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Dr Deborah Konopnicki from Belgium gave a fantastic overview of the current research in prevention and treatment of HPV-related malignancies in HIV positive men and women on Day 3 of the Glasgow Congress.
HPV-associated infections and lesions are more frequent and their outcome is more severe in persons living with HIV. The prevalence and incidence of precancerous lesions of the cervix/vulva/vagina are 6 times higher, and of the anal region are 15 times higher than in HIV negative people. Recurrence of these lesions is also twice as frequent after treatment. Rates of cancer of the cervix are three times higher than in the general population, and rates of anal cancer are 40-100 times higher. Mortality rates from HPV-associated cancers are high, particularly in the case of anal cancer.
Antiretroviral therapy against HIV decreases HPV-associated infections and lesions after several years of optimal viral control and immuno-restoration of high magnitude.
A new preventative vaccine that targets 9 different strains of high risk HPV was approved by the FDA in 2014/5 (Gardasil9). The newer vaccine is associated with a greater reduction in rates of squamous intraepithelial lesions in women (79% reduction versus <30% reduction) and AIN in men (89% versus 62%) than the vaccines targeting genotypes 16 and 18 alone.
Due to its high cost, it has been suggested that perhaps one or two, rather than three, doses of the vaccine could be administered, but there is no evidence for the effectiveness of fewer than three doses of the vaccine in the HIV positive population. It has unequivocally been proven that HPV vaccination is beneficial for both primary and secondary prevention of HPV-related lesions in this population, although guidelines vary regarding the upper limit of age at which they should beneficially be administered as primary prevention.
Recent changes in cervical screening in the general female population in high resource settings are also application to HIV positive women: under the age of 30, HPV prevalence is too high to warrant the use of HRHPV screening; after 30, HPV testing has good negative predictive value for women with CD4>500, so future screening may potentially be conducted at lower frequency than current guidelines in this population.
A new approach to cervical screening studied in limited resource settings in South Africa, Botswana and India over the past few years has been the “screen and treat” intervention. This involves visual inspection of the cervix and high risk HPV screening – the results are available within two hours and high grade CIN can be treated on the same day with cryotherapy of trichloracetic acid. This approach has been shown to significantly decrease the incidence of HGCIN and cervical cancer at 3 years.
Another interesting development in this area has been the use of topical Lopinavir to treat CIN. A single-arm, proof-of-concept trial was conducted by Lynne Hampson et al in Kenya, in which vaginal self-application of Lopimune (Lopinavir/Ritonavir) gel was used to treat high grade CIN in 23 HIV-negative women. The intervention was well-tolerated and systemic absorption was weak; cytological response at month 3 was 82%, with 64% resolution of the CIN and 18% regression to a lower grade. The effect of the gel was thought to be due to Lopinavir’s local anti-proliferative effect on cells, and similar cervical concentrations would not be achieved with oral Lopinavir treatment.
There are limitations to anal cancer screening – although high resolution anoscopy is the gold standard it is costly and time-consuming, and so far no RCTs have shown a reduction in mortality from anal cancer with any screening program. Results from two RCTs on the use of anoscopy that are currently underway are due in 2018 and 2022. Dr Konopnicki stated that her clinic in Belgium incorporates both cervical screening and anoscopy as part of routine care for HIV positive patients, however.
Finally, therapeutic vaccines made of the E6 or E7 oncogenes (genotype-specific) or their DNA to induce cellular immune response against E6 or E7 are in development, and in the future they could contribute to less aggressive ablative therapy for HPV associated lesions.