Comparison of multiplex PCR capillary electrophoresis assay and PCR-reverse dot blot assay for human papillomavirus DNA genotyping detection in cervical cancer tissue specimens.

Background: The study aimed to evaluate the positivity rates and genotype distribution of the multiplex PCR capillary electrophoresis (MPCE) and PCR-Reverse Dot Blot (PCR-RDB) assays for human papillomavirus (HPV) detection in cervical cancer tissue specimens, and to explore their detection principles and applications in large-scale population screening. Methods: The MPCE and PCR-RDB assays were performed separately on 425 diagnosed cervical cancer tissue specimens. Subsequently, the results of both assays were compared based on the HPV infection positivity rates and genotype distribution. Results: The overall positive rates of HPV genotypes for the MPCE and PCR-RDB assays were 97.9% and 92.9%, respectively. A p-value < 0.001 indicated a statistically significance difference in consistency between the two assays. The kappa value was 0.390, indicating that the consistency between both assays was fair. HPV16 was the most common single-genotype infection type, with infection rates detected via MPCE and PCR-RDB assays being 75.7% and 68.3%, respectively. In the age group >50 years, the HPV multiple-type infection rate detected via MPCE assay was significantly higher than that detected by the PCR-RDB assay, with a statistically significant difference (p = 0.002). Conclusion: To reduce the false-negative rate and improve screening efficiency, the MPCE assay, which targets the oncogenic gene E6/E7 segments, can be extended to the general female population for the early detection, diagnosis, and treatment of cervical cancer.

Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance.

OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.

Cost-effectiveness analysis of alternative screening strategies for the detection of cervical cancer among women in rural areas of Western Kenya.

While the incidence of cervical cancer has dropped in high-income countries due to organized cytology-based screening programs, it remains the leading cause of cancer death among women in Eastern Africa. Therefore, the World Health Organization (WHO) now urges providers to transition from widely prevalent but low-performance visual inspection with acetic acid (VIA) screening to primary human papillomavirus (HPV) DNA testing. Due to high HPV prevalence, effective triage tests are needed to identify those lesions likely to progress and so avoid over-treatment. To identify the optimal cost-effective strategy, we compared the VIA screen-and-treat approach to primary HPV DNA testing with p16/Ki67 dual-stain cytology or VIA as triage. We used a Markov model to calculate the budget impact of each strategy with incremental quality-adjusted life years and incremental cost-effectiveness ratios (ICER) as the main outcome. Deterministic cost-effectiveness analyses show that the screen-and-treat approach is highly cost-effective (ICER 2469 Int$), while screen, triage, and treat with dual staining is the most effective with favorable ICER than triage with VIA (ICER 9943 Int$ compared with 13,177 Int$). One-way sensitivity analyses show that the results are most sensitive to discounting, VIA performance, and test prices. In the probabilistic sensitivity analyses, the triage option using dual stain is the optimal choice above a willingness to pay threshold of 7115 Int$ being cost-effective as per WHO standards. The result of our analysis favors the use of dual staining over VIA as triage in HPV-positive women and portends future opportunities and necessary research to improve the coverage and acceptability of cervical cancer screening programs.

Comparison of HPV-positive triage strategies combining extended genotyping with cytology or p16/ki67 dual staining in the Italian NTCC2 study.

BACKGROUND: Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping. METHODS: Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance. FINDINGS: Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting. INTERPRETATION: Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years. FUNDING: Italian Ministry of Health (grant number RF-2009-1536040). Hologic-Genprobe, Roche Diagnostics, and Becton & Dickinson provided financial and non-financial support.

An Evaluation of High-Risk HPV in Squamous Cell Carcinomas of the Lip in a South African Cohort.

