Five‐year risk of <scp>CIN</scp>3 after short‐term <scp>HPV</scp>‐<scp>DNA</scp> negativity in cytology‐negative women: a population‐based cohort study

Mistro, Annarosa Del; Rossi, Paolo Giorgi; Frayle, Helena; Pasquale, Luigi; Campari, Cinzia; Ronco, Guglielmo; Zorzi, Manuel

doi:10.1111/1471-0528.15893

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…Among those who attended their routine recall in three years (which took place four or five years after the HPV positive primary screen, depending on when the negative early recall test was recorded), 5.4 per 1000 women had CIN3+. Consistent with data from earlier small studies, 26 27 this incidence was about three times higher than after an HPV negative screen. The risk was in fact similar to that among 260 266 women younger than 50 years who had negative cytology and were screened again after a three year routine recall (4.5 with CIN3+ per 1000 screened in the second round, table 2 ).…”

Section: Discussionsupporting

confidence: 91%

Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data

Cuschieri

Mathews

Pesola

et al. 2022

BMJ

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Objectives To provide updated evidence about the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and cervical cancer after a negative human papillomavirus (HPV) test in primary cervical screening, by age group and test assay. Design Observational study. Setting Real world data from the English HPV screening pilot’s first and second rounds (2013-16, follow-up to end of 2019). Participants 1 341 584 women. Interventions Cervical screening with HPV testing or liquid based cytological testing (cytology or smear tests). Women screened with cytology were referred to colposcopy after high grade cytological abnormalities or after borderline or low grade abnormalities combined with a positive HPV triage test. Women screened with HPV testing who were positive were referred at baseline if their cytology triage test showed at least borderline abnormalities or after a retest (early recall) at 12 and 24 months if they had persistent abnormalities. Main outcome measures Detection of CIN3+ and cervical cancer after a negative HPV test. Results For women younger than 50 years, second round detection of CIN3+ in this study was significantly lower after a negative HPV screen in the first round than after cytology testing (1.21/1000 v 4.52/1000 women screened, adjusted odds ratio 0.26, 95% confidence interval 0.23 to 0.30), as was the risk of interval cervical cancer (1.31/100 000 v 2.90/100 000 woman years, adjusted hazard ratio 0.44, 0.23 to 0.84). Risk of an incident CIN3+ detected at the second screening round in the pilot five years after a negative HPV test was even lower in women older than 50 years, than in three years in women younger than 50 years (0.57/1000 v 1.21/1000 women screened, adjusted odds ratio 0.46, 0.27 to 0.79). Women with negative HPV tests at early recall after a positive HPV screening test without cytological abnormalities had a higher detection rate of CIN3+ at the second routine recall than women who initially tested HPV negative (5.39/1000 v 1.21/1000 women screened, adjusted odds ratio 3.27, 95% confidence interval 2.21 to 4.84). Detection after a negative result on a clinically validated APTIMA mRNA HPV test was similar to that after clinically validated cobas and RealTime DNA tests (for CIN3+ at the second round 1.32/1000 v 1.14/1000 women screened, adjusted odds ratio 1.05, 0.73 to 1.50). Conclusions These data support an extension of the screening intervals, regardless of the test assay used: to five years after a negative HPV test in women aged 25-49 years, and even longer for women aged 50 years and older. The screening interval for HPV positive women who have negative HPV tests at early recall should be kept at three years.

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Section: Discussionsupporting

confidence: 91%

Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data

Cuschieri

Mathews

Pesola

et al. 2022

BMJ

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“…In this study we evaluated partial HPV16/18 genotyping as a triage biomarker for high‐risk HPV‐positive women identified within organised HPV cervical screening, in order to devise new strategies to improve its efficacy. This is especially important for the management of HPV‐positive women with negative cytology at baseline, which is particularly challenging 30 …”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of partial HPV16/18 genotyping in stratifying HPV‐positive women attending routine cervical cancer screening: a population‐based cohort study

