Human Papillomavirus (HPV)

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Human Papillomavirus (HPV) infection is the most common sexually transmitted infection (STI). More than half of the people sexually active have been infected by HPV. Human Papilloma viruses constitute a group of approximately 150 related viruses. More than 40 of these viruses are spread through sexual contact (oral, vaginal and anal). High risk sero-types of HPV are responsible for many forms of cancer, including cervical cancer (1). Most people do not realize they are infected, but do transmit the infection to others.

 

Symptoms of Human Papillomavirus (HPV)

HPV infection, or infection with Human Papillomavirus, is a very common STI. Nearly all men and women who are sexually active become infected at a certain point in time. However, this STI often does not evoke any symptoms as the immune system combats the HPV infection. For that reason, many people who are infected with HPV are not aware of it. Yet the longer HPV is present in the body, the more damage it can inflict.

  • High-risk HPV sero-types (HPV 16, 18, 31, and 45) can cause different types of cancer, including cervical cancer. Cervical cancer usually does not evoke any symptoms until evolved to an advanced stage. Advanced stages of cervical cancer are however far less curable, compared to initial HPV infections. For this reason, regular HPV testing and cervical cancer screening is important for women.
  • Other HPV-related cancers might also not cause any symptoms until they have evolved into an advanced stage. These cancers include certain cancers of the vulva, vagina, penis, anus, and oropharynx (part of the throat).
  • Low-risk HPV sero-types can cause genital warts. Genital warts are small bumps in the genital area. Warts can appear within weeks or months after the sexual contact through which they were transmitted. All genital warts are caused by a HPV infection.
  • RRP is a rare condition which causes warts to grow inside the throat, and is also caused by HPV infection. The warts can sometimes block the airway, causing the patient’s voice to get hoarse or causing trouble breathing.

Prevention of HPV infection

HPV infection can be prevented by abstinence, monogamous relationships, condom-use during sexual contact, or by vaccination. When using a condom, genital areas that are not covered by the condom, can however still be infected. Vaccines are available for boys and girls aged 11 and 12 years. Catch-up vaccines are recommended for males through age 21 and for females through age 26, if they did not get vaccinated when they were younger. In addition, screening programs for women aged 21 to 65 years old can prevent cervical cancer. 

 

Detection of HPV infection

HPV infection can be detected by the analysis of a swab specimen (cervical sample for women or urethra sample for men), self-collected vaginal swabs, or voided urine. The urine sample for detection of HPV preferably consists of first-void urine, or the first fraction of the urine stream. First-void urine contains a larger amount of DNA particles compared to midstream, allowing for an easier detection of HPV (2;6).

The first-voided urine needed for detection can easily be collected at home, for example using the Colli-Pee. This device guarantees capturing the first part of the urine stream, known as first-void urine, by blocking the inflow of the remaining urine. Blocking this inflow is very important since further urine collection would dilute the first-void sample. Home-based sampling with Colli-Pee in addition avoids intimate, and possibly uncomfortable, examinations. Colli-Pee also makes testing much easier for women, since there is no need for a vaginal swab.

 

Treating HPV detection

Currently there is no treatment for HPV infection. Yet the STI often clears by itself. According to the Centers for Disease Control and Prevention, the body’s immune system clears HPV naturally within two years for 90% of cases.

Sometimes an surgical operation is needed in order to take away part of the uterus. However, infected patients are usually not operated immediately after determiniaton of HPV infection but are followed up, to monitor potential cancer development. Due to monitoring a quick diagnosis and treatment are possible.

 

Consequences of HPV infection

HPV infection can cause cervical cancer (cancer on the cervix of women) and fertility problems. Other cancers caused by HPV are genital cancers (cancer of the vulva, vagina, penis, or anus) and oropharyngeal cancer, or cancer in the back of the throat. In some cases, HPV can also cause recurrent respiratory papillomatosis (RRP), a condition which causes warts to grow in the throat.

 

Novosanis' research on HPV and the Colli-Pee device

UAntwerp and Novosanis recently collaborated to conduct two clinical trials (BiR&D and IWT, 2015) to evaluate the performance of Colli-Pee™ in collecting urine for the detection of HPV versus regular urine collectors such as Multi-Collect™ (Abbott). It was concluded that urine collected using the Colli-Pee™ yielded a higher number of copies of HPV DNA compared to the Multi-Collect system and these findings were independent of collection time. We are also proud of our collaboration with WHO, a world renown organization, to carry out a clinical trial (WHO study, 2016) to investigate the impact of vaccination against HPV in Rwanda and Bhutan. This trial included an impressive sample size of 1885 girls, recruited either in Rwanda or Bhutan. Results from this study support the feasibility of urine surveys to monitor HPV vaccination and quantifies the effectiveness of the quadrivalent vaccine in women vaccinated after pre-adolescence.

Other studies carried out by Novosanis in collaboration with other parties, have compared the Colli-Pee™ to other self-sampling devices. The EVAH study (2015) and the ongoing research of the SESAM study compares the Colli-Pee™ to another self-sampling device called the Evalyn® brush, to clinician-based sampling (cytology & HPV test). HPV testing using the Colli-Pee showed to be more feasible, with a sensitivity and specificity similar to vaginal self-samplers and physician-taken smears.

Various proof of concept studies have been carried out to further investigate the compatibility of the Colli-Pee™ on various diagnostic assays. However, till date, these studies have only been carried out on smaller sample sizes. We look forward to investigate bigger samples in the future to strengthen our conclusions.

  • BD-Onclarity™ study: The BD Viper LT automated assay proved a similar performance with a higher throughput and minimal hands on time, using a small sample volume and fully integrated workflow. Colli-Pee™ collection device resulted in a higher analytic sensitivity.
  • Cepheid-Xpert® HPV study: a high correlation between human DNA quantities and a very high correlation for HPV 16 DNA quantities were found using both methods. These results are very encouraging to further investigate the performance of first-void collected, UCM preserved urine in combination with Xpert® HPV.
  • Roche-COBAS® HPV study: high positive correlations between Ct values of human DNA (GADPH and beta-globin) and very high positive correlations between Ct values of HPV 16 DNA were found. The compatibility of Colli-Pee™ collected, UCM preserved urine is very encouraging to further investigate possible applications. Sensitivity may significantly increase by modifying the internal threshold for first-void urine samples.
  • Genefirst-Papilloplex™ HR-HPV study: a good agreement was found between the three analytical methods for hDNA and hrHPV DNA, especially for HPV16 a very high positive correlation was found. Colli-Pee™ collected urine showed a higher analytical sensivity compared to urine cup collected urine. Future studies will focus on clinical cut-off determination and demonstration of assay performance in larger studies.

References:

  1. Goodman, et al. BMJ. 2015. PMID:26126623
  2. Vorsters, et al. Eur J Clin Microbiol Infect Dis. 2014. PMID: 24916950
  3. Pathak, et al. BMJ. 2014. PMID: 25232064
  4. Burroni, et al. J Med Virol. 2015. PMID: 25418873
  5. Ducancelle, et al. Arch Gynecol Obstet. 2014. PMID: 24622934
  6. Payan, et al. J Clin Microbiol. 2007. PMID: 17229868