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Molecular pathways in vulvar squamous cell carcinoma: implications for target therapeutic strategies

  • Review – Cancer Research
  • Published:
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Abstract

Background

Additional prognostic factors and personalized therapeutic alternatives for vulvar squamous cell carcinoma (VSCC), especially for advanced stages with poor prognosis, are urgently needed.

Objectives

To review and assess literature regarding underlying molecular mechanisms of VSCC target therapeutic and prognostic approaches.

Methods

We performed a narrative literature review from the inception of the database up to January 2020 limited to English language, organizing knowledge in five main fields: extracellular and intracellular cell cycle deregulation, tumor immune microenvironment, tumor angiogenesis and hormones.

Results

EGFR immunohistochemical overexpression/gene amplification, representing early events in VSCC carcinogenesis, have been correlated with a worse prognosis and led to inclusion of erlotinib in cancer guidelines. p16 expression and HPV positivity are linked to a better prognosis, while p53 overexpression is linked to a worse prognosis; thus, biomarkers could help tailoring conventional treatment and follow-up. The implications of PD-L1 positivity in reference to HPV status and prognosis are still not clear, even though pembrolizumab is part of available systemic therapies. The role of tumor angiogenesis emerges through data on microvessel density, immunohistochemical VEGF staining and evaluation of serum VEGF concentrations. Few data exist on hormonal receptor expression, even though hormonal therapy showed great manageability.

Conclusions

We suggest adding p16, p53 and HPV status to routine hystopathological examination of vulvar biopsies or surgical specimens. Predictive biomarkers for anti-EGFR and anti-PD-1/PD-L1 drugs are needed. Enough preclinical data supporting anti-angiogenic target therapies in clinical trials are existing. Hormonal receptor expression deserves further investigation.

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Authors and Affiliations

  1. Dipartimento di Ginecologia e Ostetricia, Ginecologia Oncologica e Chirurgia Pelvica Mini-Invasiva, International School of Surgical Anatomy, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy

    Giulia Mantovani

  2. Unità di Ginecologia Oncologica, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy

    Simona Maria Fragomeni, Anna Fagotti, Giovanni Scambia & Giorgia Garganese

  3. Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Frediano Inzani & Gian Franco Zannoni

  4. Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy

    Anna Fagotti & Giovanni Scambia

  5. Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Scuola di Medicina e Chirurgia, Università degli studi di Napoli Federico II, Naples, Italy

    Luigi Della Corte

  6. Unità di Chirurgia Plastica, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Stefano Gentileschi

  7. Istituto di Clinica Chirurgica, Università Cattolica del Sacro Cuore, Rome, Italy

    Stefano Gentileschi

  8. Unità Operativa Complessa di Radioterapia, Dipartimento di Scienze Radiologiche, Radioterapiche ed Ematologiche, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy

    Luca Tagliaferri

  9. Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Rome, Italy

    Gian Franco Zannoni

  10. Gynecology and Breast Care Center, Mater Olbia Hospital, Olbia, Italy

    Giorgia Garganese

Authors
  1. Giulia Mantovani
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  2. Simona Maria Fragomeni
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  3. Frediano Inzani
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  4. Anna Fagotti
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  5. Luigi Della Corte
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  6. Stefano Gentileschi
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  7. Luca Tagliaferri
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  8. Gian Franco Zannoni
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  9. Giovanni Scambia
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  10. Giorgia Garganese
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Correspondence to Simona Maria Fragomeni.

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Giulia Mantovani, Fragomeni, S.M., Inzani, F. et al. Molecular pathways in vulvar squamous cell carcinoma: implications for target therapeutic strategies. J Cancer Res Clin Oncol 146, 1647–1658 (2020). https://doi.org/10.1007/s00432-020-03226-6

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