Human papillomavirus testing and liquid-based cytology: Results at recruitment from the new technologies for cervical cancer randomized controlled trial

Guglielmo Ronco, Nereo Segnan, Paolo Giorgi-Rossi, Marco Zappa, Gian Piero Casadei, Francesca Carozzi, Paolo Dalla Palma, Annarosa Del Mistro, Stefania Folicaldi, Anna Gillio-Tos, Gaetano Nardo, Carlo Naldoni, Patrizia Schincaglia, Manuel Zorzi, Massimo Confortini, Jack Cuzick, R. Rizzolo, D. Mari, L. De Marco, B. GhiringhelloF. Parisio, R. Volante, E. Berardengo, A. Andrion, S. Coverlizza, S. Taraglio, M. G. Accinellli, E. Polla, A. Pojer, S. Girlando, D. Aldovini, M. Vettorazzi, D. Minucci, M. Matteucci, L. Onnis, E. Insacco, M. Lestani, A. Vignato, M. Manfredi, P. Pierotti, G. Collina, M. Serafini, C. Sintoni, M. Aldi, A. Bondi, G. Galanti, A. Iossa, S. Ciatto, M. P. Cariaggi, S. Cecchini, C. Sani, G. L. Taddie, S. Brezzi, P. Raggi, E. Gomes, A. Pellegrini, M. L. Schiboni

Research output: Contribution to journalArticle

248 Citations (Scopus)

Abstract

Background: Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results. Methods: In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16 658) were screened using conventional cytology, and women in the experimental arm (n = 16 706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (≥1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated. Results: The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at ≥1 pg/mL and at ≥2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82). Conclusions: HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.

Original languageEnglish
Pages (from-to)765-774
Number of pages10
JournalJournal of the National Cancer Institute
Volume98
Issue number11
DOIs
Publication statusPublished - Jun 7 2006

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Uterine Cervical Neoplasms
Cell Biology
Randomized Controlled Trials
Technology
Confidence Intervals
Cervical Intraepithelial Neoplasia
Referral and Consultation
Colposcopy
Early Detection of Cancer
Sensitivity and Specificity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Human papillomavirus testing and liquid-based cytology : Results at recruitment from the new technologies for cervical cancer randomized controlled trial. / Ronco, Guglielmo; Segnan, Nereo; Giorgi-Rossi, Paolo; Zappa, Marco; Casadei, Gian Piero; Carozzi, Francesca; Palma, Paolo Dalla; Del Mistro, Annarosa; Folicaldi, Stefania; Gillio-Tos, Anna; Nardo, Gaetano; Naldoni, Carlo; Schincaglia, Patrizia; Zorzi, Manuel; Confortini, Massimo; Cuzick, Jack; Rizzolo, R.; Mari, D.; De Marco, L.; Ghiringhello, B.; Parisio, F.; Volante, R.; Berardengo, E.; Andrion, A.; Coverlizza, S.; Taraglio, S.; Accinellli, M. G.; Polla, E.; Pojer, A.; Girlando, S.; Aldovini, D.; Vettorazzi, M.; Minucci, D.; Matteucci, M.; Onnis, L.; Insacco, E.; Lestani, M.; Vignato, A.; Manfredi, M.; Pierotti, P.; Collina, G.; Serafini, M.; Sintoni, C.; Aldi, M.; Bondi, A.; Galanti, G.; Iossa, A.; Ciatto, S.; Cariaggi, M. P.; Cecchini, S.; Sani, C.; Taddie, G. L.; Brezzi, S.; Raggi, P.; Gomes, E.; Pellegrini, A.; Schiboni, M. L.

In: Journal of the National Cancer Institute, Vol. 98, No. 11, 07.06.2006, p. 765-774.