Gori

Battagello

Gustinucci³

et al. 2021

BJOG

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Objective To evaluate partial HPV16/18 genotyping as a possible biomarker to select women attending HPV‐based cervical cancer screening at higher risk to be referred to colposcopy. Design Population‐based cohort study. Setting Organised cervical cancer screening programmes (Italy). Population Women with high‐risk HPV infection (period: 2015–2019). Methods We analysed the association between partial HPV16/18 genotyping, cytology triage and histologically confirmed diagnosis of high‐grade cervical intraepithelial neoplasia (CIN3+) lesions. Main outcome measures Detection rate (DR) and positive predictive value (PPV) for histologically confirmed CIN3+ (any episode in the 2 years after baseline); sensitivity for CIN3+ and number of colposcopies needed for lesion detection. Results The study included 145 437 women screened with HPV testing by the clinically validated COBAS 4800 HPV assay (Roche). Overall, 9601 (6.6%) women were HPV+ at baseline; HPV16 and HPV18 were present in 1865 and 594 samples, respectively. The cumulative (baseline plus 1‐year repeat) cytology positivity was 42.8% and high‐grade cytology was significantly higher (P < 0.0001) among women with HPV16 infection at baseline (15.2%). The cumulative CIN3+ DR for women with HPV16, HPV18 and other HPV‐type infections was 9.8%, 3.4% and 1.8%, respectively. Conclusions Partial HPV16 genotyping may play a role in triage, whereas HPV18 seems to behave much more similarly to the other HPV types and does not provide additional stratification. HPV16 genotyping combined with high‐grade cytology can be envisaged as a triage biomarker in cervical screening to maximise CIN3+ detection while minimising colposcopy at baseline or 1‐year repeat. Tweetable abstract HPV16 genotyping combined with high‐grade cytology can be used as triage biomarker for CIN3+ in HPV‐positive women.

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“…Another point worth noting is that among the 24 cases with HPV-DNA positivity in the Test group, only 10 cases were positive by HPV RNAscope analysis, and the positive rate was 41.7%. We speculate that the results are mainly related to transient HPV infection because the virus is then cleared by the body's own immune system [39][40][41]. The virus is not involved in the cervical surface epithelium, so we cannot observe the presence of HPV virus particles in HPV RNAscope.…”

Section: Discussionmentioning

confidence: 99%

CIN Grades Possessing Different HPV RNA Location Patterns and RNAscope are Helpful Tools for Distinguishing Squamous Intraepithelial Lesions in Difficult Cervical Cases

Chen

Zhang

et al. 2022

Preprint

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Background and objectives: The precise grading and characterization of cervical intraepithelial neoplasia (CIN) has been the focus of pathologists for a long time. This study aimed to explore known strategies for the grading of CINs.Methods: After routine H&E review, 85 lesions graded CIN 1, 2, or 3 were investigated primarily by HPV RNAscope to detect HR-HPV and LR-HPV, in combination with an HPV-DNA test and P16/Ki67 immunohistochemistry (IHC). Then, the 85 cases were divided into a control group (49 cases) and a test group (36 cases). The former consisted of cases with consistency between morphology, HPV DNA detection and P16/Ki67 IHC. We used them to evaluate HPV RNA distribution patterns in CINs of different grades. The latter were ambiguous cases in which pathologists could not confirm the diagnosis because of inconsistencies between morphology, HPV DNA detection and P16/Ki67 IHC. We reassessed them by comparison to the pattern in the control group.Results: The expression patterns of HPV mRNA signals were different in different CIN lesions. LSIL/CIN1 lesions were mostly expressed in superficial epithelium with diffuse clustered nuclear or cytoplasmic staining; HSIL/CIN2 were characterised by nuclear/cytoplasmic punctate or diffuse cluster nuclear staining in the mid-surface layer, and scattered nuclear/cytoplasmic punctate staining in basal and parabasal cells; whereas HSIL/CIN3 showed full-thickness nucleus/cytoplasmic scattered staining with a punctate pattern. According to the staining pattern, we corrected the diagnosis of 22 cases (22/36, 61.1%). Conclusion: Because of its distinct location pattern, HPV RNAscope has obvious advantages over the HPV-DNA test, and combined with P16/Ki67 IHC, it can help pathologists correctly grade CIN. In addition, it can effectively discriminate true CIN from normal or CIN mimic lesions, such as immature squamous metaplasia, atrophy, and inflammatory/reactive changes. Therefore, HPV RNAscope is a valuable auxiliary diagnostic test to avoid the overtreatment and undertreatment of CIN lesions.

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Five‐year risk of CIN3 after short‐term HPV‐DNA negativity in cytology‐negative women: a population‐based cohort study

Cited by 5 publications

References 21 publications

Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data

Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data

Clinical relevance of partial HPV16/18 genotyping in stratifying HPV‐positive women attending routine cervical cancer screening: a population‐based cohort study

CIN Grades Possessing Different HPV RNA Location Patterns and RNAscope are Helpful Tools for Distinguishing Squamous Intraepithelial Lesions in Difficult Cervical Cases

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