Two rounds of screening were performed in more than 90,000 women age 25-60. In phase one, women were randomly assigned to a control group with conventional cytology (Pap) only or to an intervention group where women had HPV DNA testing plus liquid-based cytology. In phase two, which was conducted two years later, with three to five years of follow-up, the control group received conventional cytology and the women in the intervention group received HPV testing alone.
In the first round of screening a comparable number of cancers were detected in each group (nine in the cytology group vs. seven in the HPV group). However, following the second phase, a significant decrease in cases of invasive cancer was detected in the HPV group (zero cases) compared with the cytology group (nine cases).
After two screening rounds there was a significantly lower number of cases in the HPV group (7) versus the cytology group (18), indicating that HPV-based screening is more effective than cytology in preventing invasive cervical cancer. Also of note, a high proportion of cancers detected in the cytology group at the second round of screening were adenocarcinomas, which echo results reported in earlier studies that cytology is less effective in preventing adenocarcinoma than squamous-cell carcinoma.
The two-phase, randomized trial showed “a significantly lower number of cases in the HPV group versus the cytology group over the two screening rounds, indicating that the HPV-based screening is more effective than cytology in preventing cervical cancer,” wrote the study authors, who attributed the higher efficacy of HPV DNA testing to its earlier detection of clinically relevant lesions, which allowed for earlier treatment of precancers and prevention of invasive cancer. “For women aged 35 years or more, our results support the use of HPV DNA testing for primary screening at prolonged intervals, with cytology reserved for triage of HPV-positive women.”
“Our study is the first, to our knowledge, to show a greater efficacy for HPV testing versus cytology for preventing invasive cancers in a developed country, where cytological screening has been in place for years and advanced cervical cancers are extremely rare among screened women,” the authors wrote. The study was conducted within organized screening programs with more than 70% of eligible women enrolled, which suggests that the “results are applicable to routine practice,” the authors claim.
The new research complements an April 2009 New England Journal of Medicine that suggested HPV testing in rural India reduced the numbers of advanced cervical cancers and deaths, compared with other screening methods. Numerous studies of HPV testing have
focused on clinical efficacy data and the high sensitivity of HPV testing to detection cervical lesions and cancers, while the NEJM and Lancet Oncology studies importantly show an actual reduction in the incidence of invasive cervical cancer.
An additional finding revealed that “detection of CIN2 was higher in the HPV than cytology group at round one, but only slightly lower at round two, suggesting that some regressive CIN2 lesions were identified and treated in young women.” CIN2 refers to potentially premalignant lesions, which in some cases are cleared by the body’s immune system before they become cancerous.
“HPV testing shows a great deal of promise to revolutionize cervical cancer screening,” wrote Dr. Philip Castle and Dr. Hormuzd Katki of the National Cancer Institute, who provide patient management recommendations in an accompanying editorial. “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.”
Worldwide, cervical cancer affects approximately 500,000 women annually and is the second-most-common malignancy found in women. HPV testing identifies women with high-risk HPV infections that can cause cervical cancer, enabling diagnosis and treatment to be put in place before cervical cancer develops.
Citation: Guglielmo Ronco et al., 'Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial', The Lancet Oncology, January 2010; doi:10.1016/S1470-2045(09)70360-2