Research output: Contribution to journalArticle

Ronco, G, Segnan, N, Giorgi-Rossi, P, Zappa, M, Casadei, GP, Carozzi, F, Palma, PD, Del Mistro, A, Folicaldi, S, Gillio-Tos, A, Nardo, G, Naldoni, C, Schincaglia, P, Zorzi, M, Confortini, M, Cuzick, J, Rizzolo, R, Mari, D, De Marco, L, Ghiringhello, B, Parisio, F, Volante, R, Berardengo, E, Andrion, A, Coverlizza, S, Taraglio, S, Accinellli, MG, Polla, E, Pojer, A, Girlando, S, Aldovini, D, Vettorazzi, M, Minucci, D, Matteucci, M, Onnis, L, Insacco, E, Lestani, M, Vignato, A, Manfredi, M, Pierotti, P, Collina, G, Serafini, M, Sintoni, C, Aldi, M, Bondi, A, Galanti, G, Iossa, A, Ciatto, S, Cariaggi, MP, Cecchini, S, Sani, C, Taddie, GL, Brezzi, S, Raggi, P, Gomes, E, Pellegrini, A & Schiboni, ML 2006, 'Human papillomavirus testing and liquid-based cytology: Results at recruitment from the new technologies for cervical cancer randomized controlled trial', Journal of the National Cancer Institute, vol. 98, no. 11, pp. 765-774. https://doi.org/10.1093/jnci/djj209
Ronco, Guglielmo ; Segnan, Nereo ; Giorgi-Rossi, Paolo ; Zappa, Marco ; Casadei, Gian Piero ; Carozzi, Francesca ; Palma, Paolo Dalla ; Del Mistro, Annarosa ; Folicaldi, Stefania ; Gillio-Tos, Anna ; Nardo, Gaetano ; Naldoni, Carlo ; Schincaglia, Patrizia ; Zorzi, Manuel ; Confortini, Massimo ; Cuzick, Jack ; Rizzolo, R. ; Mari, D. ; De Marco, L. ; Ghiringhello, B. ; Parisio, F. ; Volante, R. ; Berardengo, E. ; Andrion, A. ; Coverlizza, S. ; Taraglio, S. ; Accinellli, M. G. ; Polla, E. ; Pojer, A. ; Girlando, S. ; Aldovini, D. ; Vettorazzi, M. ; Minucci, D. ; Matteucci, M. ; Onnis, L. ; Insacco, E. ; Lestani, M. ; Vignato, A. ; Manfredi, M. ; Pierotti, P. ; Collina, G. ; Serafini, M. ; Sintoni, C. ; Aldi, M. ; Bondi, A. ; Galanti, G. ; Iossa, A. ; Ciatto, S. ; Cariaggi, M. P. ; Cecchini, S. ; Sani, C. ; Taddie, G. L. ; Brezzi, S. ; Raggi, P. ; Gomes, E. ; Pellegrini, A. ; Schiboni, M. L. / Human papillomavirus testing and liquid-based cytology : Results at recruitment from the new technologies for cervical cancer randomized controlled trial. In: Journal of the National Cancer Institute. 2006 ; Vol. 98, No. 11. pp. 765-774.
@article{295bb13ad2284aee95e39a1031c9e0ae,
title = "Human papillomavirus testing and liquid-based cytology: Results at recruitment from the new technologies for cervical cancer randomized controlled trial",
abstract = "Background: Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results. Methods: In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16 658) were screened using conventional cytology, and women in the experimental arm (n = 16 706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (≥1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated. Results: The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95{\%} confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95{\%} CI = 0.23 to 0.66). With HPV testing alone at ≥1 pg/mL and at ≥2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95{\%} CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95{\%} CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95{\%} CI = 0.33 to 0.98 and relative PPV = 0.75, 95{\%} CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95{\%} CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95{\%} CI = 0.39 to 0.82). Conclusions: HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.",
author = "Guglielmo Ronco and Nereo Segnan and Paolo Giorgi-Rossi and Marco Zappa and Casadei, {Gian Piero} and Francesca Carozzi and Palma, {Paolo Dalla} and {Del Mistro}, Annarosa and Stefania Folicaldi and Anna Gillio-Tos and Gaetano Nardo and Carlo Naldoni and Patrizia Schincaglia and Manuel Zorzi and Massimo Confortini and Jack Cuzick and R. Rizzolo and D. Mari and {De Marco}, L. and B. Ghiringhello and F. Parisio and R. Volante and E. Berardengo and A. Andrion and S. Coverlizza and S. Taraglio and Accinellli, {M. G.} and E. Polla and A. Pojer and S. Girlando and D. Aldovini and M. Vettorazzi and D. Minucci and M. Matteucci and L. Onnis and E. Insacco and M. Lestani and A. Vignato and M. Manfredi and P. Pierotti and G. Collina and M. Serafini and C. Sintoni and M. Aldi and A. Bondi and G. Galanti and A. Iossa and S. Ciatto and Cariaggi, {M. P.} and S. Cecchini and C. Sani and Taddie, {G. L.} and S. Brezzi and P. Raggi and E. Gomes and A. Pellegrini and Schiboni, {M. L.}",
year = "2006",
month = "6",
day = "7",
doi = "10.1093/jnci/djj209",
language = "English",
volume = "98",
pages = "765--774",
journal = "Journal of the National Cancer Institute",
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TY - JOUR

T1 - Human papillomavirus testing and liquid-based cytology

T2 - Results at recruitment from the new technologies for cervical cancer randomized controlled trial

AU - Ronco, Guglielmo

AU - Segnan, Nereo

AU - Giorgi-Rossi, Paolo

AU - Zappa, Marco

AU - Casadei, Gian Piero

AU - Carozzi, Francesca

AU - Palma, Paolo Dalla

AU - Del Mistro, Annarosa

AU - Folicaldi, Stefania

AU - Gillio-Tos, Anna

AU - Nardo, Gaetano

AU - Naldoni, Carlo

AU - Schincaglia, Patrizia

AU - Zorzi, Manuel

AU - Confortini, Massimo

AU - Cuzick, Jack

AU - Rizzolo, R.

AU - Mari, D.

AU - De Marco, L.

AU - Ghiringhello, B.

AU - Parisio, F.

AU - Volante, R.

AU - Berardengo, E.

AU - Andrion, A.

AU - Coverlizza, S.

AU - Taraglio, S.

AU - Accinellli, M. G.

AU - Polla, E.

AU - Pojer, A.

AU - Girlando, S.

AU - Aldovini, D.

AU - Vettorazzi, M.

AU - Minucci, D.

AU - Matteucci, M.

AU - Onnis, L.

AU - Insacco, E.

AU - Lestani, M.

AU - Vignato, A.

AU - Manfredi, M.

AU - Pierotti, P.

AU - Collina, G.

AU - Serafini, M.

AU - Sintoni, C.

AU - Aldi, M.

AU - Bondi, A.

AU - Galanti, G.

AU - Iossa, A.

AU - Ciatto, S.

AU - Cariaggi, M. P.

AU - Cecchini, S.

AU - Sani, C.

AU - Taddie, G. L.

AU - Brezzi, S.

AU - Raggi, P.

AU - Gomes, E.

AU - Pellegrini, A.

AU - Schiboni, M. L.

PY - 2006/6/7

Y1 - 2006/6/7

N2 - Background: Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results. Methods: In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16 658) were screened using conventional cytology, and women in the experimental arm (n = 16 706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (≥1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated. Results: The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at ≥1 pg/mL and at ≥2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82). Conclusions: HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.

AB - Background: Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results. Methods: In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16 658) were screened using conventional cytology, and women in the experimental arm (n = 16 706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (≥1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated. Results: The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at ≥1 pg/mL and at ≥2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82). Conclusions: HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.

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