{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T04:31:40Z","timestamp":1773376300058,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>(1) Background\/Objectives: Human papillomavirus (HPV) testing is hypothesised to detect cervical intraepithelial neoplasia grade 3 (CIN3) earlier than cervical cytology, which could translate into several clinical benefits. This study aimed to confirm that HPV testing detects CIN3 lesions of smaller size (or linear extension) and to assess whether this is associated with a decreased risk of stromal microinvasion (\u22643 mm) (microinvasive or stage IA1 cervical carcinoma). (2) Methods: The study was conducted in a referral centre for cervical pathology in Italy. Eligible were 3744 patients aged 30\u201364 years who underwent local excision of the cervix between 1992 and 2021 and were diagnosed with CIN3, with or without microinvasion. Data were analysed using logistic and multinomial regression models. (3) Results: Overall, 1156 (30.9%) CIN3 cases were detected by the HPV test, and 2588 (69.1%) by cervical cytology. The lesion size was smaller in HPV test-detected CIN3 (median, 6 mm; interquartile range (IQR), 4\u20138 mm) than in cytology-detected CIN3 (median, 7 mm; IQR, 5\u20139 mm; p &lt; 0.001). HPV test-detected CIN3 was over 50% less likely to have a size &gt;6 mm combined with massive glandular crypt involvement. Stromal microinvasion occurred in 20\/1156 (1.7%) HPV test-detected lesions versus 87\/2588 (3.4%) cytology-detected lesions (p = 0.006), corresponding to an approximately 50% lower age-adjusted risk. The smaller size of HPV test-detected CIN3 and its lower degree of glandular crypt involvement interacted additively, rather than multiplicatively, in reducing the risk of stromal microinvasion. Over 46% of the association between detection mode and stromal microinvasion was explained by the size\/involvement composite variable. (4) Conclusions: HPV testing detects CIN3 lesions of smaller size than cervical cytology. HPV test-detected CIN3 has a lower risk of stromal microinvasion. This association is mediated to a substantial extent by the smaller lesion size and the less extensive glandular crypt involvement, which interact in an additive manner. These findings may have other important clinical implications. First, the prevalence of disease persistence after treatment may decrease. Second, smaller lesions are likely to be treated with more limited excisions. Third, this may contribute to a lower rate of preterm birth in subsequent pregnancies.<\/jats:p>","DOI":"10.3390\/cancers18030396","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:35:42Z","timestamp":1769513742000},"page":"396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human Papillomavirus Testing and Size of CIN3: Implications for the Risk of Microinvasive Cervical Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1573-3114","authenticated-orcid":false,"given":"Mario","family":"Preti","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences, St. Anna University Hospital, Via Ventimiglia 3, 10126 Torino, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2343-3346","authenticated-orcid":false,"given":"Annibale","family":"Biggeri","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Via Leonardo Loredan 18, 35131 Padua, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3016-1131","authenticated-orcid":false,"given":"Guglielmo","family":"Ronco","sequence":"additional","affiliation":[{"name":"Citt\u00e0 della Salute e della Scienza University Hospital, Corso Bramante 88, 10126 Turin, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-0735","authenticated-orcid":false,"given":"Maria","family":"Kyrgiou","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction\u2014Surgery and Cancer, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK"},{"name":"Imperial College Healthcare NHS Trust, Du Cane Road, London W12 0HS, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5294-9531","authenticated-orcid":false,"given":"Raffaella","family":"Rizzolo","sequence":"additional","affiliation":[{"name":"Citt\u00e0 della Salute e della Scienza University Hospital, Corso Bramante 88, 10126 Turin, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8965-4307","authenticated-orcid":false,"given":"Paola","family":"Armaroli","sequence":"additional","affiliation":[{"name":"Epidemiology and Screening Unit, Reference Centre for Epidemiology and Cancer Prevention (CPO), Citt\u00e0 della Salute e della Scienza University Hospital, Via Cavour 31, 10123 Turin, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3041-1201","authenticated-orcid":false,"given":"Niccol\u00f2","family":"Gallio","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, St. Anna University Hospital, Via