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Automated Raman spectral Cytology for detection of human papillomavirus (HPV) infection and cervical pre-cancer (ARC-HPV)

Dr Shiyamala Duraipandian, Marie Sklodowska-Curie Fellow

From: 2016-01-18 to 2018-01-25

Summary

Cervical cancer is the 4th most common cause of cancer death in women worldwide and the 7th most common cause of cancer death in females in Europe. Human papillomavirus (HPV) infection is very common in sexually active men and women. More than 100 different strains of HPVs have been identified and 14 of them (i.e., HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) are considered as high risk.  Most HPV infections (~90%) will self-resolve in two years but high risk HPV infection can cause chronic and persistent cellular changes. Persistent high-risk HPV infection can lead to pre-cancer (i.e., low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL)) and cancer. Cervical cancer can be prevented if it can be identified at an early stage. HPV vaccines can protect against the main high-risk HPV types, HPV 16 and 18, but they do not protect against all the high risk HPV types that can cause cervical cancer. Hence, regular cervical screening is still necessary.

The Pap test is the current test for identifying abnormalities in the cervix. In the Pap test, the cells are scraped from the cervix and examined for the presence of pre-cancer changes (LSIL and HSIL). However, this standard cytology method depends on visual assessment and is highly subjective with low sensitivity. Currently HPV testing is also performed on LSIL and HSIL cases and although this test has good sensitivity, its specificity is poor. Also, a positive HPV test result just indicates the presence of HPV DNA but does not indicate if the HPV infection is transient or persistent. 

Thus, there is an unmet clinical need to develop new methods with good sensitivity and specificity to objectively identify patients who are at high risk of developing cervical cancer.

The overall objective of this MSCA project was to develop new methods based on Raman spectroscopy for probing biochemical changes associated with high risk HPV infection and dysplasia in cervical cells collected during routine Pap smear screening. During the project, a comprehensive Raman spectral library containing high-quality Raman spectra measured from cervical samples of >400 patients was established. HPV DNA (Cobas 4800 HPV test) and HPV mRNA testing (APTIMA HPV test) was also carried out on all samples. A chemometric model was developed that could predict high-risk HPV infection and pre-cancer stage and most importantly could distinguish between persistent and transient HPV infection.  In addition to training through research, the MSCA fellow was trained in transferable skills such as project management, communication skills, networking, ethics, gender equality and IPR management.

Intersectoral transfer of knowledge was provided through a secondment at Dansk Fundamental Metrologi (DFM), Denmark.  This allowed the researcher to experience working in a non-academic environment which has been very beneficial for her career development.  At the end of the secondment, the researcher was offered a permanent Staff Scientist position at DFM.

Acknowledgement

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 661398