Studies Show High Rates of Cancer-causing Human Papillomavirus Infection among HIV Positive Women in Africa

By Liz Highleyman

Three recent studies have shown that infection with high-risk strains of human papillomavirus (HPV) is common among HIV positive African women. Left undetected and untreated, HPV infection can progress to cervical neoplasia (abnormal cell growth), and ultimately to invasive cervical cancer, which is classified as an AIDS-defining condition.
Study 1

In the first study, published in the June 11, 2008 advance online edition of Sexually Transmitted Infections, researchers looked at HPV infection in Rakai, Uganda.

The study aimed to determine whether self-administered vaginal swabs were an accurate method for detecting carcinogenic (cancer-causing) HPV strains, which would be useful in resource-limited settings where many women do not have access to regular Pap smears.

A total of 1003 sexually experienced women enrolled in a community cohort provided self-administered vaginal swab samples collected during annual home-based surveys.

Results

• The overall prevalence of carcinogenic HPV strains was 19.2%.

• The rate was 46.6% among HIV positive women, compared with 14.8% among HIV negative women (P < 0.001).

• Type-specific prevalence ranged from 0.2% for HPV type 31 to 2.0% for types 16 and 52.

• Age-specific HPV prevalence decreased significantly among HIV negative women (P < 0.001), but the decrease among HIV-positive women was not as pronounced (P = 0.1).

• Factors independently associated with a high risk of carcinogenic HPV infection were:

• younger age (AOR 4.97 for age 15-19 compared with 40+ years);

• being HIV positive (adjusted odds ratio [AOR] 4.82);

• self-reported herpes zoster, candidiasis, or tuberculosis (AOR 4.52);

• having more than 2 sex partners in the past year (AOR 2.21).

• Married women had a lower risk of carcinogenic HPV infection compared with unmarried women (AOR 0.46).

The investigators concluded that HPV prevalence and risk factors measured using self-administered vaginal swabs were similar to those seen in studies that used cervical samples. Thus, they wrote, "self-collection can be used as a substitute for cervical specimens, and provide an important tool for research in populations unwilling to undergo pelvic exam."

Study 2

The second study, reported in the June 2008 Journal of Medical Virology, looked at women in Cape Town, South Africa. This study assessed both cervical and oral HPV infection in HIV positive and HIV negative women to determine any association between infections at both sites and the difference in prevalence of HPV types.

The analysis included 115 women referred to a colposcopy clinic after diagnosis of abnormal cervical cells; colposcopy, a method of examining the cervix using a lighted microscope, is recommended as follow-up after an abnormal Pap smear. The women were classified as having high-grade cervical intraepithelial neoplasia (CIN2/3), low-grade disease (CIN1), or no CIN based on colposcopy and histology.

Results

• The prevalence of cervical HPV was 86.5% in HIV negative women and 97.1% in HIV positive women.

• With the exception of HPV type 45, which was more prominent in HIV positive women, the hierarchy of other predominant HPV types was similar in HIV positive and HIV negative women.

• HPV type 16 was most prevalent in both HIV positive and HIV negative women with CIN2/3 (41.7% vs 38.5%).

• Significantly more HIV positive women than HIV negative women were infected with multiple cervical HPV types (36.1% vs 88.2%; P < 0.001).

• HIV positive women also had more oral HPV infections than HIV negative women (45.5% vs 25.0%; P = 0.04).

• The most prevalent oral HPV types were 33, 11, and 72.

• The majority of women did not have concordant oral and cervical HPV types, possibly reflecting independent infection at the 2 sites.

• HIV-related immune suppression did not significantly impact the predominant types of cervical HPV infection, except for type 45.

The authors concluded that HIV positive women had more multiple HPV infections, and those with severe cervical disease had a similar prevalence of HIV type 16 but a lower prevalence of HPV type 18 than HIV negative women.

Study 3

Finally, as reported in the May 2008 Journal of Medical Virology, another team investigated HPV infection and cervical abnormalities and their association with HIV in 488 women who attended a health center in Nairobi, Kenya. About one third of the women (n = 155) were HIV positive, of whom 77% were untreated and 23% had taken antiretroviral drugs within the past 6 months.

Results

• Cervical HPV infection was detected in 17% of HIV negative and 49% of HIV positive women.

• Low-grade squamous intraepithelial lesions (roughly equivalent to CIN1) were observed in 6.9% of HIV negative and 21% of HIV positive women.

• High-grade squamous intraepithelial lesions (roughly equivalent to CIN2/3) or cervical cancer were seen in 0.6% of HIV negative and 5.8% of HIV positive women.

• In a multivariate analysis, HIV and HPV infection were associated with each other.

• Cervical lesions were significantly associated with high-risk HPV types and with HIV infection, depending on HPV infection.

• The prevalence of HPV infection increased with lower CD4 cell counts and higher HIV RNA levels.

• High-grade cervical lesions were strongly associated with high-risk HPV infection and low CD4 cell count.

"Immunosuppression as a result of HIV infection appears to be important for malignant progression in the cervix," the study authors concluded. "High-risk HPV infection and low CD4+ T-cell counts are the risk factors for cervical cancer."

"Nationwide prevention of HIV infection and cervical cancer screening are necessary for the health of women in this area," the investigators added.

The importance of this recommendation is underlined by past studies showing that while invasive cervical cancer is common among HIV positive women in Africa and other resource-limited settings, this does not appear to be the case in developed countries where women receive regular Pap smears, since timely screening can detect cervical neoplasia at an early, treatable stage before it progresses to cancer.

7/15/08

References

M Safaeian, M Kiduggavu, PE Gravitt, and others. Prevalence and risk factors for carcinogenic human papillomavirus infections in rural Rakai, Uganda. Sexually Transmitted Infections. June 11, 2008 [Epub ahead of print].

DJ Marais, JA Passmore, L Denny, and others. Cervical and oral human papillomavirus types in HIV-1 positive and negative women with cervical disease in South Africa. Journal of Medical Virology 80(6): 953-959. June 2008.

R Yamada, T Sasagawa, LW Kirumbi, and colleagues. Human papillomavirus infection and cervical abnormalities in Nairobi, Kenya, an area with a high prevalence of human immunodeficiency virus infection. Journal of Medical Virology 80(5):847-55. May 2008.