Cervical cancer screening with HPV testing in the Valcamonica (Italy) screening programme

Pasquale, Luigi; Rossi, Paolo Giorgi; Carozzi, Francesca; Pedretti, C; Ruggeri, C.; Scalvinoni, V; Cottini, M.; Tosini, A; Morana, C; Chiaramonte, M; Sacristani, MF; Cirelli, Richard; Chiudinelli, D; Piccolomini, Manuela; Marchione, Roberta; Romano, Lucio; Domenighini, Serena; Pieracci, G; Confortini, Massimo

doi:10.1177/0969141314561707

Cited by 18 publications

(27 citation statements)

References 27 publications

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“…As HPV positivity rates are strictly associated with the age of the target population, the local circulation of high‐risk HPV types (greatly variable across different countries), and the screening interval, our results cannot be directly compared with other data from the literature. Nonetheless, our figures are in line with another Italian pilot programme with the same age range and screening interval (8.7% at first screening; 3.9% at the second screening) . Moreover, the Pobascam trial also reported a reduction by about one‐quarter (from 4.5 to 3.3%) of HPV positivity at the second screening with a 5‐year interval …”

Section: Discussionsupporting

confidence: 90%

“…Moving from the first to the second screening, the colposcopy workload was more than halved (2.0 versus 4.4%). Thus, even if the workload generated by the HPV‐based protocol exceeds that of cytology‐based screening, this seems to be limited to the first round. This result needs to be confirmed for a 5‐year interval.…”

Section: Discussionmentioning

confidence: 99%

“…Nonetheless, our figures are in line with another Italian pilot programme with the same age range and screening interval (8.7% at first screening; 3.9% at the second screening). 21 Moreover, the Pobascam trial also reported a reduction by about one-quarter (from 4.5 to 3.3%) of HPV positivity at the second screening with a 5-year interval. 22 At the second screening, we observed a significant reduction of positivity at cytological triage (32.6 versus 38.5% at first screening); however, we are inclined to relate this result to the learning process that occurs when initiating a new activity.…”

Section: Main Findingsmentioning

confidence: 97%

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A 3‐year interval is too short for re‐screening women testing negative for human papillomavirus: a population‐based cohort study

Zorzi

Frayle

Rizzi

et al. 2017

BJOG

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Greater sensitivity, which lowers cancer incidence (Rocco et al. Lancet 2014), extended screening intervals and prophylactic vaccination provide the rationale for high-risk human papillo-mavirus (HR-HPV) testing to replace cytology as the primary test in cervical screening programmes both in the UK and internationally. Zorzi et al. report in BJOG, a timely cohort study from Italy of primary HPV cervical screening, concluding that following primary HPV screening, 3 years is too soon for a repeat screening round. Trials of HR-HPV testing have already demonstrated that the screening interval can safely be extended beyond 3 years (Kitchener et al. Eur J Cancer 2011;47:864-87), but 'real world' data are nonetheless relevant. The group of greatest interest is HR-HPV-positive women with negative cytology, which warrants early recall at 12 months to realise the added sensitivity of HPV screening. Clinical outcomes that matter most are: compliance with early recall, the positive predictive value (PPV) of additional colposcopy referral, the proportion of high-grade cervical intraepithelial neoplasia (CIN) detected at early recall, and the prevalence of HPV and high-grade CIN at the 3-year screening round, the latter serving as a surrogate of the safety of interval extension. These are all available from the Italian study, but two limitations, which affect the generalis-ability of the findings, should be noted. The first was the low prevalence of HR-HPV (6.3%), when compared with age-matched data of around twice that level in the ARTISTIC trial, which screened an urban UK population using the same assay(Kitchener et al. Br J Cancer 2006;95:56-61). This has a direct impact on both colposcopy referral and CIN detection. The second is that the use of a separate sample for conventional cytology, rather than reflex liquid-based cytology from the HPV sample, is suboptimal. Of those who screened as HPV-positive, 58% had negative cytology, which required 12 month recall. Encouragingly, over 80% attended early recall, of whom 42% had cleared HPV, the rest were referred to col-poscopy with detection of high-grade CIN in only 7.5%. These lesions amounted to an additional one-third over that found at initial screening, confirming inferior sensitivity of the baseline conventional cytology. At the 3-year round, the combined detection (baseline plus early recall) of high-grade CIN was only 0.1% of those screened (compared with 0.44% in the first round) and required almost 20 colposcopies for each high-grade CIN lesion, with just two CIN 3 lesions among 180 colposcopies, and over 21 000 women screened. This study certainly confirms the safety of extending the screening interval ; 5 years has already been determined for the Dutch and Australian programmes, and a similar interval will probably be used in the English Programme , with the potential for longer intervals in women over 50 years. The Italian study ignored partial genotyp-ing, as used in the ongoing English HPV pilot project, to detect HPV types 16/18 at early recall to achieve mo...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Main Findingsmentioning

confidence: 97%

See 1 more Smart Citation

A 3‐year interval is too short for re‐screening women testing negative for human papillomavirus: a population‐based cohort study

Zorzi

Frayle

Rizzi

et al. 2017

BJOG

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“…As reported by other Italian HPV-based screening pilot projects, we observed a higher participation in the programme compared with the historical participation rate in the Pap test screening program (Confortini et al , 2010; Zorzi et al , 2013b; Pasquale et al , 2015). The new test could be more appealing, making the public screening programme more competitive than the opportunistic screening in the private sector, which did not have the possibility to offer the HPV test at reasonable prices during the study period.…”

Section: Discussionsupporting

confidence: 77%

Screening women for cervical cancer carcinoma with a HPV mRNA test: first results from the Venice pilot program

