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HIV may prompt progression of HPV infection to cervical precancer

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June 1, 2017

HPV infection appeared more likely to progress to cervical precancer in women with HIV, according to an analysis from multiple cohorts in Senegal, West Africa.

“In areas where cervical cancer screening is not widely available and HIV prevalence is high, these findings highlight that targeted screening of the high-risk HIV–positive population may provide an important step in cervical cancer prevention,” Hilary K. Whitham, PhD, MPH, research associate at University of Minnesota in Minneapolis, said in a press release. “These results also highlight that HPV vaccination of young women prior to HIV infection is an important preventive measure.”

HIV is known to interact with HPV, and HIV–positive women are at increased risk for HPV detection, precancerous lesions and cervical cancer. Studies have shown women with HIV have 1.5 to 8 times increased risk for cervical cancer.

When women have HIV, “HPV goes unchecked, replicating quickly and developing abnormal lesions which can progress to cancer,” Whitham said.

However, research has not longitudinally evaluated the natural history of HPV and cervical disease in HIV–positive women.

Whitham and colleagues evaluated the probability of transitioning between three natural history stages — normal, HPV infection and high-grade precancerous lesions — in HIV–positive and –negative women from multiple cohorts in Senegal.

Researchers followed 1,320 women (median age, 35 years) — 47% of whom were positive for HIV-1 and/or HIV-2 — for an average of 2 years between 1994 and 2010. Women underwent cytology and HPV DNA testing over 4-month intervals for a total of more than 7,900 clinic visits.

At baseline, researchers classified 36% of women as normal, 59% as having HPV and 5% as having high-grade precancerous lesions. Researchers also considered whether women had an incident natural history stage — meaning the stage differed from the preceding visit — or a prevalent stage.

Of the 1,079 cases classified as normal, 56.3% were incident. HIV–positive women had a 1.58 times (95% CI, 1.32-1.89) higher rate of HPV detection than HIV–negative women.

Of the 1,265 cases of HPV detection, 39.4% were incident. HIV–positive women had a 0.46 times (95% CI, 0.39-0.54) lower rate of regression from HPV to normal and a 2.55 times (95% CI, 1.69-3.86) higher rate of progression to high-risk precancerous lesions than HIV–negative women.

Researchers classified most cases (60.9%) of high-risk precancerous lesions as incident. HIV–positive women had a 0.57 times (95% CI, 0.26-1.29) lower rate of regression from high-risk precancerous lesions to normal.

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Researchers then sought to identify potential modifiers among HIV–positive women. They found CD4+ counts less than 200 mm3 increased risk for transition from normal to high-risk precancerous lesions (HR = 2.86; 95% CI, 0.95-8.58) in HIV–positive women. Low CD4+ count increased rate of progression from HPV to high-grade precancerous lesions (HR = 1.83; 95% CI, 1.07-3.14) and decreased rate of regression from HPV to normal (HR = 0.57; 95% CI, 0.39-0.83).

Also, HPV-16/18 appeared linked to higher rate of progression from normal to high-grade precancerous lesions (HR = 4.62; 95% CI, 1.1-19.42) and from HPV to high-grade precancerous lesions (HR = 2.2; 95% CI, 1.34-3.62), as well as a lower rate of regression to normal (HR = 0.35; 95% CI, 0.23-0.54) than other HPV types in HIV–positive women.

These results likely would be similar in women from other countries, especially other sub-Saharan African nations with high HIV rates, Whitham said. Still, she called for additional studies to confirm these results and evaluate potential differences in smoking, birth control use, and age at first sexual activity. – by Alexandra Todak

Disclosure: The researchers report no relevant financial disclosures.

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PERSPECTIVE
Steven C. Rubin

Stephen C. Rubin

This is an important study that adds another piece to the puzzle regarding the interactions between HIV and infection with HPV — the cause of cervical cancer. It has previously been known that women with HIV infection have a higher chance of developing HPV infection, cervical precancers, and cervical cancer itself, and that their cervical cancers may progress more quickly than those in HIV–negative women.

This large, well-conducted study showed for the first time that HIV–positive women who are infected with HPV are less likely to clear the infection, and more likely to progress to cervical precancers than HIV–negative women, presumably because their impaired immune systems are less able to eliminate the HPV infections.

The study should be a reminder to physicians that women with HIV infection should undergo regular screening for cervical cancer.


Stephen C. Rubin, MD
Fox Chase Cancer Center

Disclosure: Rubin reports no relevant financial disclosures.