Cervical Screening in North Sardinia (Italy): Genotype Distribution and Prevalence of HPV among Women with ASC-US Cytology

The assessment of human papillomavirus (HPV) genotype dynamics could support the adoption of more tailored preventive actions against cervical cancer. The aim of the study was to describe the prevalence of HPV infection, HPV genotype distribution, and the epidemiological characteristics of women with ASC-US cytology since the introduction of HPV-DNA testing in Sardinia (Italy), (March 2016–December 2020). Specimens were tested by RT-PCR for 14 high-risk HPV genotypes. A total of 1186 patients were enrolled, with a median (IQR) age of 41 (38–48) years. Of these women, 48.1% were positive for at least one HPV genotype; 311 (26.2%) women were vaccinated with a median (IQR) age of 38 (30/47) years. The percentage of prevalence of HPV-16, -31, -66, -56, and -51 was 36.3%, 18.7%, 11.9%, 11.4% and 10.7%, respectively. The highest prevalence of infection was found in women aged <41 years, and single women. Moreover, women aged >41 years (OR: 0.51, 95% CI: 0.31–0.86; p-value: 0.01), having parity (OR: 0.57, 95% CI: 0.34–0.96, p-value: 0.04), and higher educational level (OR: 0.39, 95% CI: 0.18–0.87; p-value: 0.02) were associated with a lower CIN2+ risk. We did not find a significant difference in terms of prevalence of HPV-16 infection between vaccinated and non-vaccinated (18.3% vs. 17.1%; p-value < 0.001). Our results support the adoption of nonavalent HPV-vaccine to prevent the most prevalent infections caused by HPV-16 and -31 genotypes and underscore the need of surveillance to implement tailored vaccination programs and preventive strategies.

Evidence of High-Risk Human Papillomavirus in Esophageal Cancer in East Azerbaijan Province, Northwest of Iran

Background. Human papillomavirus (HPV) is one of the most important viral agents associated with several classes of cancers in humans. The aim of this study was to investigate HPV in esophageal cancer in the East Azerbaijan province, northwest of Iran. Methods. 140 paraffin-embedded specimens of esophageal tissues were investigated using nested-polymerase chain reaction (nested-PCR) with primer designing for the L1 region of HPV genome. According to the pathological diagnosis, the samples were divided into two groups: 70 patients with esophageal cancer EADC (n = 35) and ESCC (n = 35) as the case group and those without tumour in esophagus tissue as a control (n = 70). Results. HPV DNA was isolated from 20 (28.57%) of the 70 paraffin-embedded tissue specimens of esophagus cancer. Of these, 6 cases (17.14%) of EADC and 14 cases (40%) of ESCC were positive. In contrast, all cases of the control group were negative for the HPV genome. Sequence analysis revealed that HPV types 16 and 18 are the most frequent ones identified in this study. Conclusion. The prevalence of HPV in esophageal cancer can vary depending on the geographical location and other factors. Based on the findings of this study, HPV infection may possibly have contributed to an increased risk of esophageal cancer in a group of patients in Tabriz.

Prevalence and distribution of human papillomavirus genotypes among women attending gynecology clinics in northern Henan Province of China

Background Human papillomavirus (HPV) infection can cause cervical and other cancers, including vulva, vagina, penis, anus, or oropharynx. However, in China's northern Henan Province, data on the prevalence and genotype distribution of HPV among women attending gynecology clinics is limited. This study aimed to investigate the current prevalence and genotype distribution of HPV among women attending gynecology clinics in northern Henan Province. Methods This study included 15,616 women aged 16–81 years old who visited the Xinxiang central hospital's gynecology department between January 2018 and December 2019. HPV DNA was detected by a conventional PCR method followed by HPV type-specific hybridization, which was designed to detect 17 high-risk HPV (HR-HPV) genotypes and 20 low-risk HPV (LR-HPV) genotypes. HPV prevalence and corresponding 95% confidence intervals (95% CI) were calculated using SPSS 18.0. Results The overall HPV prevalence was 19.7% among women in northern Henan Province. Single, double, and multiple HPV infections accounted for 13.7%, 4.3%, and 1.8% of the total cases. Most infections were caused by HR-HPV (71.8%), and single genotype HPV infection (13.7%) was the most common pattern. The most common HR-HPV genotype was HPV16 (4.3%), followed by HPV52 (3.5%) and HPV58 (2.0%). The most common LR-HPV genotype was HPV6 (1.4%), followed by HPV61 (1.1%) and HPV81 (1.1%). Conclusions HPV infection is high among women attending gynecology clinics in northern Henan Province. The highest prevalence was found in women less than 20 years old. In northern Henan Province, the 9-valent HPV vaccine is strongly recommended for regular immunization.

Development and testing of procedures for detecting HPV 6 and HPV 16 DNA in water samples

The present study aims to develop and test procedures for detecting the DNA of dangerous human papillomaviruses (HPV) types 6 and 16 in water samples. The conserved segments of HPV 6 L1 and HPV 16 L1 nucleic acid sequences were studied using bioinformatic methods with the help of the NCBI (National Center for Biotechnology Information) database and the BioEdit program. A total of 135 nucleic acid sequences of HPV6 L1 and 945 nucleic acid sequences of HPV16 L1 were examined. Five pairs of specific primers were developed for the identified conserved segments of nucleic acid sequences using specialized programs (PerlPrimer v.1.1.21, FastPCR 6.6, and Primer3Plus). In addition, several procedures for collecting samples from various water bodies located near Listvyanka settlement (Lake Baikal) were tested. The samples were subjected to comprehensive purification from insoluble particles and bacterial contamination to be tested for the presence of HPV DNA via PCR analysis using primers complementary to the nucleic acid sequences of HPV6 L1 and HPV16 L1. The conducted studies revealed HPV 6 and HPV 16 DNA in the water samples. Due to the use of the developed and tested procedures for collecting and examining samples from various water sources in the Baikal Natural Territory followed by a PCR analysis, it was possible to detect the presence of dangerous viruses. The proposed procedure of testing water samples for the presence of HPV can be useful in developing effective monitoring of water bodies and wastewater both in Baikal and other regions.