Ventimiglia 3, 10126 Torino, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4221-4459","authenticated-orcid":false,"given":"Murat","family":"Gultekin","sequence":"additional","affiliation":[{"name":"Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Hacettepe University, Faculty of Medicine, Sihhiye, Ankara 06100, T\u00fcrkiye"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-6656","authenticated-orcid":false,"given":"Federica","family":"Zamagni","sequence":"additional","affiliation":[{"name":"Emilia-Romagna Cancer Registry, Romagna Cancer Institute, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Via Piero Maroncelli 40, 47014 Meldola, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7577-9088","authenticated-orcid":false,"given":"Silvano","family":"Costa","sequence":"additional","affiliation":[{"name":"Gynaecology Division, Villa Chiara Hospital, Via Porrettana 170, 40033 Casalecchio di Reno, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5335-6770","authenticated-orcid":false,"given":"Pedro","family":"Vieira-Baptista","sequence":"additional","affiliation":[{"name":"Department of Gynecology-Obstetrics and Pediatrics, Faculdade de Medicina da Universidade do Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"HPV and Vulvovaginal Pathology Unit, Hospital Lus\u00edadas Porto, Av. da Boavista 171, 4050-115 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8398-7557","authenticated-orcid":false,"given":"Fulvio","family":"Borella","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, St. Anna University Hospital, Via Ventimiglia 3, 10126 Torino, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0563-0071","authenticated-orcid":false,"given":"Stefano","family":"Cosma","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, St. Anna University Hospital, Via Ventimiglia 3, 10126 Torino, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5965-0721","authenticated-orcid":false,"given":"Luigia","family":"Macr\u00ec","sequence":"additional","affiliation":[{"name":"Pathology Unit, Citt\u00e0 della Salute e della Scienza University Hospital, Corso Bramante 88, 10126 Turin, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-5800","authenticated-orcid":false,"given":"Christine","family":"Bergeron","sequence":"additional","affiliation":[{"name":"CerbaPath, 30-32 Boulevard de Vaugirard, 75015 Paris, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0673-3347","authenticated-orcid":false,"given":"Silvia","family":"Mancini","sequence":"additional","affiliation":[{"name":"Emilia-Romagna Cancer Registry, Romagna Cancer Institute, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Via Piero Maroncelli 40, 47014 Meldola, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2167-9270","authenticated-orcid":false,"given":"Laura","family":"De Marco","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Unit, Reference Centre for Epidemiology and Cancer Prevention (CPO), Citt\u00e0 della Salute e della Scienza University Hospital, Corso Bramante 88, 10126 Turin, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3087-4549","authenticated-orcid":false,"given":"Daniele","family":"Tota","sequence":"additional","affiliation":[{"name":"Pathology Unit, Citt\u00e0 della Salute e della Scienza University Hospital, Corso Bramante 88, 10126 Turin, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6771-8119","authenticated-orcid":false,"given":"Lauro","family":"Bucchi","sequence":"additional","affiliation":[{"name":"Emilia-Romagna Cancer Registry, Romagna Cancer Institute, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Via Piero Maroncelli 40, 47014 Meldola, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S0140-6736(13)62218-7","article-title":"Efficacy of HPV-based screening for prevention of invasive cervical cancer: Follow-up of four European randomised controlled trials","volume":"383","author":"Ronco","year":"2014","journal-title":"Lancet"},{"key":"ref_2","first-page":"372","article-title":"Histopathologic extent of cervical intraepithelial neoplasia 3 lesions in the atypical squamous cells of undetermined significance low-grade squamous intraepithelial lesion triage study: Implications for subject safety and lead-time bias","volume":"12","author":"Sherman","year":"2003","journal-title":"Cancer Epidemiol. 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Sci., 20.","DOI":"10.3390\/ijms20092262"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/3\/396\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T05:23:18Z","timestamp":1769664198000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/3\/396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["cancers18030396"],"URL":"https:\/\/doi.org\/10.3390\/cancers18030396","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]}}}