High rates of cervical disease and low rates of screening among women with HIV in Denmark

Women with HIV have a higher incidence of cervical dysplasia – pre-cancerous cell changes – compared to women of a similar age in the general population, investigators from Denmark report in HIV Medicine.

The incidence of pre-cancerous cell changes – cervical intra-epithelial neoplasia (CIN) stages 1-3 – was elevated among women with HIV, but rates of cervical cancer did not differ according to HIV infection status. When the analysis was restricted to women with normal cervical cytology at baseline and who were adherent to cervical screening guidelines, the incidence of CIN did not differ between HIV-positive and HIV-negative women.

“We found that WLWH [women living with HIV] overall developed more CIN in all stages compared with controls,” comment the authors. “Development of dysplasia in WLWH was predicted by younger age and most recent CD4 count < 200 cells/mm3.”

Glossary

cervix

The cervix is the neck of the womb, a tight ‘collar’ of tissue that 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.

dysplasia

Cells that look abnormal under a microscope but are not cancer.

cervical intraepithelial neoplasia (CIN)

Changes to cervical tissue which can be seen on visual examination through a colposcope. These are graded CIN1 to 3 according to severity. CIN1 is often left untreated; higher-grade lesions will probably need removing.

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.

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.

Women with HIV have a higher risk of persistent infection with high-risk types of human papillomavirus, the cause of cervical cancer. In 1993, cervical cancer was categorised as an AIDS-defining condition and since 1995 guidelines have recommended that all HIV-positive women should have intensified cervical screening consisting of two check-ups in the first year following diagnosis and annual screens thereafter.

However, in Denmark, only 3% of women with HIV have the recommended two cervical cytology tests in the first year after diagnosis and annual screening rates have remained low: in 2010 only 46% of all HIV-infected women underwent annual screening. Screening is dependent on physician referral and information provided by doctors regarding the value of annual screening for women living with HIV.

Investigators were concerned by these “remarkably low” screening rates. They designed a study to compare the incidence of cervical dysplasia and cervical cancer between HIV-positive and HIV-negative women in Denmark between 1999 and 2010.

All 1140 women who received HIV care in Denmark during the study period were included in the study. Each patient was matched with 15 controls of the same age, giving a total control population of 17,046 women. None of the participants had a history of cervical cancer or had undergone a hysterectomy.

The women with HIV contributed a total of 9491 person-years of follow-up, the HIV-negative controls 156,865 person-years.

Cumulative incidence of cervical dysplasia (pre-cancerous changes in the cervix) of any kind was two- to three-fold higher among women with HIV compared to controls. The difference was significant for CIN1+ to CIN3+ (all, p < 0.001). Four (0.4%) women with HIV developed cervical cancer as did 28 (0.2%) controls. The incidence of cervical cancer did not differ between the patients and controls. None of the HIV-positive women with cervical cancer had obtained prior cervical cytology results, but follow-up was very short for three of these individuals.

For women with HIV, a low CD4 cell count (below 200 cells/mm3) was associated with incident cervical dysplasia.

“In addition to host immunity, screening behaviour offers another explanation for the connection between low CD4 counts and cervical dysplasia,” suggest the authors. “Poor adherence to HAART, resulting in low CD4 counts, and consequent regular visits to HIV centres might act as proxies for suboptimal self-care and low adherence to recommended screening programmes.”

Younger age was also associated with increased risk of pre-cancerous cervical cell changes.

A total of 74% of women with HIV and 65% of controls had normal cervical cytology at baseline. Women with HIV had higher incidence of CIN1+ (adjusted HR, 2.48; 95% CI, 1.90-3.24) and CIN2+ (adjusted HR, 2.40; 95% CI, 1.79-3.22) but not CIN3+.

The analysis was further restricted to the 13% of HIV-positive women and 28% of controls with normal cervical cytology at baseline and who were adherent to national cervical screening programme guidelines. Within 39 months of enrolment, 67% of those with HIV and 83% of controls had undergone screening (p = 0.0006). The incidence of CIN1+ to CIN3+ was elevated among women with HIV, but not significantly so.

“The comparable risks of cervical disease seen in our subgroup of adherent WLWH and controls with normal cytology...raise the question of whether intensified screening programmes are necessary for all WLWH,” write the authors.

They conclude that women with HIV had a higher incidence of cervical dysplasia overall. Higher rates of cervical disease in women with low CD4 counts and non-adherence to screening guidelines show the need to improve screening attendance rates among high-risk patients. However, the investigators believe the comparable risk of cervical disease between HIV-positive patients and controls with normal cytology, calls for "individualised screening recommendations, including prior cervical cytology and HPV results.”

References

Thorsteinsson K et al. Incidence of cervical dysplasia and cervical cancer in women living with HIV in Denmark: comparison with the general population. HIV Medicine. DOI: 10.1111/hiv.12271 (2015).