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Cited by 19Cervical Cancer and HPV ResearchWomen's cancer prevention and managementReproductive tract infections research

Comparison of HPV-positive triage strategies combining extended genotyping with cytology or p16/ki67 dual staining in the Italian NTCC2 study

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Benevolo, Maria, Ronco, Guglielmo, Mancuso, Pamela, Carozzi, Francesca, De Marco, Laura, Allia, Elena, Bisanzi, Simonetta, Rizzolo, Raffaella +59 more·2024·eBioMedicine
DOI 10.1016/j.ebiom.2024.105149PMC PMC11126882
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Abstract

BACKGROUND: Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping. METHODS: Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance. FINDINGS: Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting. INTERPRETATION: Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years. FUNDING: Italian Ministry of Health (grant number RF-2009-1536040). Hologic-Genprobe, Roche Diagnostics, and Becton & Dickinson provided financial and non-financial support.

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  • Extended genotyping to determine whom to treat based on risk has been shown to improve sensitivity for the detection of CIN 3+ and facilitate safe deferring of colposcopy if the HPV types are of lower carcinogenic potential (Group d).

    “Extended genotyping (inclusion of the next most carcinogenic types - Group 1c) to determine whom to treat based on risk has also been shown to improve sensitivity for the detection of CIN 3+ and facilitate safe deferring of colposcopy if the HPV types are of lower carcinogenic potential (Group d).51 52”

    From Protocol for a cervical screening implementation trial comparing two approaches for delivering HPV self-collection in low-resource settings in India: a type 3 hybrid cluster randomised controlled trial (SHE-CAN) (2025) · cites this paper as [52]

    Table 3 (Results, page unavailable) shows that one extended-genotyping strategy detected a greater proportion of CIN3 immediately than a partial-genotyping strategy. The Discussion (Main findings, page unavailable) supports deferring colposcopy for a low-risk group, but only when genotype is combined with negative cytology or dual staining; the study evaluates triage and retesting, not whom to treat directly. (LLM, conf=0.85)

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Authors
Benevolo, M., Ronco, G., Mancuso, P., Carozzi, F., De Marco, L., Allia, E., Bisanzi, S., Rizzolo, R., Gustinucci, D., Del Mistro, A., Frayle, H., Confortini, M., Viti, J., Iossa, A., Cesarini, E., Bulletti, S., Passamonti, B., Gori, S., Toniolo, L., Bonvicini, L., Venturelli, F., Wentzensen, N., Giorgi Rossi, P., Barca, A., Quadrino, F., Benevolo, M., Rollo, F., Rossi, P. G., Mancuso, P., Venturelli, F., Bonvicini, L., Carlinfante, G., Rubino, T., Carozzi, F. M., Bisanzi, S., Iossa, A., Sani, C., Viti, J., Baldini, A., Pompeo, G., Mongia, A., Fantacci, G., Puliti, D., Di Pierro, C., Confortini, M., Ronco, G., De Marco, L., Allia, E., Rizzolo, R., Macrì, L., Pusiol, T., Barbareschi, M., Bragantini, E., Passamonti, B., Gustinucci, D., Cesarini, E., Bulletti, S., Penon, G., Toniolo, L., Marchi, N., Del Mistro, A., Frayle, H., Gori, S., Zorzi, M., Narne, E., Turrin, A., & Giorgi Rossi, P.
Affiliations
  • National Cancer Institute (US)
  • Azienda Sanitaria Unità Locale di Reggio Emilia (IT)
  • University of Perugia (IT)
ORCID
Venue
eBioMedicine
Publisher
Elsevier BV
Published
2024-06
Volume
104
Pages
105149
ISSN
2352-3964 (ISSN-L)
DOI
10.1016/j.ebiom.2024.105149
PMC
PMC11126882
OpenAlex
W4397019773
Cited by
19
References
45
Citations by year
2026: 10 · 2025: 9
FWCI
5.80
Type
journal article
Language
en
Open access
Licence
Locations
  • EBioMedicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Institutional Research Information System (Università degli Studi di Trento) (submittedVersion, cc-by-nc-nd)
Funders
Ministero della Salute (RF-2009-1536040)
Topics
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Women's cancer prevention and management
  • Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
Keywords
cervical cytology, cervical intraepithelial neoplasia grade 3, HPV genotypes, colposcopy referral, cervical cancer screening
MeSH terms
Cytology, Adult, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms, Colposcopy, Cytodiagnosis, DNA, Viral, Female, Genotype, Humans, Italy, Middle Aged, Retrospective Studies, Staining and Labeling, Triage, Ki-67 Antigen, Cyclin-Dependent Kinase Inhibitor p16, Papillomaviridae, Papillomavirus Infections, Early Detection of Cancer, Genotyping Techniques

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