Human papillomavirus infection, cervical cancer and the less explored role of trace elements

Abstract

Cervical cancer is an aggressive type of cancer affecting women worldwide. Many affected individuals rely on smear tests for the diagnosis, surgery, chemotherapy, or radiation for their treatment. However, due to a broad set of undesired results and side-effects associated with the existing protocols, the search for better diagnostic and therapeutic interventions is a never-ending pursuit. In the purview, the bio-concentration of trace elements (copper, selenium, zinc, iron, arsenic, manganese, and cadmium) is seen to fluctuate during the occurrence of cervical cancer and its progression from pre-cancerous to metastatic nature. Thus, during the occurrence of cervical cancer, the detection of trace elements and their supplementation will prove to be highly advantageous in developing diagnostic tools and therapeutics, respectively. This review provides a detailed overview of cervical cancer, its encouragement by human papillomavirus infections, the mechanism of pathology, and resistance. Majorly, the review emphasizes the less explored role of trace elements, their contribution to the growth and inhibition of cervical cancer. Numerous clinical trials have been listed, thereby providing a comprehensive reference to the exploration of trace elements in the management of cervical cancer.

Keywords: Cervical cancer; HPV; chemotherapy; diagnosis; trace elements.

Fig. 1

Anatomy of healthy cervix and the cancerous tissue showing the stages early and late stage IB, and stage IIB

Fig 2

Human Papilloma Virus. Representation of the structure (a), and the genome organization (b)

Fig. 3

Histological considerations during cervical cancer graded as cervical intraepithelial neoplasia (CIN) and squamous intraepithelial lesion (SIL) depicting (1) the healthy squamous epithelium of the cervix, and observable changes during cancer including (2) the infection by human papillomavirus (HPV) with the episomal viral DNA in the nucleus of the cell, (3) cells expressing the early and late genes, (4) cells overexpressing the oncoproteins E6 and E7, and (5) the metastatic cancer with the complete integration of the viral DNA in the nucleus of the cells

Fig. 4

The mechanism of human papillomavirus (HPV) infection of the cervical cells, followed by the overexpression of the oncoproteins E6 and E7, leading to the derangement of the normal protective mechanisms of the cervical cells, resulting in the uncontrolled cell proliferation and resistance to cell death, termed as cervical cancer

Fig. 5

Transmission electron microscopic image of ZnO quantum dots. Reproduced under CC BY 4.0 from [232], Frontiers in Pharmacology

Fig. 6

Transmission electron microscopic images of fluorescent gold-nanocrystals-silica hybrid (FLASH) nanocomposites. Scale bar—50 nm. Reproduced from [251] with permission from American Chemical Society (ACS)

Fig. 7

Microscopic images of Fe₅C₂-based nanoparticles. a Transmission electron microscopy (TEM) and b high-resolution TEM image of Fe₅C₂ nanoparticles, c TEM image of Fe₅C₂-GOD, and d Fe₅C₂-GOD@MnO₂ nanocatalysts. Reproduced from [254] with permission from American Chemical Society (ACS)