Invasive cervical cancer risk no higher in women with HIV

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Women with HIV have a low incidence of invasive cervical cancer (ICC) despite a high prevalence of risk factors, according to an American study published in the January 2nd 2004 edition of AIDS.

Researchers analysed data from the Women’s Interagency HIV Study (WIHS), a multicentre prospective cohort study of the natural history of HIV in seropositive women and women at risk for HIV infection. Data were collected from October 1994 through September 2001.

Women who had cervical cancer before enrollment, had undergone a hysterectomy, or for whom follow-up data were incomplete were excluded from the analysis, leaving 2131 women (1661 HIV-positive, 462 HIV-negative, and eight who seroconverted during the observation period). Median age at enrollment was 36 for the HIV-positive women and 34 for the HIV-negative women; slightly more than half were African-American, about one-quarter were Latina, and about 17% were white.

Glossary

cervix

The cervix is the neck of the womb, at the top of the vagina. This tight ‘collar’ of tissue closes off the womb except during childbirth. Cancerous changes are most likely in the transformation zone where the vaginal epithelium (lining) and the lining of the womb meet.

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.

squamous intraepithelial lesion (SIL)

This term is used to describe the detection of abnormal cells that have been ‘transformed’ by HPV into a possibly pre-cancerous state. According to the degree of cell change this will be called low-grade or high-grade SIL (LSIL or HSIL). If SIL is detected, a colposcopy will usually be ordered.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

invasive

In medical terms, going inside the body.

Cervical cytology tests (Pap smears) were performed every six months. Results were graded according to the Bethesda System, which classifies cervical cells as normal, atypical (atypical squamous or glandular cells of undetermined significance; ASCUS or AGCUS), low-grade or high-grade squamous intraepithelial lesions (SIL), or carcinoma. Women who had evidence of atypical cervical cells (ASCUS/AGCUS or higher) were referred for colposcopies and individualised follow-up care. All potential diagnoses of ICC were confirmed by a gynaecologic pathologist. PCR testing for human papillomavirus (HPV) was also performed.

At study entry, 62.7% of the HIV-positive women and 31.7% of the HIV-negative women had evidence of HPV infection; 13.6% and 3.6%, respectively, had oncogenic HPV strains associated with cervical cancer. At baseline, 37.7% of the HIV positive women and 17.3% of the HIV negative women had abnormal cervical cytology of any grade, mostly ASCUS (19.5% and 10.8%), AGCUS (1.9% and 2.7%), or low-grade SIL (14.1% and 2.5%). High-grade SIL was seen in 32 (2.1%) of the HIV-positive and 6 (1.4%) of the HIV-negative women, while only one HIV-positive woman and no HIV-negative women had cervical carcinoma.

After 2375 person-years of observation, no new ICC cases were detected in the HIV-negative women. After 8260 person-years, eight potential new cases were identified in the HIV-positive women, but only one was confirmed as ICC. The incidence rate of ICC among the HIV-positive women was thus 1.2 per 10,000 person-years (95% confidence interval, 0.3–6.7 cases). There was no significant difference in ICC incidence between the HIV-infected and uninfected women (p=1.0).

“Among U.S. women with HIV enrolled in a regular cervical cancer prevention program, the incidence of ICC is only 1.2/10,000 woman-years, a low risk statistically indistinguishable from that in HIV seronegative women and similar to that reported among age- and race-matched women in the general population,” the authors concluded.

ICC is a diagnostic criterion for AIDS in the U.S. and Europe. Previous research has shown that the incidence of cervical cell abnormalities is high and recurrence is common in HIV-infected women. Women with HIV also have been observed to have high rates of infection with oncogenic HPV strains. However, early research on cervical disease in women with HIV was done before the advent of HAART and participants often had advanced immune suppression.

“[W]e have found that HIV-infected women, despite having an amalgam of risks for cervical cancer and despite previous assertions of substantive increases in ICC prevalence, have reassuringly low ICC incidence rates when in programs that provide careful monitoring for cervical disease,” the researchers said.

Women in the WIHS cohort received regular cervical screening and follow-up care, which may have prevented atypical cervical cells from progressing to carcinoma. In addition, effective combination antiretroviral therapy was rapidly adopted among this group after protease inhibitors became available in 1996; about half were receiving HAART by 1998.

The authors cautioned that the low ICC incidence rate seen in this study may not be generalized to women who do not receive regular screening and prevention, nor to those who are not taking antiretroviral therapy. They emphasized that clinicians should follow standard recommendations for cervical cancer surveillance and management, including two cytologic screenings in the first year after HIV diagnosis and annually thereafter, a colposcopy if atypical cells are detected, and appropriate follow-up treatment.

Reference

Massad LS et al. Low incidence of invasive cervical cancer among HIV-infected U.S. women in a prevention program. AIDS 18: 109-113. 2004