Improved surveillance of cervical cancer recommended in populations with high HIV prevalence

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Cervical cancer prevention guidelines may need to be reviewed to address the particular needs of HIV-infected women, due to poorer outcomes of treatment for precancerous cervical changes, data from a South African study suggest.

Priya Batra of Columbia University and colleagues from the University of Cape Town reported on a retrospective study evaluating the impact of HIV status of excisional treatment for cervical intraepithalial neoplasia (CIN), a human papillomavirus (HPV)-associated precursor lesion to cervical cancer at the Fifth International AIDS Society conference in Cape Town.

Once CIN has developed it can be detected in women through pap smears and easily treated by large loop excision of the transformation zone (LLETZ), a procedure where the HPV-induced cells in the lesion are excised by a large thin loop used to cut into the cervix encompassing the lesioned area.

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.

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.

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.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

referral

A healthcare professional’s recommendation that a person sees another medical specialist or service.

The study aimed to evaluate the impact of HIV status on LETTZ outcomes. Annual incidence of CIN is four to five times greater in HIV-positive women.

778 women referred to Groote Schuur Hospital, the primary referral centre for women in the Western Cape in South Africa, who had undergone LLETZ for the treatment of CIN were included in the study. Medical records and pathology databases of patients were reviewed from 2006 to 2008. Patients were followed up to four months post-LLETZ procedure. 46.3% (360) of the women in the study were self-reported as HIV-positive and 51.7% (186) of these women were on antiretroviral therapy (ART) at the time of their first visit.

21.9% of all women undergoing LLETZ were lost to follow up at four months and these women were significantly more likely to be HIV-positive. 55.1% of the LLETZ specimens had one or both excision margins positive for residual CIN.

The study found that HIV-positive women had suboptimal treatment outcomes, with higher proportions of abnormal pap smears and positive margins four months after excision. There was no difference in severity of disease in the HIV-positive and HIV-negative women.

30.2% of the women had incomplete treatment with persistent cervical disease at four months after excision found through abnormal pap smears. Incomplete treatment was found to be associated with residual CIN at excision margins. It was also found to be significantly associated with positive HIV status (p

45% of HIV-positive women were incompletely treated by LETTZ, as compared to only 16.8% in HIV-negative women. This difference was found to be statistically significant. Among HIV-positive women, treatment failure occurred significantly more frequently among those women who were receiving ART, compared to 37.1% who were not receiving it (p=0.0335).

Although ART may appear to not be protective in this study, the investigators could not be sure of this finding as no data were available on duration of ART or the CD4 count of patients. ART use may also be a proxy measure for low CD 4 count as ART is initiated at less than 200 cells per mm3. This may also be due to ART initiation occurring after persistent infection of HPV, since it would not prevent genetic changes which lead to cervical cancer from occurring.

The findings of suboptimal LLETZ treatment outcomes in HIV-positive women replicate those of previous studies in many developed and developing settings. Findings of an unclear cervical benefit of ART in previous studies has also been mixed with some American and European studies suggesting that ART improves regression of CIN, while others have not shown any specific benefit in this case even when taking CD 4 levels into account.

The authors suggested that primary preventative interventions such as providing HPV vaccines in populations with high HIV prevalence need further investigation. Cervical cancer prevention guidelines may need to be revised to address the special needs of HIV-infected women and to achieve better population-wide screening coverage, they say.

Further information

A powerpoint presentation by Priya Batra and a webcast of the conference session in which it was presented are available on the IAS 2009 website.