BACKGROUND: To determine the prevalence of HR-HPV in a series of lip SCC from South African patients, using currently accepted HPV-testing methodologies and to define the clinical and histomorphologic features of HPV-associated lip SCC. METHODS: Fifty SCC of lip and 50 control cases were tested for HR-HPV using p16 and HR-HPV DNA PCR. p16-equivocal/positive and HPV DNA PCR-positive SCC were further evaluated for the expression of HPV-16 and HPV-18 mRNA transcripts using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to confirm transcriptionally active HPV. RESULTS: p16 was positive in 22% (n = 11) and equivocal in 4% (n = 2) of the SCC. One p16-positive case showed positivity for both HPV-16 DNA and HPV-16 E6/E7 mRNA transcripts (HPV prevalence rate of 2%). The HPV-positive case was non-keratinizing and occurred in an 80-year-old female. The two p16-equivocal cases were HR-HPV DNA positive and mRNA PCR negative. p16 was found to have a positive predictive value of 9%. CONCLUSION: Findings from our cohort of lip SCC suggest that HR-HPV may have an insignificant role in the pathogenesis of SCC at this site. Due to its low ppv, p16 is insufficient to establish HR-HPV infection in SCC of the lip. The combination of p16 and DNA PCR appears to correlate with the presence of transcriptionally active virus. HPV E6/E7 mRNA detection is the gold standard for identifying HR-HPV. mRNA testing is not widely available in sub-Saharan Africa due to technical and financial constraints; however, the test appears to be of great value in p16-equivocal lip SCC.

Effectiveness of self-sampling human papillomavirus test on precancer detection and screening uptake in Japan: The ACCESS randomized controlled trial.

Japan is lagging in cervical cancer prevention. The effectiveness of a self-sampling human papillomavirus (HPV) test, a possible measure to overcome this situation, has not yet been evaluated. A randomized controlled trial was performed to evaluate the effectiveness of a self-sampling HPV test on detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and screening uptake. Women between 30 and 58 years old who did not participate in the cervical cancer screening program for ≥3 years were eligible and assigned to the intervention group (cytology or self-sampling HPV test) or control group (cytology). Participants assigned to the intervention group were sent a self-sampling kit according to their ordering (opt-in strategy). A total of 7337 and 7772 women were assigned to the intervention and control groups, respectively. Screening uptake in the intervention group was significantly higher than that in the control group (20.0% vs. 6.4%; risk ratio: 3.10; 95% confidence interval [CI]: 2.82, 3.42). The compliance rate with cytology triage for HPV-positive women was 46.8% (95% CI: 35.5%, 58.4%). CIN2+ was detected in five and four participants in the intervention and control groups, respectively; there was no difference for intention-to-screen analysis (risk ratio: 1.32; 95% CI: 0.36, 4.93). Self-sampling of HPV test increased screening uptake; however, no difference was observed in the detection of CIN2+, probably due to the low compliance rate for cytology triage in HPV-positive women. Efforts to increase cytology triage are essential to maximize precancer detections.

HPV DNA Integration at Actionable Cancer-Related Genes Loci in HPV-Associated Carcinomas.

In HPV-associated carcinomas, some examples of cancer-related genes altered by viral insertion and corresponding to potential therapeutic targets have been described, but no quantitative assessment of these events, including poorly recurrent targets, has been reported to date. To document these occurrences, we built and analyzed a database comprised of 1455 cases, including HPV genotypes and tumor localizations. Host DNA sequences targeted by viral integration were classified as "non-recurrent" (one single reported case; 838 loci), "weakly recurrent" (two reported cases; 82 loci), and highly recurrent (≥3 cases; 43 loci). Whereas the overall rate of cancer-related target genes was 3.3% in the Gencode database, this rate increased to 6.5% in "non-recurrent", 11.4% in "weakly recurrent", and 40.1% in "highly recurrent" genes targeted by integration (p = 4.9 × 10-4). This rate was also significantly higher in tumors associated with high-risk HPV16/18/45 than other genotypes. Among the genes targeted by HPV insertion, 30.2% corresponded to direct or indirect druggable targets, a rate rising to 50% in "highly recurrent" targets. Using data from the literature and the DepMap 23Q4 release database, we found that genes targeted by viral insertion could be new candidates potentially involved in HPV-associated oncogenesis. A more systematic characterization of HPV/host fusion DNA sequences in HPV-associated cancers should provide a better knowledge of HPV-driven carcinogenesis and favor the development of personalize patient treatments.

