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Cervical cancer is more common in Sub-Saharan Africa (SSA) compared to developed countries, with persistent genital high-risk HPV (HR-HPV) infection identified as the cause. However, other factors contributing to this gap remain unclear. This review explores the potential role of cervicovaginal microbiota (CVM) in genital HPV infection and cervical cancer development among women in SSA. Many women of African descent, including those from SSA, lack lactobacilli dominance in their CVM, which is considered a biomarker of cervicovaginal health. Published literature has associated Lactobacillus-dominated CVM with a lower risk of HPV infection and cervical cancer. The converse is true for women with high diversity non-Lactobacillus-dominated CVM and bacterial vaginosis, the most common form of vaginal disorder. However, findings on the relationship between specific bacterial abundance and cervical disease severity are inconsistent and inconclusive due to differences in study design, study population, sampling, and potential confounders. Thus, there is a need to form consensus to advance research on CVM and HPV-associated cervical disease. Despite the exact mechanisms by which CVM influence HR-HPV persistence and cervical carcinogenesis being unknown, the backbone of the mechanisms appears to be mediated in part by the following: cervicovaginal dysbiosis, elevated vaginal pH, high ratio of L-to-D-lactic acid, cohesive biofilm formation, chronic inflammation, and immune dysregulation. Consequently, these promote cellular proliferation, genetic instability, and evasion of immune surveillance. This review calls for larger, prospective studies to unravel causal links, identify protective features, and integrate CVM interventions into HPV and cervical cancer prevention strategies in SSA.

Summary: Background: Hyperthermia is a well-accepted cancer therapy. Microwaves provide a very precise, targeted means of hyperthermia and are currently used to treat plantar warts caused by cutaneous-infective human papillomaviruses (HPVs). Other HPV genotypes infecting the anogenital mucosa cause genital warts or preneoplastic lesions or cervical cancer. Effective, non-ablative therapies for these morbid HPV-associated lesions are lacking. Methods: The molecular consequences of microwave treatment were investigated in in vitro cultured three-dimensional HPV-positive cervical tumour tissues, and tissues formed from HPV-infected normal immortalised keratinocytes. Microwave energy delivery to tissues was quantified. Quantitative reverse transcriptase PCR was used to quantify mRNA expression. Immunohistochemistry and fluorescence immunostaining was used to assess protein expression. Findings: Microwave energy deposition induced sustained, localised cell death at the treatment site. There was a downregulation in levels of HPV oncoproteins E6 and E7 alongside a reduction in cellular growth/proliferation and induction of apoptosis/autophagy. HSP70 expression confirmed hyperthermia, concomitant with induction of translational stress. Interpretation: The data suggest that microwave treatment inhibits tumour cell proliferation and allows the natural apoptosis of HPV-infected cells to resume. Precision microwave delivery presents a potential new treatment for treating HPV-positive anogenital precancerous lesions and cancers. Funding: Funding was through an Innovate UK Biomedical Catalyst grant (ID# 92138-556187), a Chief Scientist Office grant (TCS/19/11) and core support from Medical Research Council (MC_ UU_12014) core funding for the MRC-University of Glasgow Centre for Virus Research.

Abstract Background An infection with high-risk human papillomavirus (HPV) is the obligatory aetiological factor for the development of cervical cancer. In Switzerland, the prevention strategy for cervical cancer is based on primary prevention via HPV vaccination and secondary prevention with an opportunistic screening programme for precancerous lesions. Vaccination is recommended to 11–26 years old male and female persons. The objective of the study was to assess the epidemiological impact on cervical cancer of switching from the currently implemented programme with the 4-valent vaccine to the 9-valent vaccine, in an 11–26 years old gender-neutral vaccination programme in Switzerland. Methods A previously validated dynamic transmission model of HPV infections was adapted and calibrated to the Swiss setting assuming an 80% coverage rate in HPV-vaccination and lifelong vaccine type-specific protection. A gender-neutral vaccination programme (males and females) for 11–26 years old with a 9-valent HPV vaccine was compared with the current 11–26 years old gender-neutral 4-valent vaccination programme. Sensitivity analyses were conducted in order to test the impact of lower vaccination coverage rates and a shorter duration of protection on the model outcomes. Results In Switzerland, a 9-valent gender-neutral vaccination programme would result in an additional prevention of 2979 cervical cancer cases, 13,862 CIN3 and 15,000 CIN2 cases, compared with the 4-valent gender-neutral vaccination programme over 100 years. These additional disease cases avoided would correspond to a 24, 36 and 48% cumulative incidence decrease in cervical cancer, CIN3 and CIN2 cases, respectively. It would also prevent additional 741 cervical cancer-related deaths over 100 years. A substantial additional reduction in cervical cancer and precancerous lesions burden is still observed when varying the vaccination coverage rate from 30 to 60% or reducing the duration of protection from lifelong to 20 years. Conclusions The switch to the 9-valent vaccine in Switzerland to prevent cervical diseases showed an important contribution in terms of public health impact compared with the 4-valent vaccine in an 11–26 years old gender-neutral population, even with very conservative assumptions such as low coverage rates or low duration of protection and limiting analysis to only cervical disease.

