We’re on the way to ending cervical cancer

It could be the end of the affair with HPV!¹ With this exclamation, Prof. Margaret Stanley, the noted human papillomavirus immunologist, expressed the optimism we all share, now that the possibility of conquering cervical cancer is within view. Not yet 25 years have passed since the first sequencing of a genital HPV type, and scarcely 10 years since the International Agency for Research on Cancer proclaimed that HPV causes cervical cancer. It has been 57 years since the discovery that launched an international quest to reduce the cervical cancer rate: George Papanicolaou’s test for early abnormal cell changes that, decades later, were found to be secondary to HPV. We’ve made great progress. What was the 2nd leading cancer in US women in incidence and mortality is now 11th in incidence and 13th in mortality.

But even with perfect attendance at annual screenings, women still get cervical cancer. And many still do not have screenings—they account for about half of all cervical cancers. And the Pap, as good as it is, has flaws. The test is subjective, and sensitivity varies from lab to lab and country to country.

What is new in 2006 that we may soon be able to put into practice, bringing us closer to a new world—with respect to cervical cancer prevention—different from any we’ve known?

• 1 More sensitive and objective screening
• 2 Better management of screen positives
• 3 HPV vaccine, soon to be in our offices

1 More sensitive and more objective screening

A comforting combo: Negative Pap and HPV tests

ACOG Practice Bulletin, Number 61. Human papillomavirus. Washington, DC: American College of Obstetricians and Gynecologists; April 2005.

Because HPV testing is more sensitive than cervical cytology in detecting CIN 2 and CIN 3, women with concurrent negative Pap and HPV tests can be reassured that their risk of unidentified CIN 2, CIN 3, or cervical cancer is approximately 1 in 1,000. (Level A evidence)

The American Cancer Society and the American College of Obstetricians and Gynecologists have both provided as an option the screening of women age 30 and older with the combination of the Pap and a test for high-risk HPV types.^2,3 These “sophisticated new tests for the detection of HPV…hold great promise for improved screening for cervical cancer precursors and invasive cancer, and for triage of cervical cytology,” the Bulletin states.

Not all women get annual screening, however, and even if they do, the IARC estimates, the lifetime risk for cervical cancer for women who have conventional Paps annually is approximately 216 per 100,000, if the Pap sensitivity is about 70%. The prospect of reducing the risk of missing significant cervical neoplasia at each screen to 1 per 1,000 should be of comfort to women and the clinicians who watch over their health.

Dilemma: Women over 30, with normal Pap and high-risk HPV

What about the approximately 4% of women aged 30 and older with normal cytology and high-risk HPV? How should these women be managed? A panel of experts on HPV and cervical screening published “interim guidance” in 2004, recommending that until further data are available, these women should be retested in 6 to 12 months for persistence of HPV or development of abnormal cytology, and referred to colposcopy if still HPV-positive or if Pap results show low-grade squamous intraepithelial lesion (LSIL) or worse, regardless of HPV result.⁴

Although the April 2005 ACOG Bulletin affirmed that guideline, concern persisted that, while some women so identified might be better evaluated immediately by colposcopy, the majority would not, and there was no good way to identify HPV-positive women most at risk. Several longitudinal studies (discussed in the following section) have now made the path clearer.

REFERENCES

1. Stanley M. The end for genital human papillomavirus infections? Lancet Oncol 2005;6:256-257.

2. Sasow D, Runowicz CD, Solomon D, et al, for the American Cancer Society. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin. 2002;52:342-362.

3. ACOG Practice Bulletin, Number 45. Cervical cytology screening. Washington, DC: American College of Obstetricians and Gynecologists; 2003.

4. Wright TC, Jr, Schiffman M, Solomon D, et al. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gynecol. 2004;103:304-309.

Type-specific testing identifies highest risk