Clinico-pathological Factors in Malignant Transformation of RRP.

Various clinico-pathological factors play role in the papilloma proliferation and pathogenesis of Recurrent respiratory papillomatosis (RRP). However, it is not known if they are directly responsible for malignant transformation of these papillomas or not. We did this study to elucidate any such association. The most recent debrided tissue of RRP in 20 patients was evaluated for p16 expression, VEGF estimation (tissue expression and serum levels), and tissue HPV DNA concentration. The final histopathology results were then correlated with these pathological factors and with clinical factors like duration of illness, age of onset of symptoms, extent of disease, etc. Squamous papilloma was seen in 60%, dysplasia in 25%, and squamous cell carcinoma (SCC) in 15% of the patients. Positive immunostaining for p16 (staining in ≥70% of tumor cells) was seen only in one case, which was SCC. There was no statistically significant difference between p16 expression, tissue VEGF expression, serum VEGF levels, and tissue HPV DNA in any of the histological groups. The mean age of disease onset was significantly higher in patients with SCC (p = 0.03). A significantly higher number of patients with dysplasia had tracheobronchial involvement (p = 0.022). We concluded that no single pathological factor is solely responsible for development of malignancy in RRP, whereas clinical factors like tracheobronchial involvement and age of onset may contribute to development of dysplasia or carcinoma.

Validation of the VisionArray® Chip Assay for HPV DNA Testing in Histology Specimens of Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND: The detection of human papillomavirus (HPV) has several implications in the diagnostic work-up and management of oropharyngeal squamous cell carcinoma (OPSCC). The choice of HPV detection assay and testing algorithms differ across institutions and vary in cost, detection targets, technical feasibility, and turnaround time. In this study, we aimed to validate the VisionArray® HPV Chip for formalin-fixed and paraffin-embedded (FFPE) samples of OPSCC using the previously applied standard pan-HPV DNA PCR assay as a reference. METHODS: The validation cohort consisted of FFPE tissue samples from patients previously diagnosed with HPV DNA-positive OPSCC (n = 80), HPV DNA-negative OPSCC (n = 21), and a benign group of tumor samples consisting of Warthin's tumors (n = 20) and branchial cleft cysts of the lateral neck (n = 14). All samples were tested with p16 immunohistochemistry, pan-HPV DNA PCR, and the VisionArray® HPV Chip. RESULTS: The overall sensitivity and specificity of the VisionArray® HPV Chip assay were 100% [95% CI 95.5%; 100.0%] and 96.3% [95% CI 87.3%; 99.6%] and the positive predictive value and negative predictive value were 97.6% [95% CI 91.5%; 99.7%] and 100% [95% CI 93.2%; 100%], respectively. CONCLUSIONS: The VisionArray® HPV Chip assay can be recommended for high-risk HPV testing in FFPE tissue samples from OPSCC, providing both a fast and simultaneous genotyping for 41 clinically relevant HPV types.

Cervical cancer screening program in Indonesia: is it time for HPV-DNA tests? Results of a qualitative study exploring the stakeholders' perspectives.

