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HPV Screening Better Than Cytology in Preventing Invasive Cervical Cancer

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Key Points

  • The overall rate ratio for invasive carcinoma for HPV screening vs cytology screening was 0.60 (95% CI = 0.40–0.89), including a rate ratio of 0.45 (95% = CI 0.25–0.81) at > 2.5 to 5 years after enrollment.
  • Among women with an initial negative test result, the overall study-adjusted rate ratio was 0.30 (95% CI = 0.15–0.60).
  • The rate ratio was lowest in women aged 30 to 34 years (0.36, 95% CI = 0.14–0.94).

In a study reported in The Lancet, Guglielmo Ronco, MD, of the Center for Cancer Epidemiology and Prevention, AO City of Health and Science, in Turin, Italy, and colleagues in the International HPV Screening Working Group performed a follow up of four randomized trials of human papillomavirus (HPV)-based vs cytology-based cervical screening to determine their relative efficacy in prevention of invasive cervical cancer. They found that HPV screening was associated with a marked improvement over cytology screening in cancer prevention.

Study Details

The study involved 176,464 women aged 20 to 64 years who were randomly assigned to HPV-based or cytology-based screening in trials in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). After initial screening in these trials, participants with negative results were invited for additional screening rounds at 3 years in three of the studies and at 5 years in one study. The endpoints in these trials were cancer precursors.

In the current analysis, the women were followed for a median of 6.5 years (1,214,415 person-years), during which 107 invasive cervical carcinomas were identified through linkage with screening, pathology, and cancer registries and masked review of histology specimens. Cumulative and study-adjusted rate ratios were calculated for incidence of invasive cervical carcinoma.

Rate Ratios for HPV vs Cytology Screening

Among all women, the rate ratio for invasive cervical carcinoma for the HPV group vs cytology group nonsignificantly favored HPV screening during the first 2.5 years of follow-up (0.79, 95% confidence interval [CI] = 0.46–1.36) and significantly favored the HPV group at  > 2.5 to 5 years (0.45, 95% CI = 0.25–0.81). The cumulative detection of invasive carcinoma was 46.7 per 105 in the HPV screening group vs 93.6 per 105 in the cytology screening group at 8 years after enrolment, with the rate ratio being significantlyin favor of HPV screening (0.60, 95% CI = 0.40–0.89). No differences in rate ratios among the four studies were observed (P = .52 for heterogeneity).

Among women with a negative test result on study entry, the cumulative incidence of invasive cervical cancer for the HPV vs cytology group was 4.6 vs 15.4 per 105 at 3.5 years and 8.7 vs 36.0 per 105 at 5.5 years; the overall study-adjusted rate ratio was 0.30 (95% CI = 0.15–0.60), with no differences observed among studies (P = .23 for heterogeneity).

Outcomes by Stage, Histology, Age

The proportion of adenocarcinomas decreased according to age from 40% in women aged < 30 years to 35% in those aged 30 to 34 years, 30% in those aged 35 to 49 years, and 23% in those aged ≥ 50 years. The rate ratio was lower for adenocarcinoma (0.31, 95% CI  = 0.14–0.69) than for squamous cell carcinoma (0.78, 95% CI = 0.49–1.25). Rate ratios did not differ by cancer stage.

The rate ratio was lower in women aged 30 to 34 years (0.36, 95% CI = 0.14–0.94) than in those aged < 30 years (0.98, 95% CI = 0.19–5.20), 35 to 49 years (0.64, 95% CI = 0.37–1.10), and ≥ 50 years (0.68, 95% CI = 0.30–1.52). However, there was no significant difference in rate ratio for the 30 to 34 year age group compared with women aged ≥ 35 years (P = .13).

The investigators concluded, “HPV-based screening provides 60-70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years.”

The study was supported by European Union, Belgian Foundation Against Cancer, KCE-Centre d’Expertise, IARC, The Netherlands Organisation for Health Research and Development, and the Italian Ministry of Health.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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