HPV Tests More Sensitive Than Pap Tests for Cervical Cancer Detection

A. Kott

First published online:

Human papillomavirus (HPV) tests that use self-collected vaginal samples are more sensitive than clinically performed Pap smears for detecting precancerous cervical lesions and invasive cervical cancer, a population-based randomized trial conducted in Mexico indicates.1 The HPV tests were three times as effective as Pap smears in detecting cervical abnormalities of at least moderate severity, and four times as effective in detecting cervical cancer. However, HPV tests also yielded more false-positive results than did Pap smears.

Cervical cancer takes an especially great toll in developing countries, which typically lack the resources to sustain clinical screening and prevention services. HPV testing may be particularly useful in these settings, because it is less expensive and more convenient than performing and evaluating Pap smears. In addition, under optimal conditions, HPV testing is more effective than Pap smears in detecting precancerous and cancerous lesions. To examine whether this is true in a low-resource country, researchers conducted a randomized equivalence trial comparing HPV tests of self-collected vaginal samples against routine analyses of Pap smears.

From March 2006 to April 2007, investigators recruited women aged 25–65 from 540 medically underserved, largely rural communities in three Mexican states. Participants had to be enrolled in Oportunidades, a poverty-reduction program for people with limited health care access and low levels of education and nutrition; in addition, they could not be pregnant or have had a hysterectomy. Women were assigned to one of two interventions: to self-collect vaginal samples at home for HPV testing, or to have a Pap smear at a local clinic. Those in the HPV-testing group were visited at home by a nurse, who taught them how to collect a vaginal sample; the samples were then tested at a laboratory. Women who tested positive for HPV or whose Pap smear indicated abnormalities were referred for colposcopy to examine the cervix, vagina and vulva in more detail; the trial’s primary endpoint was detection of cervical intraepithelial neoplasia (precancerous cellular abnormalities) of at least moderate severity, known as CIN 2.

Because some of the women who had been assigned to the self-collection group were reassigned to the Pap smear group (generally because they were not home when the nurse visited), analyses focused on the women who followed their assigned protocol—9,202 women who self-collected a vaginal sample for HPV testing, and 11,054 who underwent a Pap smear. The mean age for women in both groups was 38.

Overall, 10% of participants who had self-collected a vaginal sample tested positive for one of the HPV types that are associated with cervical cancer, while 0.4% of women who had had a Pap smear had evidence of abnormal cervical cells. Colposcopy of women with positive tests revealed that HPV testing was more effective than Pap smears in detecting precancerous or cancerous lesions: The prevalence of lesions categorized as CIN 2 or worse was 117 per 10,000 among women who had undergone HPV testing, compared with 34 per 10,000 among those who had had a Pap smear. HPV tests also detected a higher rate of invasive cervical cancer than did Pap smears (30 vs. seven per 10,000). Sensitivity analyses indicated that HPV testing was 3.4 times as sensitive as Pap smears in detecting lesions of CIN 2 or worse, and 4.2 times as sensitive in detecting cervical cancer. None of the invasive cancers in either group had spread beyond the cervix.

However, HPV testing also produced more false-positive results than did Pap smears. As a result, a positive HPV test result had a lower positive predictive value than did a positive Pap smear: Only 12% of women with positive HPV tests had CIN 2 or worse lesions, compared with 91% of those with positive Pap smears. Rates of false-positive results did not differ by age in either group.

The authors noted that the large number of false-positive HPV results—and the associated colposcopy referrals, risks of overtreatment and costs—were a major limitation of the study. Because most of these HPV-positive women will not develop precancerous or cancerous lesions, "the low positive predictive value is a burden to public health care services," they wrote. Another limitation was the absence of testing to confirm negative test results for women from both intervention groups.

Nevertheless, the authors conclude that the ability of HPV testing to detect precancerous cervical lesions and invasive cervical cancer is especially valuable for women whose limited health care access may permit only a few cancer screenings in their lifetime. "Vaginal self-sampling for HPV testing reduces the need for cytology clinics and permits an increase in screening coverage, especially in marginalized areas," they note. The challenge, they add, will be determining the most effective treatment for HPV-positive women without incurring unnecessary colposcopy costs.

–A. Kott


1. Lazcano-Ponce E, Self-collection of vaginal specimens for human papillomavirus testing in cervical cancer prevention (MARCH): a community-based randomised controlled trial, Lancet, 2011, 378(9806): 1868–1873.