OBJECTIVES: Cervical cancer is a significant public health concern in Indonesia, and effective screening methods are necessary to improve the detection and reduce mortality. This study aimed to explore the perspectives of high-level stakeholders involved in cervical cancer screening in Indonesia and whether the use of human papillomavirus-deoxyribonucleic acid (HPV-DNA) methods for cervical cancer screening is acceptable in Indonesian settings. METHODS: A qualitative research approach guided by realist evaluation was applied using focus group discussions (FGDs) between December 2021 and February 2022, conducted with stakeholders involved in cervical cancer screening in Indonesia. They were representatives of practitioners and policymakers involved in the screening, and were recruited through purposive recruitment. The data were analysed using inductive approach of thematic analysis. RESULTS: The analysis of two FGDs with 29 participants identified four main themes: (i) Visual inspection with acetic acid (VIA) method as the most common modality used for cervical cancer screening, (ii) the applied screening programs in the community, (iii) the perceived challenges on the screening program, such as limitations of the National Health Insurance benefits package and a lack of regulations regarding screening procedures, and (iv) the possibilities of HPV-DNA testing as another modality for cervical cancer screening. Incorporating HPV-DNA testing also needs to ensure the capacity of the workers and the readiness of healthcare facilities. CONCLUSION: Although HPV-DNA testing is a promising modality, challenges on the cervical cancer screening in Indonesia remain on the coverage, accessibility of the tools in practice and the women's awareness towards the screening. Ultimately, the findings of this study would help inform policies to improve cervical cancer screening programs in Indonesia.

Clinical Performance of Self-collected Specimen HPV-DNA vs Clinician- collected Specimen HPV-mRNA to Detect High-risk HPV and High-grade Cervical Lesions and Cancer.

OBJECTIVE: Self- collected specimens to detect high-risk (hr) HPV and high-grade cervical lesions (CIN2+) has been introduced aiming to increase cervical cancer screening coverage. The performance of self- collected specimen  compared to clinician collected specimen is one major concern. This study aimed to compare self-sampling HPV-DNA and clinician-sampling HPV-mRNA to detect hr-HPV and high-grade cervical lesions. METHODS: Women with abnormal cervical cytology and/ or positive hr-HPV who attended the colposcopy clinics in 10 tertiary hospitals in Bangkok were enrolled. Self-collected specimens were evaluated for  HPV DNA using Cobas® 4800 HPV test prior to the clinician-collected specimens which were tested for HPV mRNA with APTIMA® HPV Assay. Subsequent colposcopy with biopsy was performed. The detection rates of hr-HPV from both HPV tests and their performance to detect high-grade lesions pathology were compared. RESULTS: Data from 497 women's specimens were analyzed. Both samplings had 86.8% concordance rate in detecting hr-HPV (Kappa 0.670; 95% confidence interval [CI] 0.599-0.746, P value < 0.001). The sensitivity (95% CI) of self-collected specimen HPV DNA and clinician- collected specimen HPV-mRNA to detect high-grade lesions were 91.8% (85.4%-96.0%) and 90.2% (83.6%-94.9%) respectively. The corresponding negative predictive values (95% CI) were 91.9% (85.6%-96.0%) and 91.7% (86.0%-95.7%) respectively. CONCLUSION: HPV DNA testing from self-collected specimen to detect HR-HPV demonstrates high concordance with HPV mRNA testing from clinician-collected specimen. The sensitivity and negative predictive value of both tests to detect high-grade lesions are comparable.

Diagnostic value of HPV-DNA typing combined with serum NLR and DCLK1 for cervical cancer / 中国现代医生

@#Objective To investigate the value of receiver operating curve human papilloma virus(HPV)-DNA typing combined with serum neutrophil lymphocyte ratio(NLR)and bicorticoid kinase 1(DCLK1)levels in the early diagnosis of cervical cancer.Methods A total of 120 patients with early cervical cancer diagnosed in our obstetrics and gynecology department from August 2018 to June 2022 were randomly included as cervical cancer group,and 120 patients with benign lesions were included as benign group.The level of DCLK1 was detected by ELISA;NLR was detected by automatic blood cell analyzer;HPV subtypes in cervical secretions were detected by HPV genotyping gene chip detection system;the cut-off values of serum NLR and DCLK1 levels in the diagnosis of cervical cancer were analyzed by using the receiver operator curve(ROC);four table method was applied to analyze the diagnostic value of HPV-DNA typing,serum NLR,DCLK1 levels alone and in combination for cervical cancer.Results Compared with benign group,the levels of serum NLR and DCLK1 in cervical cancer group were obviously higher(P<0.05).The positive rate of HR-HPV in cervical cancer group was obviously higher than that in benign group(P<0.05).The ROC curve was drawn with serum NLR and DCLK1 levels as test variables,the results showed that the AUC of serum NLR and DCLK1 predicting early cervical cancer was 0.724 and 0.718,respectively,and the cut-off value was 3.08 and 3.32,respectively.HPV-DNA typing combined with serum NLR and DCLK1 detected 18 false positives and 17 false negatives,Kappa value was 0.725,which was consistent with pathological results.The sensitivity,negative predictive value and accuracy of HPV-DNA typing combined with serum NLR and DCLK1 levels in the diagnosis of early cervical cancer were obviously higher than those of HPV-DNA typing,serum NLR and DCLK1 levels alone(P<0.05).Conclusion The results of HPV-DNA typing combined with NLR and DCLK1 in the diagnosis of early cervical cancer are highly consistent with the pathological results,and the sensitivity and accuracy are obviously improved.

