Low CD4 count important risk factor for oral HPV infection in patients with HIV

A low CD4 count is the single most important risk factor for oral human papillomavirus (HPV) infection in HIV-positive patients, investigators from the United States report in the online edition of the Journal of Infectious Diseases.

The risk of oral HPV was increased four-fold for individuals with a CD4 count below 200 cells/mm3 compared to patients with CD4 counts above 500 cells/mm3. Risk factors in HIV-negative patients included a high number of sexual partners and smoking tobacco and marijuana.

“Our findings suggest there may be distinct risk factors involved with oral HPV in HIV-positive as compared to HIV-negative patients,” comment the investigators.

Glossary

cross-sectional study

A ‘snapshot’ study in which information is collected on people at one point in time. See also ‘longitudinal’.

lesion

Any abnormal change in body tissue caused by disease or injury. Often refers to Kaposi's sarcoma, which can cause skin lesions.

Rates of HPV-associated cancers of the mouth and throat are increasing in both HIV-positive and HIV-negative patients. However, it is unclear if risk factors for oral HPV infection and pre-cancerous lesions differ according to HIV infection status.

Investigators therefore designed a prospective, cross-sectional study involving disadvantaged patients seeking routine dental care in the Bronx, New York and Newark, New Jersey. Recruitment took place between 2008 and 2013, and the total study population comprised 161 HIV-infected and 128 HIV-negative individuals.

All patients were screened for oral HPV infection. A visual examination was also conducted to identify oral lesions, and those looking suspicious were biopsied. All participants were interviewed about their sexual behaviour and histories, use of tobacco, alcohol, marijuana and other drugs, and the medical records of the HIV-positive patients were checked to determine CD4 count.

Half the patients were African American and the mean age was 51 years.

Oral HPV infection was detected in 32% of HIV-positive patients and 16% of HIV-negative individuals. High-risk HPV types associated with the development of cancerous cell changes were also more prevalent in patients with HIV (8% vs 2%, p = 0.0049). Infection with multiple HPV types was detected in 13% of patients with HIV compared to 7% of HIV-uninfected patients.

The risk factors for oral HPV differed according to HIV infection status. For HIV-negative participants, significant associations were found with higher numbers of sexual partners (21 or more vs. five or fewer = OR, 9.1; 95% CI< 1.7-49.3), heavy tobacco use (20 or more pack-years vs. none; OR 9.2; 95% CI, 4.5-15.5) and smoking marijuana (OR = 4.0; 95% 1.13-12.4).

But for patients with HIV, a low CD4 cell count had the strongest association with oral HPV (below 200 cells/mm3 vs. 500 cells/mm3 = OR 4.5%; 95% CI, 1.3-15.5).

HIV-positive men-who-have sex with men (MSM) and women-who-have-sex-with women (WSW) were more likely to have oral HPV than heterosexual HIV-infected patients. But any association with increased risk of oral HPV ceased to be statistically significant after taking into account CD4 count.

Of the patients with oral lesions, 15% had potentially pre-cancerous lesions. In HIV-negative patients, high-risk HPV types were detected more often in patients with potentially cancerous lesions compared to non-lesion patients (OR = 21.3; 95% CI, 1.12-367). However in patients with HIV, no association was found between concurrent detection of potentially cancerous lesions and high-risk (OR = 0.8; 95% CI, 0.1-3.9) or low-risk (OR = 0.9; 95% CI, 0.2-3.6) HPV types.

Regardless of HPV infection status, the most frequent HPV type detected in patients with benign and pre-cancerous lesions was HPV32/42.

The investigators note “HPV32 has been shown…to evade the immune system by actively suppressing inflammatory responses in adjacent underlying tissues.”

Several limitations are acknowledged by the authors. These include the small sample size, the cross-sectional design and the use of visual examination to diagnose lesions. They therefore caution, “the role of oral HPV in progression to oral cancer in HIV-positive and negative populations remains unclear.”

Nevertheless, they conclude, “immune status appears to have a strong effect on oral HPV infection in HIV-positive individuals, which might mitigate the association with sexual risk factors. However, the high burden of oral HPV in both HIV-positive and negative individuals suggest that the mouth may be a reservoir of subclinical HPV infection with potential contribution to future oral disease.”

References

Muller K et al. Oral human papillomavirus oral lesions in HIV-positive and HIV-negative dental patients. J Infect Dis, published online 13 February, 2015.