Tissue genotyping of 37 in situ and invasive cervical cancer with a concomitant negative HC2 HPV DNA Test

Sarah Igidbashian, Maria Teresa Schettino, Sara Boveri, Massimo Barberis, Maria Teresa Sandri, Silvestro Carinelli, Maria Cannone, Mario Sideri

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: The rare occurrence of histology-proven cervical intraepithelial neoplasia grade 3 (CIN 3) or invasive cancer with a negative HC2 result is known. Tissue blocks of 37 cases of histology-diagnosed CIN 3+ with a concomitant negative HC2 test were genotyped to investigate the human papillomavirus (HPV) status within the lesion. METHODS: We considered 1,976 cervical excision specimens performed with concomitant HC2 test. Of these, 37 histology-confirmed CIN 3+ resulted HC2 negative. Thirty-three paraffin blocks, derived by the cervical excision, could be genotyped for high- (HR) and low-risk (LR) HPV genotypes. RESULTS: Detailed histology showed 30 CIN 3, 2 squamous cell invasive carcinomas, and 5 invasive adenocarcinomas. One specimen resulted not amplifiable at the genotyping. Twenty-two cases (68.7%) were positive for HR-HPV types, either in single (n = 17) or multiple HR-HPV infection (n = 5). Most of the HR-HPVs found were 16 or 18. Ten cases (31.3%) were negative for HR-HPV types; 5 of these were positive for probable HR-HPV types, not detectable with HC2 HR-probes, 1 was positive to LR-HPV types, while 1 had HPV-69/71. Three cases were negative for HPV DNA, either high or low risk. CONCLUSIONS: Of the rare cases of CIN 3+ lesions with concomitant negative HC2 test, 69% are true failures in HR-HPV detection. One third of HC2-negative CIN 3+ is related to the presence of other HPV genotypes not covered by the HC2 panel or to undetectable HPV in the lesion; both these rare occurrences were already described in large cancer series and partially explain the occurrence of HPV-negative CIN 3+.

Original languageEnglish
Pages (from-to)87-91
Number of pages5
JournalJournal of Lower Genital Tract Disease
Issue number1
Publication statusPublished - Jan 2014


  • cervical cancer
  • CIN 3
  • high-risk HPV
  • HPV-negative CIN 3+

ASJC Scopus subject areas

  • Obstetrics and Gynaecology


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