ICRH Monographs - Sonia Menon - Cervical cancer prevention in HIV-infected women within a high bacterial vaginosis setting in Kenya

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On Monday, 23th of April 2018 Sonia S. MENON succesfully defended her PhD thesis entitled: "Cervical cancer prevention in HIV-infected women within a high bacterial vaginosis setting in Kenya"

Supervisors: Prof. dr. Davy Vandenbroeck and Prof. dr. Steven Callens
Doctoral thesis submitted to the Faculty of Medicine and Health Sciences, Ghent University
 

Abstract:

Epidemiological studies have established human papillomavirus (HPV) infection as the central cause of invasive cervical cancer (ICC) and its precursor lesions. HIV is associated with a higher prevalence and persistence of a broader range of high-risk HPV genotypes, which in turn results in a higher risk of cervical disease. Similarly, there are epidemiological studies suggesting an association between bacterial vaginosis (BV) and HPV and BV, cervicitis and Cervical intraepithelial neoplasia (CIN).

ICC represents the fourth most common malignancy, affecting women globally and is the second most common in resource poor settings. Five recent WHO global recommendations in the cervical cancer primary and secondary prevention landscape are likely to have an impact on cervical cancer prevention in HIV-infected women in low-income settings. These include:

  • firstly, the WHO recommendation offering HPV vaccine against HPV 16 and 18 to girls at ages 9–14 naïve to the targeted types;
  • secondly, a “screen and treat” approach, in which access to Visual Inspection with, 3-5% acetic acid (VIA) or if possible HPV testing followed soon or immediately by treatment of detected precancerous lesions;
  • thirdly, that “once a woman has been screened negative for pHR/HR HPV testing, she should not be rescreened for at least 5 years, but should be rescreened within ten”,
  • fourthly, that HIV-infected women be screened within 3 years if tested negative by VIA or cytology
  • lastly, that HIV-infected women embark on Highly active antiretroviral therapy (HAART) regardless of WHO clinical stage or CD4 count.

Eastern Africa, where cervical cancer is the most frequent type of cancer is also the region burdened with the world’s highest prevalence rates of HIV together. This overhaul in the global landscape of cervical cancer prevention is likely to have a significant impact on HIV-infected Kenyan women. With an estimated adult HIV prevalence of 5.6%, there are 1.2 million people living with HIV in Kenya. More than 75% of Kenyans live in rural areas, and, in recent years, HIV prevalence in rural areas has begun to reach levels estimated within urban setting.

Kenya has made a marked commitment to combat both HIV as well as the cervical cancer, which is the second most prevalent cancer in the country. However, there is a scarcity of data on the distribution of HPV genotypes, especially in the HIV positive population with abnormal cytology and ICC despite the current roll out of the quadrivalent vaccine and the commercialization of the nonavalent vaccine, containing additional HPV types HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antigens. Knowledge of the HPV genotype distribution data in cancer cases are indispensable for predicting the local impact of vaccination.

Notwithstanding a successful vaccination program, older women ineligible for vaccines, along with vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. Currently, there is limited data on the oncogenic potential of pHR HPV genotypes HIV-infected women. In addition, there is a lack of data on synergistic potential HR/HR HPV genotypes coinfections in HIV-infected women with abnormal cytology. Knowledge of particular combinations of HPV types, which are risk factor for the persistence and progression of cervical neoplasia, could be helpful for management of cervical lesions and clinical prediction of the outcome of HPV infections.

Furthermore, there is a dearth of studies from sub Saharan Africa on the association between BV and HPV and/or CIN. In light of its prevalence estimates ranging from 20 % to 50 %, the elucidation of HIV, HPV and BV interactions with one another is of utmost public health interest. Given the scarcity of resources, screening programs will need to be tailored to the human, financial resources and health profile of Kenya. This warrants the identification of most at risk HIV infected women who would benefit from a more regular follow up than once every three years as recommended by the WHO.

Aim:

This thesis purports to inform primary and secondary cervical cancer prevention programs within the framework of HIV preventive and care management in Kenya within a high BV setting.

Methodology:

The articles within this thesis employed cross sectional designs to explore the epidemiology of pHR/HR HPV genotypes and CIN 2 + in HIV-infected women in Kenya. A systematic review and meta-analysis was performed to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC. One systematic review was undertaken to examine the extent, range, and nature of research activities summarize research findings, and identify gaps in the existing literature on 1) the epidemiological association between HAART and HPV, cervical dysplasia and ICC.

Results:

Pooled prevalence of pHR/HR HPV genotype in Kenya

The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC, respectively (42% (95%CI: 35%-49%) versus 35% (95%CI: 25%-45%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between FSW

compared to non-FSW in women with both normal and abnormal cytology. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35, 21% (21 %; 95%CI: 18%-25%) and in women with ICC, HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%).

Risk factors for pHR/HR HPV genotypes:

Statistically significant associations between CD4 counts <200 cells/μl and multiple HPV prevalence, adjusted for age were also noted (OR = 3.7; 95 CI: 1.2–12.1; p = 0.03) and HPV53 (OR = 4.4, 95 % CI: 1.4–13.6; p = 0.01). BV was not significantly associated with pHR/HR HPV genotypes. A multivariate analysis adjusting for age, CD4 count and HPV co-infections suggested the presence of HPV 31 as a predictor of CIN 2+ (adjusted OR:4.9; p=0.04; CI:1.0-22.6).

ART

Our findings suggest that HAART increases CD4 count, which in turn is associated with lower HR HPV prevalence. HAART decreases incidence of CIN 2 and CIN 3, particularly in women with low CD4 count. The scarce data on HAART and ICC is inconclusive.

Conclusion:

Given the relatively high prevalence of non HPV 16 and HPV 18 in HIV infected women with abnormal cytology and ICC, a regular follow up in this population may be warranted. The cervical carcinoma genesis potential of HPV 53 as a stand-alone genotype and its high prevalence in HIV infected women suggests the need for affordable point of care nucleic acid amplification methods to detect pHR HPV genotypes throughout Kenya.

The 2014 WHO guideline to screen HIV infected women within three years may be more effective if BV becomes an integral component of cervical cancer prevention. A screening triage for more regular follow up for FSW, unvaccinated women, HIV + women irrespective of the CD4 count is warranted.

The lack of statistically significant associations observed in the systematic review between duration of ART intake and reduction of CIN 2+, in women initiating ART at an earlier CD4 count initiation suggests the importance of continued follow up with cervical cytological and/or histological screening, even after ART has been initiated and immune function restored.

The potential synergistic interactions between cervical disease, BV begs for an integrative cervical cancer prevention framework. In light of earlier ART initiation and decentralization of HIV care, there are opportunities for a more regular cervical screening program provided that front line nurses are better equipped to deal with challenges.

Authors & affiliation: 
Sonia S. Menon - Supervisors: Prof. dr. Davy Vanden Broeck and Prof. dr. Steven Callens
Staff Members: 
Published In: 
ICRH Monographs
Publication date: 
Monday, April 23, 2018