A Study Comparing the Stability for Human Papillomavirus Testing of Three Dry Vaginal Self-samples Taken by Women Attending a Colposcopy Clinic

Background Cervical cancer is caused by persistent infection with high risk human papillomavirus types (Hr-HPV) but can be prevented if detected at an early stage. Prevention through routine cervical screening is traditionally done with liquid-based cytology sampling where the cells collected by clinicians are examined to identify abnormal features. Another method is HPV testing performed on the same liquid-based samples as for cytology. HPV DNA testing is more sensitive, but less specific, than cytology for cervical screening and both tests are broadly acceptable to women (Forrest, McCaffery et al. 2004; Waller, McCaffery et al. 2006; Szarewski, Cadman et al. 2009). Although clinician-taken samples are the gold standard, self-sampling may be a useful alternative. HPV DNA testing using self-collected (SC) samples has been shown to have acceptable sensitivity and specificity for HPV testing compared to samples taken by clinicians (Petignat, Faltin et al. 2007; Szarewski, Cadman et al. 2007; Arbyn, Verdoodt et al. 2014). A high level of concordance between self and clinician sample for HPV DNA detection of 0.87 (95% Confidence Intervals (CI), 0.82-0.91) was shown in Petignat's systematic review and meta-analysis (Petignat, Faltin et al. 2007). HPV DNA testing is well established but newer HPV testing technologies are available and emerging.

HPV DNA testing has most commonly been performed on cervical samples collected in a liquid medium (generally Specimen Transport Medium (STM) or PreservCyt). However, this is not ideal for home SC samples because there are often restrictions on postage of biological samples in liquid, risks (although low) pertaining to the transport medium itself and issues around refrigeration of the liquid. The removal of the necessity for a liquid transport medium (and especially any subsequent refrigeration) would greatly improve the accessibility of SC sampling and reduce costs. This would also increase the potential for cervical screening in those areas where there may be logistical difficulties such as lack of regular, frequent postal collections or refrigerated storage facilities.

There have been several studies which have investigated dry sample collection for HPV DNA detection (Shah, Daniel et al. 2001; Krech, Castriciano et al. 2009; Feng, Cherne et al. 2010; Cerigo, Coutlee et al. 2012; Darlin, Borgfeldt et al. 2013; Eperon, Vassilakos et al. 2013). However, the differing methodologies and requirements for refrigeration have restricted the generalisability of the results. They have also not addressed the question of how long the sample on the dry collection device would remain viable, especially under higher temperatures.

Rationale and Risks/Benefits Evidence increasingly suggests that, at least in temperate climates, HPV DNA testing from a SC sample using a dry swab provides similar sensitivity to a wet swab (where the SC sample is placed in liquid specimen transport medium) (Wolfrum, Koutsky et al. 2012). Dry transport could make HPV DNA testing from SC samples more accessible and widely available. In the UK for example, postal packaging is simplified when no liquid is involved. HPV primary screening is being explored in clinical trials and even being introduced into some screening programmes. In the Netherlands for example SC HPV DNA testing within the primary screening programme is planned for introduction for non-attenders in 2016 (Rijksinstituut voor Volksgezondheid en Milieu 2014).

The rationale of this stability study is to ascertain whether SC samples kept under dry conditions will still be useful if left for a period of time in warm conditions. This would be of particular use in the many low and middle income countries where cervical cancer incidence and mortality are highest. These countries have frequently found it very difficult to set up national cervical screening programmes due to lack of infrastructure, access to efficient refrigeration and a postal service.