Informed cytology for triaging HPV-positive women: Substudy nested in the NTCC randomized controlled trial

Christine Bergeron, Paolo Giorgi-Rossi, Frederic Cas, Maria Luisa Schiboni, Bruno Ghiringhello, Paolo Dalla Palma, Daria Minucci, Stefano Rosso, Manuel Zorzi, Carlo Naldoni, Nereo Segnan, Massimo Confortini, Guglielmo Ronco

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background: Human papillomavirus (HPV)-based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status. Methods: Women age 25 to 60 years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV testing with cytology were referred to colposcopy if HPV positive and, if no cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV negativity. Cytological slides taken at the first colposcopy were retrieved and independently interpreted by an external laboratory, which was only aware of patients' HPV positivity. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were computed for histologically proven CIN2+ with HPV status-informed cytology for women with a determination of atypical squamous cells of undetermined significance (ASCUS) or more severe. All statistical tests were two-sided. Results: Among HPV-positive women, informed cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of 85.6% (95% confidence interval [CI] = 76.6 to 92.1), 65.9% (95% CI = 63.1 to 68.6), 16.2% (95% CI = 13.0 to 19.8), and 1.7 (95% CI = 0.9 to 2.8), respectively. Cytology was also associated with subsequent risk of newly diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs blind cytology obtained by referring to colposcopy and following up only HPV positive women who had HPV status-informed cytology greater than or equal to ASCUS was 1.58 (95% CI = 1.22 to 2.01), while the corresponding relative referral to colposcopy was 0.95 (95% CI = 0.86 to 1.04). Conclusions: Cytology informed of HPV positivity is more sensitive than blind cytology and could allow longer intervals before retesting HPV-positive, cytology-negative women.

Original languageEnglish
Article numberdju423
JournalJournal of the National Cancer Institute
Volume107
Issue number2
DOIs
Publication statusPublished - Feb 1 2015

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Uterine Cervical Neoplasms
Cell Biology
Randomized Controlled Trials
Technology
Colposcopy
Confidence Intervals
Triage
Sensitivity and Specificity
Cervical Intraepithelial Neoplasia
Referral and Consultation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Informed cytology for triaging HPV-positive women : Substudy nested in the NTCC randomized controlled trial. / Bergeron, Christine; Giorgi-Rossi, Paolo; Cas, Frederic; Schiboni, Maria Luisa; Ghiringhello, Bruno; Palma, Paolo Dalla; Minucci, Daria; Rosso, Stefano; Zorzi, Manuel; Naldoni, Carlo; Segnan, Nereo; Confortini, Massimo; Ronco, Guglielmo.

In: Journal of the National Cancer Institute, Vol. 107, No. 2, dju423, 01.02.2015.

Research output: Contribution to journalArticle

Bergeron, C, Giorgi-Rossi, P, Cas, F, Schiboni, ML, Ghiringhello, B, Palma, PD, Minucci, D, Rosso, S, Zorzi, M, Naldoni, C, Segnan, N, Confortini, M & Ronco, G 2015, 'Informed cytology for triaging HPV-positive women: Substudy nested in the NTCC randomized controlled trial', Journal of the National Cancer Institute, vol. 107, no. 2, dju423. https://doi.org/10.1093/jnci/dju423
Bergeron, Christine ; Giorgi-Rossi, Paolo ; Cas, Frederic ; Schiboni, Maria Luisa ; Ghiringhello, Bruno ; Palma, Paolo Dalla ; Minucci, Daria ; Rosso, Stefano ; Zorzi, Manuel ; Naldoni, Carlo ; Segnan, Nereo ; Confortini, Massimo ; Ronco, Guglielmo. / Informed cytology for triaging HPV-positive women : Substudy nested in the NTCC randomized controlled trial. In: Journal of the National Cancer Institute. 2015 ; Vol. 107, No. 2.
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abstract = "Background: Human papillomavirus (HPV)-based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status. Methods: Women age 25 to 60 years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV testing with cytology were referred to colposcopy if HPV positive and, if no cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV negativity. Cytological slides taken at the first colposcopy were retrieved and independently interpreted by an external laboratory, which was only aware of patients' HPV positivity. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were computed for histologically proven CIN2+ with HPV status-informed cytology for women with a determination of atypical squamous cells of undetermined significance (ASCUS) or more severe. All statistical tests were two-sided. Results: Among HPV-positive women, informed cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of 85.6{\%} (95{\%} confidence interval [CI] = 76.6 to 92.1), 65.9{\%} (95{\%} CI = 63.1 to 68.6), 16.2{\%} (95{\%} CI = 13.0 to 19.8), and 1.7 (95{\%} CI = 0.9 to 2.8), respectively. Cytology was also associated with subsequent risk of newly diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs blind cytology obtained by referring to colposcopy and following up only HPV positive women who had HPV status-informed cytology greater than or equal to ASCUS was 1.58 (95{\%} CI = 1.22 to 2.01), while the corresponding relative referral to colposcopy was 0.95 (95{\%} CI = 0.86 to 1.04). Conclusions: Cytology informed of HPV positivity is more sensitive than blind cytology and could allow longer intervals before retesting HPV-positive, cytology-negative women.",
author = "Christine Bergeron and Paolo Giorgi-Rossi and Frederic Cas and Schiboni, {Maria Luisa} and Bruno Ghiringhello and Palma, {Paolo Dalla} and Daria Minucci and Stefano Rosso and Manuel Zorzi and Carlo Naldoni and Nereo Segnan and Massimo Confortini and Guglielmo Ronco",
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AU - Bergeron, Christine