Value of HPV DNA,HPV E6/E7 protein and TCT in cervical intraepithelial neoplasia and cervical cancer screening / 中国现代医生

@#Objective To investigate the value of human papilloma virus(HPV)DNA,HPV E6/E7 protein and thin-prep cytology test(TCT)in cervical intraepithelial neoplasia(CIN)and cervical cancer screening.Methods A total of 190 adult women who received early cervical cancer screening in Department of Gynecology,Zhuji People's Hospital from July 2021 to June 2022 were selected as the study objects.HPV DNA,HPV E6/E7 protein and TCT were detected,respectively,and further colposcopic biopsy was performed.The diagnostic efficacy of HPV DNA,HPV E6/E7 protein and TCT in patients with different lesions were compared.Results The positive rates of HPV DNA,HPV E6/E7 protein,TCT and combined detection in CIN3 and cervical cancer patients were significantly higher than those in cervicitis patients(P<0.05).The positive rates of HPV DNA,HPV E6/E7 protein,TCT and combined detection in cervical cancer patients were significantly higher than those in CIN1 patients(P<0.05).The positive rates of HPV DNA,HPV E6/E7 protein,TCT and combined detection in CIN2+ patients were significantly higher than those in CIN1-patients.The sensitivity,specificity,positive predictive value and negative predictive value of HPV DNA,HPV E6/E7 protein and TCT in the diagnosis of high-grade lesions were 90.80%,30.10%,52.32%and 79.48%,respectively.Conclusion HPV DNA,HPV E6/E7 protein and TCT can be used as screening methods for cervical cancer and precancerous lesions,with the combination of the three being the most sensitive.

Male Human Papillomavirus Infection and Genotyping in Turkey.

BACKGROUND: High-risk (HR) Human Papillomavirus (HPV) has been shown to play an important role in men in various locations in Turkey. This study aims to screen the male persistent infection with the high-risk human papillomavirus (HPV) genotype status in Turkey to provide a reference basis for formulating prevention strategies for the development of genitourinary tract neoplasia. METHODS: The HPV QUANT-21 Quantitative RT-PCR Kit® was used to identify and quantify low-risk HPV (HPV 6, 11, 44) and high-risk (HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) from male individuals in Turkey. RESULTS: Of the total 1304 samples, 473 were positive for at least one HPV genotype, with an overall frequency of 36.2%. Two-hundred fifty-four patients were positive only for one or more LR   HPV genotypes (54%), and 219 patients were positive for one or more HR HPV genotypes (46%). The LR HPV genotype frequency was 53.7%, while the HR HPV genotype frequency was 46.3%. Our technology had the positive advantage of being able to calculate concentrations for each genotype. Genotype 51 was second in frequency but had the highest average concentration of 5.38 log (copies/sample). CONCLUSION: The presence and genotype of the virus before HPV vaccination are also of increasing importance. The data obtained will serve as a guide for prevention strategies, especially vaccination. Based on our findings there is a need of new estimates of the efficacy of currently available HPV vaccines and to develop a screening program to prevent and reduce the incidence of genitourinary tract neoplasias in Turkey. Further studies are planned to measure and define the high levels of infection that may lead to the development of cervical tumors. Using this technique, it may be possible to make clinical decisions about the extent of cytological alterations.

