Human papillomavirus infection in Bhutan at the moment of implementation of a national HPV vaccination programme

BACKGROUND: Cervical cancer is the most common female cancer in Bhutan, the first low/middle-income country to implement a national human papillomavirus (HPV) vaccination programme. METHODS: To provide a robust baseline for future evaluations of vaccine effectiveness, cervical cell specimens were obtained from 2,505 women aged 18–69 years from the general population, and biopsies from 211 cervical intraepithelial neoplasia grade 3 (CIN3) and 112 invasive cervical cancer (ICC) cases. Samples were tested for HPV using GP5+/6+ PCR. RESULTS: Among the general population, HPV prevalence was 26%, being highest (33%) in women ≤24 years, but remaining above 15% in all age-groups. Determinants of HPV included age, marital status, and number of sexual partners. Among the eight percent with cytological abnormalities, 24 CIN3 and 4 ICC were histologically confirmed. Even after additional testing with a sensitive E7 PCR, no infections with vaccine-targeted HPV types were detected in the few vaccinated women (n = 34) compared to 6% prevalence in unvaccinated women of similar age (p = 0 · 215). CONCLUSION: Based upon type-specific prevalence among biopsies, at least 70% of ICC in Bhutan are theoretically preventable by HPV16/18 vaccination, but screening programmes should be expanded among older women, who have an important underlying burden of CIN3 and ICC

Gender‐neutral HPV elimination, cervical cancer screening, and treatment: Experience from Bhutan

Cervical cancer is preventable and also curable when detected early and treated adequately, yet it remains a leading cause of morbidity and mortality among women. In Bhutan, cervical cancer is the most common cancer among women. Bhutan was the first country among the low- and middle-income economies to have instituted a national HPV vaccination program, in 2010, and has achieved >90% coverage. In 2019, Bhutan launched a cervical cancer elimination flagship program well ahead of WHO's launch of the global strategy for accelerated elimination of cervical cancer. Bhutan initiated vaccination of adolescent boys and adopted a gender-neutral vaccination program beginning September 2020 through its well-established network of primary healthcare centres. The flagship program aims to screen women aged 30-69 years with HPV testing using liquid-based cytology (LBC) as triaging for screen positive women. For women aged 25-29 years, LBC will be continued as per American Society of Colposcopy and Cervical Pathology guidelines. Colposcopy and treatment will be performed in camps to decrease loss of follow up of screen positive women. This program is also expected to improve early diagnosis of cervical cancer and provide timely and adequate cancer treatment and palliative care services. This article reviews the progress made and the challenges facing the 2030 cervical cancer elimination targets in Bhutan

Evaluation of the performance of Human Papillomavirus testing in paired urine and clinician-collected cervical samples among women aged over 30 years in Bhutan

Abstract Background Urine sampling may offer a less invasive solution than cervical sampling to test for human papillomavirus (HPV) for HPV vaccine impact monitoring. Methods Paired samples of urine and exfoliated cervical cells were obtained for 89 women with history of high-risk (HR) HPV-positive normal cytology in Bhutan. Urine sampling protocol included self-collection of first-void urine immediately into a conservation medium and procedures to optimize DNA yield. Colposcopical abnormalities were biopsied. Two HPV assays were used: a multiplex type-specific PCR (E7-MPG) and a less analytically sensitive GP5+/6+ PCR followed by reverse line blot. Results HPV positivity for 21 types common to both assays was similar in urine and cells by E7-MPG (62.9% and 57.3%, respectively, p = 0.32) but lower in urine by GP5+/6+ (30.3% and 40.4%, p = 0.05). HPV6/11/16/18 positivity did not significantly differ between urine and cells by either assay. Sensitivity of urine (using cells as gold standard) to detect 21 HPV types was 80% and 58% for E7-MPG and GP5+/6+, respectively, with specificity 61% and 89%. HPV type distribution in urine and cells was similar, regardless of assay. The 5 detected CIN3+ were HR-HPV positive in cells by both assays, compared to 4 and 3 by E7-MPG and GP5+/6+, respectively, in urine samples. Conclusion For the monitoring of vaccine impact, we demonstrate validity of a urine sampling protocol to obtain HPV prevalence data that are broadly comparable to that from cervical cells. However, detection of HPV in urine varies according to assay sensitivity, presumably because low level infections are frequent

Human papillomavirus genotype and viral load agreement between paired first-void urine and clinician-collected cervical samples

Abstract: The performance and acceptability of first-void urine as specimen for the detection of HPV DNA in a Belgian referral population was evaluated using an optimized sample collection and processing protocol. One hundred ten first-void urine and cervical samples were collected from 25- to 64-year-old women who were referred for colposcopy (JanuaryNovember 2016). Paired samples were analyzed by the Riatol qPCR HPV genotyping assay. Acceptability data were gathered through questionnaires (NCT02714127). A higher high-risk HPV DNA prevalence was observed in first-void urine (n\u2009=\u200976/110) compared to cervical samples (n\u2009=\u200973/110), with HPV31 and HPV16/31 being most prevalent correspondingly. For both any and high-risk HPV DNA, good agreement was observed between paired samples (Cohens Kappa of 0.660 (95% CI: 0.4860.833) and 0.688 (95% CI: 0.5420.835), respectively). In addition, significant positive correlations in HPV copies (per microliter of DNA extract) between paired samples were observed for HPV16 (rs\u2009=\u20090.670; FDR (false discovery rate)-adjusted p\u2009=\u20090.006), HPV18 (rs\u2009=\u20090.893; FDR-adjusted p\u2009=\u20090.031), HPV31 (rs\u2009=\u20090.527; FDR-adjusted p\u2009=\u20090.031), HPV53 (rs\u2009=\u20090.691; FDR-adjusted p\u2009=\u20090.017), and HPV68 (rs\u2009=\u20090.569; FDR-adjusted p\u2009=\u20090.031). First-void urine sampling using a first-void urine collection device was preferred over a clinician-collected cervical sample. And mostly, first-void urine sampling at home was favored over collection at the clinic or the general practitioners office. First-void urine sampling is a highly preferred, non-invasive method that ensures good agreement in HPV DNA (copies) with reference cervical samples. It is particularly interesting as a screening technique to reach non-participants, and its clinical performance should be further evaluated