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Human papillomavirus independent status on pathologic response and outcomes in locally advanced cervical cancer managed with chemoradiotherapy followed by surgery
  1. Luigi Carlo Turco1,
  2. Luigi Pedone Anchora1,
  3. Camilla Fedele1,
  4. Frediano Inzani1,
  5. Alessia Piermattei1,
  6. Maurizio Martini1,
  7. Mariaconcetta Volpe2,
  8. Simona Marchetti2,
  9. Rosaria Santangelo2,
  10. Nicolò Bizzarri1,
  11. Francesco Cosentino3,4,
  12. Virginia Vargiu3,
  13. Maria De Ninno3,
  14. Gabriella Macchia3,
  15. Vincenzo Valentini5,
  16. Gianfranco Zannoni1,
  17. Giovanni Scambia1,6 and
  18. Gabriella Ferrandina1,7
  1. 1Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  2. 2Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
  3. 3Dipartimento di Oncologia, Gemelli Molise, Campobasso, Italy
  4. 4Università degli Studi del Molise Dipartimento di Medicina e di Scienze della Salute Vincenzo Tiberio, Campobasso, Italy
  5. 5Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
  6. 6Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Italy
  7. 7Università Cattolica del Sacro Cuore Sede di Roma, Rome, Italy
  1. Correspondence to Professor Giovanni Scambia, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A Gemelli IRCCS, Roma, Italy; giovanni.scambia{at}


Objective While human papillomavirus (HPV) has been shown to play a significant role in cervical cancer carcinogenesis (HPV associated cases), a considerable percentage of cervical cancers occur independently of HPV status (HPV independent).

Methods In this retrospective study of 254 locally advanced cervical cancer patients treated with chemoradiotherapy and radical surgery, HPV genotypes were determined using the Anyplex II HPV28 kit that uses multiplex, real time polymerase chain reaction technology. The primary endpoints of this study were to evaluate the complete response to chemoradiotherapy (pathologic complete response), the presence of microscopic (<3 mm, pathologic micro partial response, group 1) and macroscopic (>3 mm, pathologic macro partial response, group 2) residual carcinoma in the cervix, and the persistence of metastatic lymph nodes (group 3) in HPV independent cervical cancers. Secondary endpoints were evaluation of disease-free survival and overall survival.

Results Of 254 patients studied, 21 cases (8.3%) of cervical cancer were determined to be HPV independent. The percentage of pathologic complete response was found to be higher in the HPV associated group compared with the HPV independent group (p<0.001). In the HPV associated cervical cancer group, 5 year disease free survival was found to be 80.8% versus 59.9% in the HPV independent group (p=0.014). Overall survival was also higher in the HPV associated group (87.9%) compared with the HPV independent patients (69.4%) (p=0.023). In the multivariate analysis, the International Federation of Gynecology and Obstetrics (FIGO) stage and HPV genotypes maintained their relevant impact on pathologic complete response to chemoradiotherapy: FIGO stages IIIC1 and IIIC2 were associated with a 13-fold increased risk for the presence of metastatic lymph nodes compared with group 1 (p<0.001). HPV independent cervical cancers showed the highest risk for the development of macroscopic/stable disease (p=0.007), and persistence of metastatic lymph nodes (p=0.004) versus group 1, respectively.

Conclusions This study showed that HPV status at diagnosis could be a relevant factor for clinical outcomes in locally advanced cervical cancer patients.

  • cervical cancer
  • radiotherapy
  • pathology

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • LCT and LPA contributed equally.

  • Contributors Conceptualization: LCT, LPA, Val, GZ, GS, and GF. Data curation: CF, FI, AP, NB, FC, VVar, MDN, and GM. Formal analysis: AP, MM, MV, SM, and RS. Funding acquisition: GS and GF. Investigation: LCT, LPA, CF, NB, FC, and VVar. Methodology: GF, MM, and GM. Project administration: LCT, GS, GF, and LPA. Resources: GZ, GS, GF, Val, and FC. Supervision: GZ, GS, GF, Val, and FC. Validation: GZ, GS, GF, Val, FC, LCT, and LPA. Roles/writing-original draft: LCT, LPA, FI, and CF. Writing-review and editing: GF, Val, GZ, GS, and FC. Garantor of the study: GF.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.