Mapping Human Papillomavirus, Epstein-Barr Virus, Cytomegalovirus, Adenovirus, And P16 In Laryngeal Cancer

Purpose: Apart from tobacco and alcohol, viral infections are proposed as risk factors for laryngeal cancer. The occurrence of oncogenic viruses including human papilloma virus (HPV) and Epstein-Barr virus (EBV), in laryngeal squamous cell carcinoma (LSCC) varies in the world. Carcinogenesis is a multi-step process, and the role of viruses in LSCC progression has not been clarified. We aimed to analyze the presence and co-expression of HPV, EBV, human cytomegalovirus (HCMV) and human adenovirus (HAdV) in LSCC. We also investigated if p16 can act as surrogate marker for HPV in LSCC. Methods: Combined PCR/microarrays (PapilloCheck®) were used for detection and genotyping of HPV DNA, real time-PCR for EBV, HCMV and HAdV DNA detection, and EBER in situ hybridization (EBER-ISH) for EBV detection in tissue from 78 LSCC patients. Additionally, we analyzed p16 expression with immunohistochemistry.Results: Thirty-three percent (26/78) of LSCC tumor samples were EBV positive, 9% (7/78) HCMV positive and 4% (3/78) HAdV positive. Due to DNA fragmentation, 45 samples could not be analyzed with PapilloCheck®; 9% of the remaining (3/33) were high-risk HPV16 positive and also over-expressed p16. A total of 14% (11/78) of the samples over-expressed p16.Conclusion: These findings present a mapping of HPV, EBV, HCMV and HAdV, including the HPV surrogate marker p16, in LSCC in this cohort. Except for EBV, which was detected in a third of the samples, data show viral infection to be uncommon, and that p16 does not appear to be a specific surrogate marker for high-risk HPV infection in LSCC.

Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment

Background Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC. Methods Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, $$\ge$$ ≥ 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response. Discussion A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC. Trial registration This trial is registered with ClinicalTrials.gov on October 1st, 2020 with Identifier: NCT04572100.

New Aspects and an Artificial Intelligence Approach for the Detection of Cervical Abnormalities

The COVID-19 pandemic has challenged health systems worldwide by decreasing their reserves and effectiveness. In this changing landscape, the urge for reallocation of financial and human resources represents a top priority. In screening, effectiveness and efficiency are most relevant. In the quest against cervical cancer, numerous molecular ancillary techniques detecting HPV DNA or mRNA or other related biomarkers complement morphological assessment by the Papanicolaou test. However, no technique is perfect as sensitivity increases at the cost of specificity. Various approaches try to resolve this issue by incorporating several examination results, such as artificial intelligence are proposed. In this study, 1,258 cases with a complete result dataset for cytology, HPV DNA, HPV mRNA, and p16 were used to evaluate the performance of a self-organizing map (SOM), an unsupervised artificial neural network. The results of the SOM application were encouraging since it is capable of producing maps discriminating the necessary tests and has improved performance.

Primary Bartholin Adenocarcinoma: a Rare Case and Radiotherapy as Definitive Treatment

Primary vulvar adenocarcinoma is a very rare neoplasm, accounting for only 1% of all gynecologic malignancies. Most of the glandular carcinomas originated from the Bartholin&rsquo;s gland. Because of the rare incidence, the pathogenesis and radiotherapy response are not fully understood. A 47-year-old female from our hospital was diagnosed with primary Bartholin adenocarcinoma and received radiotherapy as definitive treatment. We evaluated the presence of high-risk and low-risk human papillomavirus (HPV) DNA to associate the role of HPV infection, and evaluated its molecular features by the expression of vimentin, p16, estrogen receptor, progesterone receptor, S-100, and Ki 67.

Evaluation of Dynamic Thiol-Disulfide Homeostasis on Hpv Positive-Women in Progression to Cervical Intraepithelial Lesion

PURPOSE: Dynamic thiol disulfide homeostasis (TDH) is critical in cervical carcinogenesis at HPV infection as a sign of antioxidant consumption native and total thiol levels decrease in progress to cervical intraepithelial lesions. TDH is the main actor in signaling pathways, apoptosis, antioxidant and detoxification reactions. In this study, we aimed to evaluate the effect of TDH intraepithelial progression of cervical precancerous lesions on HPV positive women.METHODS: This was a prospective cross-sectional study. Subjects were selected from newly diagnosed high risk HPV DNA-positive patients. TDH results were calculated as the levels of disulfide, native and total thiol, the ratios of disulfide/total thiol (SS/SH+SS), disulfide/native thiol (SS/SH) and native thiol/total thiol (SH/SH+SS).RESULTS: A total of 146 women were included in the study. Study groups were as group one; control included 66 participants, group two; HPV DNA-positive women without preinvasive cervical lesion included 30 participants and group three; HPV DNA-positive women with preinvasive cervical lesion included 50 participants. Native and total thiol levels were elevated on HPV-positive women without preinvasive cervical lesions. There were no significant differences between groups related to the ratios of SS/SH, SS/ Total SH, SH/ Total SH levels. CONCLUSIONS: HPV infection related to oxidative stress has effects on oxidant/antioxidant balance and could be demonstrated in systemic circulation by TDH parameters. Consumption of thiol substances play role in the cervical neoplastic process, replacement with antioxidants would be a treatment option for HPV infections.