Infection with high-risk genotypes of human papillomavirus and cervical cytological findings among kidney transplant recipients in Kenya: a single centre experience

Background: High-risk human papillomavirus (hrHPV) infection is linked with uterine cervix premalignant lesions and invasive carcinomaof the uterine cervix. Methods: Descriptive cross sectional study carried out among female kidney transplant (KTx) recipients in Kenyatta National Hospital, Nairobi-Kenya. We studied the risk factors for acquisition of hrHPV, examined cervical cytology and assayed for 14 hrHPV DNA using Cervista® HPV HR test and Cervista® MTA (Hologic®) automated platforms. Results: The 14-hrHPV genotypes assayed were 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 and the prevalence rate was 31.25 % (10/32). Abnormal cervical cytology was noted in 4/32 (12.5%) and included low-grade squamous intraepithelial lesion (2/32), atypical squamous cells of undetermined significance (1/32) and atypical glandular cells (1/32). The average age was 41.9 years with mean age at first coitus being 20.4 years. Majority of the women 20(62.5%) were married while 8(25%) were single. About 18(56.3%) had only one sexual partner. About 20% of women were nulliparous and 4(12.5%) had a parity of five. Duration since transplantation ranged between 1-21 years. Conclusions: The burden of hrHPV and abnormal cervical cytology in our study seemed lower than that reported elsewhere andeven in general population. This study may form basis for further studies about HPV infections and carcinoma of the uterine cervixamong the kidney allograft recipients in our setting. Keywords: Cervical carcinoma; kidney transplant recipients; high risk Human Papillomavirus

A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874

Symptoms experienced by study subjects within one month of starting Lopimune treatment.

<p>Symptoms experienced by study subjects within one month of starting Lopimune treatment.</p

Cervista® HPV test, cytology and PCR HPV genotype analysis.

<p>HPV titre is indicated by the height of the bar graph above the cut off with the Y axis representing the fold over zero (FOZ) ratio of sample or control divided by the no target control signal. The cytology status is indicated by colour and shading with the HPV type shown above the bar. (A) Represents the results before treatment with lopinavir; (B) Represents results after 4 and (C) 12 weeks after treatment.</p

Changes in cytology and HPV results between baseline and 3-month visits following Lopimune treatment.

<p>Changes in cytology and HPV results between baseline and 3-month visits following Lopimune treatment.</p

Patient screening, testing and management flow chart used for the study.

<p>Patient screening, testing and management flow chart used for the study.</p

Participant characteristics at study baseline.

<p>Participant characteristics at study baseline.</p