Cervical-vaginal cells, collected using conventional smears or liquid-based samples are the gold-standard for the detection of cervical HPV infection and cervical precancer. However, there are circumstances in which other types of samples are more informative or feasible, though as yet less well validated, than cervical samples.
Our group is working with samples from the cervix, the oral cavity and tonsils, and urine. Urine samples are being used to monitor the effectiveness of nationwide HPV vaccination in Bhutan (start: 2010) and Rwanda (start: 2011) in young women who may have initiated sexual activity but are often reluctant to accept a gynaecological examination for the collection of cervical cells. In 2013-14, we performed two school-based HPV urine surveys; 973 female students were recruited in Bhutan and 912 in Rwanda (1) (median age: 19). Participants self-collected a first-void urine sample using a validated protocol. HPV prevalence was obtained using two PCR assays that differ in sensitivity and type spectrum, namely GP5+/GP6+-PCR and E7-MPG. 92% students in Bhutan and 43% in Rwanda reported to have been vaccinated at age 14-18.
In Rwanda, HPV6/11/16/18 prevalence was lower in vaccinated than in unvaccinated students (prevalence ratio, PR=0.12, 95% confidence interval, CI: 0.03-0.51 by GP5+/GP6+, and 0.45, CI: 0.23-0.90 by E7-MPG). For E7-MPG, cross-protection against 10 high-risk types phylogenetically related to HPV16 or 18 was of borderline significance. In Bhutan, HPV6/11/16/18 prevalence by GP5+/GP6+ was lower in vaccinated than in unvaccinated students but CIs were broad. The Study of natural history of human Papillomavirus infection and precancerous Lesions In the Tonsils (SPLIT) will include 700 age-stratified individuals who underwent tonsillectomy for benign diseases in selected University Hospitals across France (2). SPLIT’s preliminary findings are reported elsewhere in this conference (3).
Our urine surveys highlight progresses in the standardization and accuracy of HPV detection in urine and its usefulness to monitor HPV vaccination. Conversely, the role of HPV testing in urine for cervical screening purposes is still unclear and self-collected cervical samples may provide a more acceptable and less demanding (from a laboratory view point) type of sample. HPV testing in oral cells is also a useful in epidemiological tool but the extent to which it can inform on HPV infection in the tonsils (from which most of HPV-associated cancers of the head and neck arise) is yet unclear.
[(1) Franceschi S, Umulisa MC, Tshomo U, Gheit T, Baussano I, Tenet V, Tshokey T, Gatera M, Ngabo F, Van Damme P, Snijders PJF, Tommasino M, Vorsters A and Clifford GM. Urine testing to monitor the impact of HPV vaccination in Bhutan and Rwanda. Int J Cancer 2016; submitted.
(2) Franceschi S, Combes JD, Dalstein V, Caudroy S, Clifford GM, Gheit T, Tommasino M, Clavel C, Lacau St Guily J, Birembaut P. Deep brush-based cytology in tonsils resected for benign diseases. Int J Cancer 2015;137: 2994-9.
(3) Combes JD, Dalstein V, Clifford GM, Gheit T, Tommasino M, Clavel C, Lacau St Guily J, Franceschi S. Study of HPV and precancerous lesions in the tonsils (“SPILT”): preliminary results. Abstract EUROGIN 2016, June 15-18 2016, Salzburg, Austria.]