P16 and hpv genotype significance in hpv-associated cervical cancer-a large cohort of two tertiary referral centers

Sara da Mata, Joana Ferreira, Inmaculada Nicolás, Susana Esteves, Gonçalo Esteves, Sofia Lérias, Fernanda Silva, Adela Saco, Daniela Cochicho, Mário Cunha, Marta Del Pino, Jaume Ordi, Ana Félix

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The expression of p16 is a good surrogate of human papillomavirus (HPV) infection in HPV-associated cancers. The significance of p16 expression, HPV genotype and genera in the outcome of patients with HPV-associated cervical cancer (CC) is unclear. Our aim is to ascertain the prognostic significance of these factors. Data from 348 patients (median age: 47.5 years old) with CC, diagnosed in two referral centers, were retrospectively collected. Advanced disease (FIGO2018 IB2-IV) was present in 68% of patients. A single HPV genotype was identified in 82.8% of patients. The most common HPVs were HPV16 (69%) and HPV18 (14%). HPV genera reflected this distribution. HPV16 tumors presented at an earlier stage. P16 was negative in 18 cases (5.2%), 83.3% of which were squamous cell carcinomas. These cases occurred in older patients who tended to have advanced disease. In the univariate analysis, HPV16 (HR: 0.58; p = 0.0198), α-9 genera (HR: 0.37; p = 0.0106) and p16 overexpression (HR: 0.54; p = 0.032) were associated with better survival. HPV16 (HR: 0.63; p = 0.0174) and α-9 genera (HR: 0.57; p = 0.0286) were associated with less relapse. In the multivariate analysis, only the International Federation of Gynecology and Obstetrics (FIGO) stage retained an independent prognostic value. HPV16, α-9 genera and p16 overexpression were associated with better survival, although not as independent prognostic factors. Patients with p16-nega-tive HPV-associated CC were older, presented with advanced disease and had worse prognosis.

Original languageEnglish
Article number2294
Pages (from-to)1-13
Number of pages13
JournalInternational Journal of Molecular Sciences
Issue number5
Publication statusPublished - 1 Mar 2021


  • Cervical cancer
  • HPV
  • P16 expression


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