Abstract
High-risk human papillomavirus (HPV) infection is the cause of almost all cervical cancers. HPV16 is one of the main risk subtypes. Although screening programs have greatly reduced the prevalence of cervical cancer in developed countries, current diagnostic tests cannot predict if mild lesions may progress into invasive lesions or not. In the current cross-sectional and longitudinal clinical study, we found that the HPV16 E7-specific T cell response in peripheral blood mononuclear cells of HPV16-infected patients is related to HPV16 clearance. It contributes to protecting the squamous interaepithelial lesion (SIL) from further malignant development. Of the HPV16 infected women enrolled (n = 131), 42 had neither intraepithelial lesion nor malignancy (NILM), 33 had low-grade SIL, 39 had high-grade SIL, and 17 had cervical cancer. Only one of 17 (5.9%) cancer patients had a positive HPV16 E7-specific T cell response, dramatically lower than the groups of precancer patients. After one year of follow-up, most women (28/33, 84.8%) with persistent HPV infection did not exhibit a HPV16 E7-specific T cell response. Furthermore, 3 malignantly progressed women, one progressed to high-grade SIL and two progressed to low-grade SIL, were negative to the HPV16 E7-specific T cell response. None of the patients with a positive HPV16 E7-specific T cell response progressed to further deterioration. Our observation suggests that HPV16 E7-specific T cell immunity is significant in viral clearance and contributes in protection against progression to malignancy.
Highlights
Cervical cancer is a malignant tumor that seriously threatens the life and health of women
In this study, using patient peripheral blood mononuclear cells (PBMCs) infected with HPV16, we compared the ability of ROP-16 E7 with a pool of HPV16 E7 overlapping peptides to simulate the specific T cell response against HPV16 E7
The purpose of this study was to evaluate the role of human papillomavirus (HPV) specific T cell immunity in the clinical outcome of HPV infected patients
Summary
Cervical cancer is a malignant tumor that seriously threatens the life and health of women. It is an accepted fact that high-risk human papillomavirus (HR-HPV) infection is the main risk factor for the occurrence, persistence, and development of cervical cancer [2]. Hybrid capture 2 (HC-2) or HPV-DNA typing combined with cytology examination are the diagnostic methods used to detect cervical cancer [3]. These methods cannot distinguish invasive lesions from noninvasive lesions, nor do they provide any prognostic value for patients. Only about 1% of women infected with HR-HPV will gradually develop cervical cancer [4, 5]. If the viral clearance mechanism exists, it may not be urgent for HPV-infected women to undergo surgery
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