An article published Online First in The Lancet Oncology reports that human papillomavirus (HPV) DNA testing prevents more invasive cervical cancer compared to cytology screening alone. It detects persistent high-grade lesions which lead to cervical cancer at an earlier time. Consequently, HPV testing should become the main screening tool for women aged 35 years or older at longer screening intervals, with cytology reserved for triage of women who test positive for HPV.
DNA testing for HPV is widely recognized as superior in detection of precancerous lesions called high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) compared with cytology. However, HPV testing is less exact. It also results in more false-positive tests than conventional Pap smears. However, it is unclear whether shifting to HPV testing from standard cytology in cervical cancer screening programmes increases their effectiveness in preventing invasive cervical cancer. This is particularly true in developed countries where advanced cervical cancers are rare among screened women.
Guglielmo Ronco and colleagues from Italy led The New Technologies for Cervical Cancer (NTCC) screening study. It reviewed the benefits and risks of introducing HPV testing for cervical cancer screening and evaluated the most appropriate age for initiating HPV testing.
Two rounds of screening were done for two separate recruitment phases. Women, aged 25 to 60 years, were randomly assigned to conventional cytology only or to HPV testing plus cytology (first phase) and HPV testing alone (second phase). During both phases all women with an abnormal cytology result were referred to colposcopy. In the HPV group, during phase one all women who were HPV-positive and aged 35 to 60 years were referred to colposcopy, whereas women aged 25 to 34 years were referred to colposcopy only if cytology was also abnormal or if HPV testing was persistently positive. During phase two, women in the HPV group were referred for colonoscopy if the HPV test was positive.
A similar number of invasive cancers were detected in each group according to the findings in the first round of screening. There were nine in the cytology group compared with seven in the HPV group. But in the second round no cancers were detected in the HPV group compared with nine in the cytology group. This suggests that HPV-based screening is more effective than cytology at preventing invasive cervical cancer, probably because of earlier detection and treatment of CIN.
Significantly, for women aged 35 years or older, the combination of HPV testing with cytology did not increase the sensitivity of screening. This indicates that increased detection of CIN3 was primarily due to HPV testing.
On the other hand, among younger women aged 25 to 34 years, HPV testing led to over-diagnosis and treatment of regressive CIN2 lesions which is associated with increased risk of pregnancy-related morbidity.
The authors explain: “Our data support the use of stand-alone HPV testing as the primary screening test. The extremely low detection of CIN3 at round two in the HPV group (2 per 10 000) indicates that HPV-based screening at extended intervals is safe.”
They say in conclusion: “Further follow-up is needed to define how long screening intervals can be safely extended. Research is needed to define the optimum management of HPV-positive women…to minimise the costs related to increased referral to colposcopy and overdiagnosis of regressive lesions.”
In an associated comment, Philip Castle and Hormuzd Katki from the National Cancer Institute in the USA write in conclusion: “HPV testing shows a great deal of promise to revolutionise cervical cancer screening…We advocate that clinical management be based on estimating a woman’s individual risk of cervical precancer, rather than complex algorithms. Data from the current study could be used to develop risk estimates to make the promise of more effective and cost-effective cervical cancer prevention a reality.”
“Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial”
Guglielmo Ronco, Paolo Giorgi-Rossi, Francesca Carozzi, Massimo Confortini, Paolo Dalla Palma, Annarosa Del Mistro, Bruno Ghiringhello, Salvatore Girlando, Anna Gillio-Tos, Laura De Marco, Carlo Naldoni, Paola Pierotti, Raffaella Rizzolo, Patrizia Schincaglia, Manuel Zorzi, Marco Zappa, Nereo Segnan, Jack Cuzick, and the New Technologies for Cervical Cancer screening (NTCC) Working Group
DOI: 10.1016/S1470-2045(09)70360-2
Written by Stephanie Brunner (B.A.)