People living with HIV, especially women, may develop
lung cancer at an earlier age and with a less extensive smoking history than
people in the general population, according to a study presented at the
Conference on Retroviruses and Opportunistic Infections (CROI 2019) last week
in Seattle. These findings suggest that lung cancer screening guidelines like
those in the United States may miss many HIV-positive people who could benefit
from earlier detection and treatment.
"People
with HIV may not be adequately captured by current screening recommendations,"
Dr Subhashini Sellers of the University
of North Carolina at Chapel Hill told conference attendees.
As people with HIV live longer thanks to effective
antiretroviral treatment, non-communicable diseases such as cancer and
cardiovascular disease account for a growing proportion of deaths.
Lung cancer – the
leading cause of cancer-related death worldwide – is one of several non-AIDS
malignancies that occurs
at a higher rate in people living with HIV. In addition, people with
HIV are diagnosed with lung cancer at an earlier age on average and have worse
outcomes including shorter survival, Sellers said. HIV-positive people are more
likely to smoke than their HIV-negative counterparts, but immune system
impairment and other HIV-related factors may also contribute to this disparity.
Lung cancer often does not cause symptoms at early stages and many
people are diagnosed late, when it is more difficult to treat. The National Lung
Screening Trial, which enrolled more than
53,000 current and former heavy smokers in the United States, found that
people who received annual low-dose computerised tomography (CT) scans had a 20%
lower risk of lung cancer death.
The United
States Preventive Services Task Force (USPSTF) recommends annual CT screening for people age 55 to 80 with a cumulative smoking history of at
least 30 pack-years, who either still smoke or have quit within the past 15
years. Nonetheless, a
recent study showed that the vast majority of current and former
heavy smokers do not receive regular screening.
Current UK guidelines do not recommend lung cancer screening and it is
not routinely offered through the National Health Service.
Sellers and colleagues
evaluated whether the criteria used in the National Lung
Screening Trial – which excluded HIV-positive people – are adequate to
identify lung cancer in men and women living with HIV. They also looked
at whether alternative thresholds might improve lung cancer detection rates in
this population
The analysis included all
people with confirmed lung cancer who were age 40 or older and current or
former smokers in two large observational cohorts, the
Women’s Interagency HIV Study (WIHS) and the Multicenter AIDS Cohort Study
(MACS). They were matched with similar HIV-positive control subjects without lung cancer from the same cohort.
Sellers reported that 44
women in WIHS and 17 men in MACS were diagnosed with lung cancer during the
study period. Lung cancer incidence was 270 per 100,000 person-years among
women and 104 per 100,000 person-years among men, a significant difference. These
findings mirror trends
in the general population, with stable incidence among women and decreasing levels
among men, she said.
Women with lung cancer had a significantly lower
median CD4 cell count than control subjects without lung cancer (348 vs 452,
respectively); the difference in viral load did not reach statistical significance.
Among the men, neither the difference in CD4 count (387 vs 549, respectively) nor
viral load was significant.
Women
with and without lung cancer were about equally likely to still smoke (61% vs
59%) and to have a smoking history of 30 pack-years or more (30% vs 20%, not a
significant difference); however, those with lung cancer were nearly twice as
likely to have quit 15 or fewer years ago (93% vs 56%). Among men, those with
lung cancer were much more likely to still smoke and to have at least a 30
pack-year history (71% vs 24% for both), but in both groups nearly all who quit
had done so within the past 15 years.
The researchers found that only 16% of women and 24%
of men diagnosed with lung cancer met the USPSTF screening criteria.
For HIV-positive women, decreasing the age threshold,
amount of time since smoking cessation ('quit time') or number of pack-years –
while holding the other two variables steady – all increased sensitivity, or
ability of the criteria to accurately identify those with lung cancer. In men,
lowering the screening age from 55 to 40 made the biggest difference. Adding low
CD4 count or an AIDS diagnosis did not further improve the performance of the
criteria.
The researchers determined that the optimal criteria
for HIV-positive women would be to start screening at age 49 with a smoking
history of 16 or more pack-years and a quit time of 15 years (52% sensitivity;
75% specificity). For HIV-positive men, the optimal criteria would be age 43
with a smoking history of more than 19 pack-years and a quit time of 15 years (82%
sensitivity; 76% specificity). That is, these findings suggest that the smoking
threshold for screening should be halved for women and reduced by a third for
men living with HIV.
"Current USPSTF lung cancer screening guidelines performed
poorly in people living with HIV," the researchers concluded.
"Alternative thresholds of younger age and decreased pack year history and
quit date can better identify people living with HIV to screen for lung
cancer."