Relevance of Partial p16 Immunostaining in Oral Squamous Cell Carcinoma and Co- Relation with HPV DNA Status.

INTRODUCTION: Immunostaining criteria for p16 positivity in oropharyngeal squamous cell carcinoma have been laid down by College of American Pathologists (CAP) and the American Society of Clinical Oncology (ASCO). The staining should be of moderate to strong intensity seen in 70 percent of the tumor cells. Recent studies have pointed out that a small minority of cases are missed using p16 as the surrogate marker at above mentioned cut off. By convention the same criteria have been used for oral squamous cell carcinoma. MATERIAL AND METHODS: The authors revisited the results of their previous study where immunohistochemistry for p16 was found to be positive by AJCC criteria in 139 out of 800 cases of oral squamous cell carcinoma. For this study, all the p16 immunonegative cases (by AJCC criteria) were analysed again for partial staining patterns, defined for this study as cases with 50-75% cells showing 2+/3+ intensity of nuclear p16 immunostaining and for basal predominant pattern of immunostaining. These cases were subjected to HPV DNA PCR. RESULTS: Out of the 661/800 cases found to be negative for p16 immunohistochemistry, a total of 34/800(4.25%) showed partial staining based on the criterion of 50-75% cells showing p16 immunostaining intensity of 2/3+.The basal predominant pattern of immunostaining for p16 was seen in 43/800 (5.38%) cases. When these cases were subjected to HPV DNA analysis, 11/34 (32.35%) of the cases showing partial staining and 02/43 (4.7%) of the cases showing basal predominant pattern of p16 immunostaining were found to be HPV-DNA positive. CONCLUSION: The inclusion of partial immunostaining patterns of p16 in HPV analysis of oral squamous cell carcinoma can improve our understanding of HPV driven oral squamous cell carcinoma.

Screening for Cervical Cancer in Pregnancy.

Cervical cancer remains a leading cause of cancer related morbidity and mortality in low/low-middle income countries. Lack of screening is the leading cause of cases being diagnosed in advanced stages and screening is still opportunistic in a majority of these countries. Hospital visits during pregnancy provides a window of opportunity to screen these susceptible women and reduce the burden of disease. Screening women during pregnancy is not practiced widely due to concerns of pregnancy loss, bleeding and a lack of clear information among patients as well as healthcare professionals.

Cervical Intraepithelial Neoplasia Grade 3 in the Third Trimester of Pregnancy: A Case Report.

The incidence of malignancies during pregnancy has been on the rise in the recent years, primarily due to an increase in older age pregnancies. This poses a significant risk to both the mother and the developing fetus. We present the case of a 29-year-old woman who experienced intermittent vaginal bleeding during her pregnancy. In the last trimester, the patient presented with abnormal vaginal bleeding and abdominal pain. The gestational age was 37.6 weeks. Notably, to our knowledge, there have been no reported cases of grade 3 cervical intraepithelial neoplasia in the third trimester.

HPV genotype-specific distribution and attributable risk in cervical intraepithelial neoplasia in a referral population with a history of LSIL.

