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Cervical Cancer Screening that Includes HPV Test Better than Pap Smear Alone, Study Concludes

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February 19, 2014

Based on analysis of data from four large, randomized clinical trials, an international HPV screening working group has concluded that screening with a test for human papillomavirus (HPV) in addition to a Pap smear is more effective than Pap smears alone in reducing the rate of invasive cervical cancer.

HPV is one of the most common sexually transmitted diseases in the United States. While most HPV infections resolve without treatment or complications, those caused by high-risk types of HPV that persist can result in precancerous changes in cervical cells (cervical intraepithelial neoplasia, CIN) and can develop into invasive cervical cancer in women.

While HPV causes the vast majority of cervical cancers, invasive cervical carcinomas can be prevented by using screening tests to detect HPV and treating pre-cancers before they develop into cancer or become invasive. The HPV screening test detects the DNA of the virus itself in a sample of cells from the cervix – even before any cervical cell changes occur – whereas a Pap smear can only identify precancerous or abnormal cervical cells already present.

Currently, most major U.S. health organizations recommend that both tests be performed every 5 years for women ages 30 to 65 but note that a Pap test performed alone every 3 years is an option. For women between the ages of 21 and 29, they recommend a Pap smear alone every 3 years. An HPV test is not recommended because HPV infections are relatively common in this age group and often resolve without treatment or complications. However, an HPV test should be performed if the result of a Pap smear is abnormal.

To further examine the performance of these tests, the international HPV screening working group studied the data from four trials in Sweden, the Netherlands, England, and Italy that compared the two screening methods. The group reported results of its analysis online in The Lancet on November 3, 2013.

The trials involved over 176,000 women ages 20-64 who were randomly assigned to a Pap smear-based screening group (control arm) or an HPV-based screening group of either HPV testing in addition to Pap smears or HPV testing alone (experimental arm). The women were then followed for a median of 6.5 years.

Participants who tested positive, either by HPV or Pap test, depending on the study, were referred for colposcopy, a procedure used to examine the cervix for abnormal areas, which can then be biopsied and treated as necessary. The trials varied in terms of the frequency of repeat testing. Over the course of the study, 107 women with invasive cervical carcinomas were identified.

Detecting and treating pre-cancers early should decrease the occurrence of invasive cancers. In the first 2.5 years of the study, the rate of detection of invasive cervical cancer between the two screening protocols was the same. However, after that time point, detection of invasive forms occurred significantly less often in women randomly assigned to screening that included HPV testing. Thus, the working group concluded that screening with both Pap smears and HPV tests allows for earlier detection and treatment of pre-cancers and provides greater protection against the development of invasive cancer.

In addition, HPV screening was found to be most effective in women ages 30 to 34 and, for all women, HPV screening every 5 years offered better protection than Pap smears every 3 years. In particular, the cumulative incidence of invasive cervical cancer 5.5 years after a negative HPV test (with or without a negative Pap smear) was lower than the incidence 3.5 years after a negative Pap smear result without HPV testing. The researchers concluded that a 5-year HPV-based screening interval is safer than a 3-year interval for Pap smears.

Results of this study add to the growing evidence that screening that includes HPV DNA tests outperforms screening using Pap smears alone. Though this evidence may eventually lead to a change in U.S. screening recommendations, women should continue to follow currently established guidelines and talk to their health practitioner about getting screened.

One of the best forms of prevention is the HPV vaccine. It protects against infections caused by those strains of HPV that most commonly cause cervical cancer and is recommended for people 9 to 26 years old. It is most effective when given at a young age and before first exposure to the virus. Cervical cancer may also be prevented by avoiding risk factors such as smoking, having multiple sex partners, and having unprotected sex.

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Tests: HPV Test, Pap Smear
Conditions: Cervical Cancer, STDs
Screening: Cervical Cancer [Young Adults, Adults, Adults 50 and Up]

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Article Sources

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used. To access online sources, copy and paste the URL into your browser.

Ronco, G et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. The Lancet 3 November 2013. Available online at through Accessed February 2014.

Amy Orciari Herman. HPV-Based Screening Outperforms Cytology in Reducing Invasive Cervical Cancer. November 4, 2013. Journal Watch. Available online at through Accessed February 2014.

Charles Bankhead, Staff Writer, MedPage Today. HPV Testing Tops Pap for Cancer Prevention. Published Nov 6, 2013 and Updated Nov 7, 2013. Available online at through Accessed February 2014.

Roxanne Nelson. HPV Testing: Greater Protection Against Cervical Cancer. Medscape Medical News. November 02, 2013. Available online at through Accessed February 2014.

Colposcopy - directed biopsy. MedlinePlus Medical Encyclopedia. Available online at Accessed February 2014.