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Women with HPV without cellular abnormalities at increased risk for cervical cancer

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December 10, 2018

Women positive for HPV16 or HPV18 but who do not have any cellular abnormalities remain at an increased risk for cervical cancer and its precursor lesions, according to results of a nested case-control study published in Cancer.

In women aged 30 years or younger, HPV16 or HPV18 was specifically associated with an increased risk for cervical intraepithelial neoplasia grade 2 or worse (CIN2+), whereas these HPV types and others increased risk among older women.

These findings can help change guidelines for cervical cancer screening, according to study researcher Sonia Andersson, MD, PhD, senior consultant at the department of women’s and children’s health at Karolinska University Hospital and Institute.

“These findings can help the ongoing development of guidelines for cervical cancer screening. They strongly indicate that testing for HPV needs to be incorporated into screening programs,” Andersson said in a press release. “Women younger than 30 with a positive HPV16 or HPV18 finding need to be closely followed, whereas other HPV types are much less likely to be associated with increased risk in these women. Among women above age 30, any HPV positive funding should be closely followed.”

The known relationship between high-risk types of HPV and cervical cancer and its precursor lesions has led to the use of sensitive HPV molecular tests for screening. Trials conducted in the U.S. show that genotyping for HPV16 and HPV18 improved risk stratification for women with cytology negative for intraepithelial lesions or malignancy; however, there are limited data to support this strategy from outside the U.S.

Andersson and colleagues analyzed 576 women over a 9-year period who had normal findings on their baseline liquid-based cytology of the cervix.

Over the 9-year period, 92 of the women developed high-grade CIN and four of the women developed cervical cancer. These were known as the case group.

The other 480 women who did not develop cervical cancer or CIN were known as the control group.

Researchers then retroactively tested baseline cervical samples for HPV and found that women with HPV were much more likely to be part of the case group than the control group. Fifty-one percent of cases compared with 14% of controls had any HPV detected (P < .001).

Among women aged 30 years or younger, the presence of HPV16 or HPV18 indicated a significantly higher risk for CIN2+ (OR = 9.44; 95% CI, 3.37-2.64) and CIN3+ (OR = 19.2; 95% CI, 4.22-87.3); however, other types of HPV did not show this association.


Among women aged 30 years or older, HPV16 and HPV18, as well as numerous other types of HPV, indicated a significant risk for CIN2+ (HPV16/18, OR = 8.16; 95% CI, 3.28-20.3; other HPV, OR = 9.04; 95% CI, 3.42-23.9) and CIN3+ (HPV16/18, OR = 17.8; 95% CI, 2.84-82.9; other HPV, OR = 7.12; 95% CI, 2.05-24.8).

Limitations of this study included that samples were stored for long periods of time — from 9 to 11 years — at room temperature, which may have caused HPV DNA degradation.

Further limitations included a lack of follow-up data on HPV, which could have reduced the associations found in the study, and a small number of cases in women aged 50 years or older.

“The finding of HPV is clearly vital in identifying women with [cytology negative for intraepithelial lesions or malignancy] who are more likely to develop high-grade CIN,” Andersson and colleagues wrote. “Nevertheless, there is a proportion of women with [cytology negative for intraepithelial lesions or malignancy] findings and negative tests for HPV who develop high-grade CIN.” – by John DeRosier

Disclosures : The Swedish Cancer Foundation, Karolinska Institute, Swedish Research Council, Stockholm County Council and the Gustaf V. Jubilee Fund funded this study. Andersson reports no relevant financial disclosures. One author reports grants from the 7th Framework Programme of DG Research and Innovation and from VALGENT during the conduct of the study.

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