BACKGROUND AND OBJECTIVE: CINtec PLUS and cobas HPV tests (Roche) were previously ascertained for triaging an LSIL referral population [1]. As part of this study, genotype-specific distribution and attributable risk of high-risk (HR)-HPV in cervical intraepithelial neoplasia (CIN) were determined. METHODS: Archived cervical specimens in ThinPrep PreservCyt (Hologic Inc) from the LSIL referral population (n= 533) were genotyped using the Anyplex II HPV HR test (Anyplex, Seegene Inc). Since the study specimens had been in storage in ambient temperature for 31-47 months since collection, Anyplex results were compared with that of the initial cobas testing of fresh specimens to validate the suitability and stability of specimens for the present study. RESULTS: Overall, Anyplex test was positive in 63% (336/533) vs. 55.7% (297/533) for cobas test. Anyplex test performed identical to cobas test identifying 93.2% (82/88) of ⩾CIN2/adenocarcinoma in situ (AIS). Anyplex test detected genotypes 16/18 in 15.7% (36/230) ⩽CIN1 vs. 45.5% (40/88) ⩾CIN2/AIS; the corresponding figures were 13.5% (31/230) and 45.5% (40/48) for the cobas test. Genotype 16 showed increasing attribution, 13.2% in CIN1, 27.1% in CIN2 and 40% in CIN3/AIS. Of the 12 other high-risk (OHR) types collectively identified by cobas, Anyplex test specifically detected, in decreasing order, genotypes 51, 31, 35, 56, 39, and 45 as the most frequent types, often in multiple-type infections, in 64.8% ⩾CIN2. Regardless, estimated attribution was evident for each of the 12 OHR types in ⩾CIN2. Multiple-type infections were more frequent than single-type infections in all CIN grades. CONCLUSIONS: Attributable risk of all HR-HPV genotypes targeted by both Anyplex and cobas tests was evident in ⩾CIN2/AIS Testing for these genotypes in HPV primary cervical screening and cytology triage could identify those at increased risk of cervical cancer and also be beneficial in the management of LSIL referral populations.

Rates of Primary and Secondary Prevention of Cervical Cancer: A Study in a Province in the South of Italy.

In Italy, cervical cancer represents the fifth most prevalent cancer in women under 50 years of age and is one of the most commonly detected lesions globally. Given the developing burden of the disease and the availability of both primary and secondary prevention measures, their accurate surveillance is of paramount importance. The aim of this study was to evaluate the trends in cervical cancer screening adherence in the period between 2020 and 2022, as well as to evaluate positive tests, identifying the most frequently associated genotypes and the vaccination coverage. The study sample was made up of 6880 women from the health district of Messina. We highlighted that there was a high proportion of positive results in the investigated period, with a high prevalence of HSIL. Moreover, HPV vaccination coverage was clearly inadequate, as was adherence to screening, both far away from WHO goals. This finding is probably linked to inadequate communication and awareness of the issue in the population and to the lack of data relating to tests carried out privately. In accordance with existing data in the literature, the introduction of the HPV-DNA test in Sicily made it possible to identify women positive for the genotypes most frequently involved in the etiopathogenesis of neoplastic lesions (genotypes 16 and 18), as well as for those in the "others" category, which should be investigated because some of them could have an impact on carcinogenicity and, for this reason, a future vaccine including them could represent a new prevention weapon.

Circulating cell-free HPV DNA is a strong marker for disease severity in cervical cancer.

For cervical cancer (CC), circulating cell-free HPV DNA (ccfHPV) may establish disease severity. Furthermore, HPV integration has been correlated to viral load and survival. In this study, pre-treatment plasma from 139 CC cases (50 primary surgery patients, 22 primary surgery + adjuvant oncological therapy patients, and 67 primary oncological therapy patients) was collected (2018-2020). Furthermore, plasma from 25 cervical intraepithelial neoplasia grade 3 patients and 15 healthy women (negative controls) were collected. Two next-generation sequencing (NGS) panels were used to establish ccfHPV presence and human papillomavirus type 16 (HPV16) integration status. ccfHPV was detected in four primary surgery (8.0%), eight primary surgery + adjuvant oncology (36.4%), and 54 primary oncology (80.6%) patients. For primary oncology patients with HPV16-related cancer (n = 37), more ccfHPVneg than ccfHPVpos patients had HPV16 integration (P = 0.04), and in patients with HPV16 integration (n = 13), ccfHPVpos patients had higher disease stages than ccfHPVneg patients (P = 0.05). In summary, ccfHPV presence is related to disease severity and may add to the debated Sedlis criteria used for identifying patients for adjuvant oncological therapy. However, ccfHPV detection is influenced by HPV integration status and disease stage, and these factors need to be considered in ccfHPVneg patients.