevre (AP-HP, Tenon Hospital, Paris; UPMCSorbonne Universities, Paris), J. Lerat (University Hospital, Limoges), P. Levillain (University Hospital, Poitiers), O. Mauvais (Jean Minjoz University Hospital, Besançon), A. Mechine (Hautepierre University Hospital, Strasbourg), J.C. Merol (Maison Blanche University Hospital, Reims), H. Mirghani (Gustave Roussy Centre, Unicancer, Villejuif), S. Morinière (Bretonneau University Hospital, Tours), C. Mougin (Jean Minjoz University Hospital, Besançon), C. Rousselot (Bretonneau University Hospital, Tours), T. Simon (AP-HP, Department of Clinical Pharmacology, Clinical Research Platform (URC-Est-CRC-CRB), Saint-Antoine Hospital, Paris; UPMC-Sorbonne Universities, Paris), P. Soussan (AP-HP, Tenon Hospital, Paris; UPMC-Sorbonne Universities, Paris), and A. Touzé (University Institute of Technology, Tours).


This work was funded by the Programme Hospitalier de Recherche Clinique, French Ministry of Health (grant numbers AOM 08104, AOM 11 293). The sponsor was Assistance Publique-Hôpitaux de Paris (Délégation à la Recherche Clinique et à l’Innovation). The funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to the data and had final responsibility for the decision to submit for publication.

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AR updated and analyzed the data. DC wrote the first draft. All the authors were involved in writing, review, and approval of the final manuscript.

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Correspondence to Dorian Culié.

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This study (NCT00918710) was approved by a national ethical committee and the French data protection authority.

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All participating patients provided written informed consent.

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Culié, D., Rousseau, A., Pretet, JL. et al. HPV status and therapeutic initial strategy impact on survival and oncologic outcomes: 5-year results from the multicentric prospective cohort of oropharyngeal cancers Papillophar. Eur Arch Otorhinolaryngol (2021).

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  • Oropharyngeal cancer
  • HPV
  • Prospective
  • Study
  • Multicentric
  • 5 years