Maggino

Sciarrone²,

Murer

et al. 2016

Br J Cancer

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Background:HPV DNA-based screening is more effective than a Pap test in preventing cervical cancer, but the test is less specific. New HPV tests have been proposed for primary screening. The HPV mRNA test showed a similar or slightly lower sensitivity than the HPV DNA tests but with a higher specificity. We report the results of an organised HPV mRNA-based screening pilot program in Venice, Italy.Methods:From October 2011 to May 2014, women aged 25–64 years were invited to undergo a HPV mRNA test (Aptima). Those testing positive underwent cytological triage. Women with positive cytology were referred to colposcopy, whereas those with negative cytology were referred to repeat the HPV mRNA test 1 year later. The results of the HPV mRNA test program were compared with both the local historical cytology-based program and with four neighbouring DNA HPV-based pilot projects.Results:Overall, 23 211 women underwent a HPV mRNA test. The age-standardised positivity rate was 7.0%, higher than in HPV DNA programs (6.8% relative rate (RR) 1.11, 95% confidence interval (CI) 1.05–1.17). The total colposcopy referral was 5.1%, double than with cytology (2.6% RR 2.02, 95% CI 1.82–2.25) but similar to the HPV DNA programs (4.8% RR 1.02; 95% CI 0.96–1.08). The cervical intraepithelial neoplasia grade 2+ detection rate with HPV mRNA was greater than in the HPV DNA programs at baseline (RR 1.50; 95% CI 1.19–1.88) and not significantly lower at the 1-year repeat (RR 0.70; 95% CI 0.40–1.16). The overall RR was 1.29 (95% CI 1.05–1.59), which was much higher than with cytology (detection rate 5.5‰ vs 2.1‰ RR 2.50, 95% CI 1.76–3.62).Conclusions:A screening programme based on the HPV mRNA obtained results similar to those observed with the HPV DNA test. In routine screening programmes, even a limited increase in HPV prevalence may conceal the advantage represented by the higher specificity of HPV mRNA.

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“…Longitudinal data from RCTs on persistently HPV16-positive women with no lesions detected should also be evaluated to define their longterm risk and best follow-up strategy before implementation of triage by partial genotyping. Finally, in the screening context, two additional caveats must be kept into consideration in the near future; namely, the different risk of precursor lesions in the first versus the subsequent hrHPV-based rounds, much lower in the second (16), and the screening strategy for vaccinated women, in whom lesions caused by types 16 and 18 will gradually disappear, and specific protocols will have to be designed.…”

mentioning

confidence: 99%

HPV Genotyping in the Prevention of Cervical Cancer—How and When Can It Be a Useful Marker?

Mistro

2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Persistent infection with high-risk human papillomavirus (hrHPV) types is the known cause of cervical cancer (1), a neoplasia suitable to effective primary and secondary prevention. For many decades, cervical cancer screening has been performed by cytology as the primary test, with significant reductions in cancer incidence (2), and, more recently, the use of hrHPV testing with cytology triage in large randomized controlled trials (RCT) has been demonstrated more effective than cytology in preventing invasive cervical cancer (3). The aim of screening is the prevention of cervical cancer through detection and excision of precursor lesions (namely, CIN2 and worse), and its effectiveness, besides primary test performance, depends on target population coverage and adherence to quality-controlled protocols; organized population-based screening is more cost-effective than opportunistic testing.HPV-based screening is more sensitive than cytology-based screening given the use of clinically validated tests for hrHPV types (4), in women 30 years and older, and triage of HPV-positive cases to counterbalance the 2.5% to 4% lower specificity (3). HPV infection is transient in the vast majority of the women (and particularly in those younger than 30-35 years of age) and only a minority harbor a persistent infection and have or are at risk of having a high-grade lesion (5). Spontaneous regression of CIN2 and, to a lesser extent, CIN3 lesions also occurs in a proportion of women and is more frequent in the youngest. Therefore, triage is necessary to select the women at higher risk of precancer who need immediate colposcopy, thus limiting excessive referral and overdiagnosis in women with transient and not (or less) clinically relevant HPV infections. Cytology is actually the most widely used test to triage hrHPV-positive women attending organized screening (6), but search for alternative (and less subjective) tests is advocated. Several studies, investigating p16 expression, HPV genotyping, HPV mRNA expression, and methylation of cellular and/or viral sequences as triage markers (used alone or in combination) have been published so far (7-12). These markers have been analyzed in terms of immediate or subsequent risk of CIN2 þ or CIN3 þ , sensitivity, specificity, positive predictive value, and cost-effectiveness (colposcopy referrals, overdiagnosis, and harms). These analyses have been performed on different populations (clinical settings or population-based screening), of different ages, cross-sectionally only or longitudinally. Overall, HPV16 has always been associated with the highest risk of CIN2 þ and CIN3 þ , with a three-tier ranking of the other hrHPV types; risks were highest in the first screening round, gradually decreasing over time but still persisting after more than 9 years (12). Moreover, an inverse relationship between sensitivity and specificity of the triage tests was always registered, and different combinations have been proposed. Indeed, the ideal triage test/strategy should allow selection of women at hig...

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Cervical cancer screening with HPV testing in the Valcamonica (Italy) screening programme

Abstract: HPV-based screening increases colposcopies at the first round, but also strongly increases the detection rate. At the second round, HPV prevalence was much lower and the detection rate also fell, corroborating the need for longer screening intervals in HPV-negative women.

Cited by 18 publications

References 27 publications

A 3‐year interval is too short for re‐screening women testing negative for human papillomavirus: a population‐based cohort study

A 3‐year interval is too short for re‐screening women testing negative for human papillomavirus: a population‐based cohort study

Screening women for cervical cancer carcinoma with a HPV mRNA test: first results from the Venice pilot program

HPV Genotyping in the Prevention of Cervical Cancer—How and When Can It Be a Useful Marker?

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