The investigation of differentially expressed genes (DEGs) and their interactome could provide valuable insights for the development of markers to optimize cervical intraepithelial neoplasia (CIN) screening and treatment. This study investigated patients with cervical disease to identify gene markers whose dysregulated expression and protein interaction interface were linked with CIN and cervical cancer (CC). Literature search of microarray datasets containing cervical epithelial samples was conducted in Gene Expression Omnibus and Pubmed/Medline from inception until March 2021. Retrieved DEGs were used to construct two protein-protein interaction (PPI) networks. Module DEGs that overlapped between CIN and CC samples, were ranked based on 11 topological algorithms. The highest-ranked hub gene was retrieved and its correlation with prognosis, tissue expression and tumor purity in patients with CC, was evaluated. Screening of the literature yielded 9 microarray datasets (GSE7803, GSE27678, GSE63514, GSE6791, GSE9750, GSE29570, GSE39001, GSE63678, GSE67522). Two PPI networks from CIN and CC samples were constructed and consisted of 1704 and 3748 DEGs along 21393 and 79828 interactions, respectively. Two gene clusters were retrieved in the CIN network and three in the CC network. Multi-algorithmic topological analysis revealed PCNA as the highest ranked hub gene between the two networks, both in terms of expression and interactions. Further analysis revealed that while PCNA was overexpressed in CC tissues, it was correlated with favorable prognosis (log-rank P=0.022, HR=0.58) and tumor purity (P=9.86 × 10-4, partial rho=0.197) in CC patients. This study identified that cervical PCNA exhibited multi-algorithmic topological significance among DEGs from CIN and CC samples. Overall, PCNA may serve as a potential gene marker of CIN progression. Experimental validation is necessary to examine its value in patients with cervical disease.

The purpose of this study was to investigate the incidence of cervical disease in women of different age groups in the Republic of Sakha (Yakutia). Materials and Methods: The cytological material of the cervix of 7,600 women aged between 18 and 88 years was analyzed in the laboratory of pathomorphology, histology and cytology. The material of the cytological study consisted of smears of cervical mucosa and the cervical canal, stained according to the method of Romanovsky-Giemsa. The study was conducted with subjects grouped according to age: Group 1 (18-29), Group 2 (30-44), Group 3 (45-59), and Group 4 (60-74). Results: According to the results of cytological analysis, inflammatory diseases of the cervix uteri were diagnosed in 4,629/61% cases. Among age groups, the highest rate of inflammatory diseases of the cervix uteri was registered in Group 1 and Group 2. Benign cervical lesions were found in 563/7.4% cases with the highest incidence in Groups 1 and 2. The most frequently diagnosed pathology was squamous cell metaplasia with maximum frequency in Group 2 and Group 1. Cervical intraepithelial neoplasia (or dysplasia) (CIN) was detected in 359/4.7% cases. CIN I, CIN II and CIN III were registered in 220/61.3%, 84/24.5%, and 38/10.6% women, respectively. At the same time, the maximum frequency of dysplasia was noted in Group 1 and Group 2. Thus, results obtained indicate a high incidence of cervical disease in women of reproductive age.

Objective: We report two patients with benign giant cervical polyps. Case Report: A 47-year-old multiparous woman complained of a protruding mass from her vagina for 6 months. On pelvic examination, there was a large cervical polyp measuring 7 × 2.5 cm arising from the endocervix. The polyp was excised by electrocauterization at the base. The pathological report revealed no evidence of malignancy in the polyp. A 45-year-old nulligravid woman suffered from menorrhagia for 2 months and a mass protruding from the vagina was noted for 10 days. On pelvic examination, there were two cervical polyps. One was 5 × 2 cm and arose from the posterior lip of the cervix and the other was 1 × 1 cm and arose from the right lateral lip. The polyps were excised by electrocauterization. The pathological report revealed benign cervical polyps. Conclusion: Giant cervical polyp is uncommon and malignancy has not been reported in the 11 cases in the literature. Excision was adequate for these lesions.