Cervical cancer screening for HIV-infected women is a “must”, investigators stress in the August 15th edition of Clinical Infectious Diseases. Early detection of potentially cancerous cervical cell changes provides the best opportunity for effective treatment, and screening would benefit all women, including those in low- and middle-income countries who are gaining access to antiretroviral therapy, write the authors, from Lyon and Oxford.
There are over 17 million HIV-infected women worldwide, with 13.2 million living in sub-Saharan Africa. Low- and middle-income countries, which are hardest-hit by HIV, historically have a very high prevalence of human papilloma virus (HPV), certain strains of which are associated with anal and cervical cancer. In Uganda, by the age of 64, a woman had a cumulative risk of cervical cancer of 3.26% which compares to a cumulative risk of only 0.62% for women in England.
Because both HIV and HPV are sexually transmitted, the two infections are often found together. Furthermore, the immune suppression caused by HIV means that HPV is more likely to persist in HIV-infected women and lead to pre-cancerous and cancerous cell changes.
Screening and early treatment are important in the prevention of cervical cancer in both HIV-positive and HIV-uninfected women. In the US, 81% of HIV-infected women have annual Pap smear tests, and 94% of cases of potentially cancerous cell changes are detected early.
Some other industrialised countries do not have such a good record. In Spain, for example, 7% of HIV-positive women develop cervical cancer, with a further 62% of women having pre-cancerous cervical cell changes. And a study in Italy revealed that 50% of cases of cervical cancer developed in women with long-term HIV infection, suggesting that there was a lack of adequate screening that could have prevented disease progression.
The reasons for inadequate cervical screening in southern Europe, where there is universal access to anti-HIV therapy, are unclear. There are clear guidelines stating that HIV-infected women should have regular cervical screens, but the authors suggest that the separation of HIV and gynaecological services could be a possible reason.
In low- and middle-income countries there is little or no access to cervical screening, regardless of a woman’s HIV infection status. Before antiretroviral became more widely available in these settings, this probably made little difference to the prognosis of HIV-infected women. However, anti-HIV treatment is becoming more readily available around the world, reducing the incidence of key AIDS-defining infections.
But the impact of antiretroviral therapy on HPV is modest, and HIV-positive women who are infected with HPV remain at high risk of experiencing potentially cancerous cervical cell changes.
Cost, a lack of trained personnel, inadequate laboratory facilities, and the difficulty of retaining women in follow-up all mean that cervical screening programmes face difficulties in resource-limited settings. However, the authors suggest that money from PEPFAR could be used to provide the infrastructure needed for cervical screening programmes.
Even if this were to happen, the optimal method of cervical screening in low- and middle-income countries has yet to be determined. Although cytological screening has significantly lowered the incidence of cervical cancer in richer countries, experience from Latin America shows that high standards can be difficult to maintain, with samples often poorly collected, laboratories badly equipped and staffed by inadequately trained personnel.
Visual inspection after the application of acetic acid or Lugol’s iodine is an alternative screening strategy. It has the advantage of providing immediate results. But this test is dependent upon staff being highly trained and experienced, and in some low-income settings this means that the test only detects around 50% of high-grade pre-cancerous cell changes.
Blood tests for high-risk HPV strains (particularly HPV-16 and HPV-18) are highly sensitive and less dependent on the skill of healthcare or laboratory staff. Although the currently available tests are too expensive for resource-limited countries, a new, cheaper test is currently in the pipeline.
Vaccination only provides protection to women who are HPV-uninfected, and the safety and efficacy of the HPV vaccines have yet to be determined in HIV-infected women. It is also unknown if vaccination would provide protection against reinfection for women who have successfully cleared HPV infection.
“For the moment, the prevention of avoidable deaths due to cervical cancer rests only on early diagnosis”, conclude the authors, who add, “the real opportunity to prevent cervical cancer in women living with HIV infection in low-resource countries should not be missed.”