AU - Giorgi-Rossi, Paolo

AU - Cas, Frederic

AU - Schiboni, Maria Luisa

AU - Ghiringhello, Bruno

AU - Palma, Paolo Dalla

AU - Minucci, Daria

AU - Rosso, Stefano

AU - Zorzi, Manuel

AU - Naldoni, Carlo

AU - Segnan, Nereo

AU - Confortini, Massimo

AU - Ronco, Guglielmo

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N2 - Background: Human papillomavirus (HPV)-based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status. Methods: Women age 25 to 60 years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV testing with cytology were referred to colposcopy if HPV positive and, if no cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV negativity. Cytological slides taken at the first colposcopy were retrieved and independently interpreted by an external laboratory, which was only aware of patients' HPV positivity. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were computed for histologically proven CIN2+ with HPV status-informed cytology for women with a determination of atypical squamous cells of undetermined significance (ASCUS) or more severe. All statistical tests were two-sided. Results: Among HPV-positive women, informed cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of 85.6% (95% confidence interval [CI] = 76.6 to 92.1), 65.9% (95% CI = 63.1 to 68.6), 16.2% (95% CI = 13.0 to 19.8), and 1.7 (95% CI = 0.9 to 2.8), respectively. Cytology was also associated with subsequent risk of newly diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs blind cytology obtained by referring to colposcopy and following up only HPV positive women who had HPV status-informed cytology greater than or equal to ASCUS was 1.58 (95% CI = 1.22 to 2.01), while the corresponding relative referral to colposcopy was 0.95 (95% CI = 0.86 to 1.04). Conclusions: Cytology informed of HPV positivity is more sensitive than blind cytology and could allow longer intervals before retesting HPV-positive, cytology-negative women.

AB - Background: Human papillomavirus (HPV)-based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status. Methods: Women age 25 to 60 years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV testing with cytology were referred to colposcopy if HPV positive and, if no cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV negativity. Cytological slides taken at the first colposcopy were retrieved and independently interpreted by an external laboratory, which was only aware of patients' HPV positivity. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were computed for histologically proven CIN2+ with HPV status-informed cytology for women with a determination of atypical squamous cells of undetermined significance (ASCUS) or more severe. All statistical tests were two-sided. Results: Among HPV-positive women, informed cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of 85.6% (95% confidence interval [CI] = 76.6 to 92.1), 65.9% (95% CI = 63.1 to 68.6), 16.2% (95% CI = 13.0 to 19.8), and 1.7 (95% CI = 0.9 to 2.8), respectively. Cytology was also associated with subsequent risk of newly diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs blind cytology obtained by referring to colposcopy and following up only HPV positive women who had HPV status-informed cytology greater than or equal to ASCUS was 1.58 (95% CI = 1.22 to 2.01), while the corresponding relative referral to colposcopy was 0.95 (95% CI = 0.86 to 1.04). Conclusions: Cytology informed of HPV positivity is more sensitive than blind cytology and could allow longer intervals before retesting HPV-positive, cytology-negative women.

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