HPV load predicts risk of high-grade cervical disease in HIV-positive women

HIV-positive women with high-grade cervical intraepithelial neoplasia (CIN) have higher levels of human papilloma virus (HPV) in the cervix than women without cervical disease, according to a study presented in the 1^st February edition of Clinical Infectious Diseases. However, neither the type of HPV nor number of strains detected were associated with high-grade CIN.

The investigators, from Milan, conclude that HPV load may be used as a marker for the risk of progression of cervical disease and the development of cancer amongst HIV-positive women.

Infection of the cervix with certain strains of HPV, the wart virus, can lead to cellular abnormalities termed dysplasia or neoplasia. These may eventually progress from low-grade to high-grade lesions, and possibly to cervical cancer. It is thought that HIV infection increases the risk of progression of cervical disease, due to a lack of clearance and persistent HPV infection, even with effective anti-HIV therapy.

“The significantly higher HPV load detected in women with high-grade cervical dysplasia, as well as the dramatic difference in the load after surgical removal of the lesion, suggest that HPV load is a possible prognostic marker of high-grade squamous intraepithelial lesion,” conclude the investigators. “However, the distribution, number and types of HPV strains implicated in cases of cervical infection were not significantly different between the two groups.”

A number of studies have attempted to identify whether HPV load and the presence of ‘high risk’ HPV strains are associated with the progression of cervical disease, but with little agreement. This study was designed to assess these parameters in HIV-positive women with ‘high risk’ strains of HPV, comparing a group of HIV-positive women with high grade CIN to a second group with ‘high risk’ HPV but without high-grade CIN.

The investigators analysed the HPV load and types found in 108 samples taken from 38 HIV-positive women, all of whom had high-risk HPV. Sixteen of the women had high-grade CIN (CIN 2 or 3), while the remaining 22 had no or low-grade neoplasia (CIN 1) following examination of the cervix by colposcopy.

The two groups were matched based on age, CD4 cell count, HIV viral load and antiretroviral therapy. HPV load was determined using two techniques: the polymerase chain reaction (PCR) and the Hybrid Capture 2 (HC2) index.

All of the women underwent examination at intervals of six to twelve months, when the cervix was examined and samples were taken for analysis using Papanicolaou (Pap) smears, biopsy or cervical brushing. For women with high-grade lesions, samples were taken less than one month before surgical removal of the lesions, three to six months after surgery, and again during long-term follow-up at a median of twelve months after surgery. Samples from the women without high-grade CIN were taken at similar times, but they did not undergo surgery.

Analysis of cervical brush samples showed that the women with high-grade lesions had higher HPV loads that those without (p < 0.001 for both techniques). In addition, HPV loads decreased following surgical removal of the high-grade lesions (PCR: p < 0.001; HC2: p = 0.024).

In contrast, however, the number of different strains of HPV detected in the samples was similar between women with and without high-grade lesions, with a median of four HPV types found in samples removed during surgery. "Our data demonstrate that, in HIV-infected persons, there is a great prevalence of multiple and persistent high-risk HPV infections within a specific lesion," the investigators conclude.

They also noted no significant differences in the types of HPV strain found between the two groups, with types 16, 51 and 52 being most prevalent.

During follow-up, nine of the 16 women with high-grade lesions had relapsed, eight with low-grade and one with high-grade CIN. However, the investigators were unable to demonstrate a clear relationship between the persistence of HPV infection and the risk of relapse. Although nine women with high-grade lesions had persistent infection over the three samples, three of these did not experience relapse of CIN.

“In examining whether viral persistence is a key factor in the evolution of cervical lesions, we were faced with a very complex puzzle,” they state. “The prevalence of persistent infection among women who experienced relapse was not statistically different from the prevalence among those who did not.”