Monitoring may be an option for people living with HIV diagnosed with high-grade pre-cancerous anal lesions

Up to 62% of people living with HIV who have high-grade pre-cancerous cell changes may experience an improvement in their condition over two years without any treatment, according to the results of a modelling study presented to the recent Conference on Retroviruses and Opportunistic Infections (CROI) in Boston earlier this month.

Investigators from University of California, San Diego based the model on observed outcomes in over 2800 people with high-grade pre-cancerous anal cell changes who received care between 2001 and 2012. Calculated rates of progression to anal cancer were low at 1% - 2.2%. The investigators believe the results show that monitoring without immediate treatment might be an option for some people. However, they also acknowledge that uncertainty about the reliability of anal cytology tests makes it difficult to estimate precise rates of disease regression.

There is a high prevalence of anal human papillomavirus (HPV) infection among people living with HIV. Persistent infection with high-risk types of HPV can lead to pre-cancerous and cancerous anal cell changes and, although rare, rates of anal cancer are markedly higher in people living with HIV compared to other groups.

Glossary

human papilloma virus (HPV)

A group of wart-causing viruses which are also responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.

regression

Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.

lesions

Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

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.

exclusion criteria

Defines who cannot take part in a research study. Eligibility criteria may include disease type and stage, other medical conditions, previous treatment history, age, and gender. For example, many trials exclude women who are pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied.

Diagnosis with pre-cancerous anal cell changes can be worrying for patients. Even though treatment is available, its best use is uncertain and it can be unpleasant. 

Against this background, investigators wished to establish a better understanding of the natural history of high-grade pre-cancerous anal cell changes (anal intraepithelial neoplasia, HGAIN) in the absence of treatment. They also wished to examine the effect of different levels of diagnostic accuracy (the sensitivity and specificity of anal cytology) on the likelihood that a patient diagnosed with a high-grade pre-cancerous lesion would either develop anal cancer or cease to have evidence of a high-grade lesion within two years of diagnosis.

Progression and regression rates were estimated in a model based on retrospective cohort data on 2804 people with confirmed HIV infection and HGAIN who had at least two cyto-histological assessments of anal cell changes during follow-up between 2001 and 2012. Study participants who progressed to anal cancer within six months of first anal cytology were excluded from analysis, and results were also excluded after patients underwent a first treatment for anal intraepithelial neoplasia.

The investigators estimated the probability of disease regressing from HGAIN or progressing to anal cancer.

Participants in the cohort study were followed for a median of 3.9 years and had a median of three anal cytology assessments. A total of 74 people were diagnosed with anal cancer during follow-up, but data for 23 of these individuals were excluded from the model because the diagnosis was made within 180 days of their first cytology result.

Most participants (88%) were receiving antiretroviral therapy, 71% had an undetectable viral load and 30% had a history of smoking – a known risk factor for the progression of HPV-related disease.

Estimated rates of disease regression were between 16.5 and 64.2 per 100 person-years of risk. The wide variation was due to assumptions regarding the accuracy of anal cytology. Sensitivity of anal cytology to detect the presence of HGAIN was varied in the model between 47% and 89%.

The rate of progression to anal cancer was between 0.5 and 1.3 per 100 person-years.

The investigators believe that the validity of their findings is suggested by similar rates of spontaneous improvement among women with pre-cancerous HPV-related cervical lesions. Moreover, earlier research involving people living with HIV with HPV-associated high-grade squamous intraepithelial lesions found a disease regression rate of 41 per 100 person-years of follow-up.

HGAIN regression rates over two years therefore vary between 27 and 62% and rates of progression to anal cancer are low at 1% to 2.2%, conclude the investigators. Monitoring without immediate therapy may therefore be an option for people diagnosed with HGAIN.

References

Agmas W et al. Natural history of HIV-related anal dysplasia: a multi-state modeling analysis. 21st Conference on Retroviruses and Opportunistic Infections, Boston, 2014.