HPV Positivity Research Articles

Impact of knowledge of HPV positivity on cervical cytology performance in latin america.

Cervical cytology is recommended by WHO as a triage option in HPV-based cervical cancer screening programmes. We assessed the performance of cytology to detect CIN3+ without and with knowledge of HPV positivity. Women were screened with cytology and HPV across ESTAMPA study centres in Latin America. Screen-positives were referred to colposcopy with biopsy and treatment as needed. Cytology was initially interpreted without knowing HPV results. A subset of cytologies from HPV-positive women were re-interpreted at the same laboratories, with knowledge of HPV status, blinded to previous cytology and histological diagnosis. Performance indicators for cytology to detect CIN3+ without and with knowledge of HPV positivity were estimated. A total of 4,087 women were included, of which 490 had histologically confirmed CIN3 + (455 CIN3 and 35 cancers). Cytology sensitivity without knowledge of HPV positivity for CIN3+ was 47.2% (95% CI: 42.5-51.9), whereas with knowledge of HPV positivity, the sensitivity was higher (58.9%, 95% CI: 54.2-63.5), p < .0001. The specificity without knowledge of HPV was 89.4% (95% CI: 88.2-90.5), while with knowledge of HPV positivity was 78.9% (95% CI: 77.4-80.4), p < .0001. Performance estimates varied by study centre for cytology without knowing the HPV positivity, (range from 32.8% to 61.5% for sensitivity; range 80.7% to 98.6% for specificity). Similarly, performance varied with knowledge of HPV positivity (36.1% to 93.4% for sensitivity; 39.6% to 98.6% for specificity). The increase in sensitivity of cytology with HPV knowledge was limited and highly variable, reinforcing the need for alternative triage methods to support cervical cancer elimination goals.

Prediction of high-grade cervical precancerous abnormalities: The role of personal factors, vaginal microflora, sexually transmitted infections, and high-risk human papillomavirus.

High-risk human papillomavirus infection (HR-HPV) is necessary but not the only factor needed to develop cervical cancer. It is essential to estimate cervical cancer development risk in the population of high-risk HPV-positive women and to avoid unnecessary examinations and treatment in low-risk individuals. The study aimed to identify associations between different personal factors, vaginal microflora, sexually transmitted, high-risk HPV infection, and various degrees of cervical precancerous lesions. A study was performed in 2016-2020. The study group consisted of 112 patients with abnormal cervical cytology results referred for colposcopic examination. 120 women who came for a routine gynecological check-up were included in the control group. Material from the cervix and upper vaginal fornix was taken for pH measurement, wet mount microscopy, testing the six most common high-risk HPV DNA types (16/18, 31, 33, 45, 58), HPV E6/E7 mRNA, and 7 genital infections-C. trachomatis, N. gonorrhea, T. vaginalis, M. hominis, M. genitalium, U. urealyticum, U. parvum. Results showed that women with all grades of cervical intraepithelial neoplasia (CIN) more often were smokers, had increased vaginal pH levels, and had positive HR-HPV DNA and HR HPV E6/E7 mRNA expression. Abnormal vaginal microflora, especially types associated with aerobic vaginitis, and M. hominis were significantly more often found in women with CIN2+. The presence of C.trachomatis, U. parvum, and U.urealyticum did not differ between the groups. The most important factors independently associated with CIN2+ were positive high-risk HPV E6/E7 mRNA expression (OR 59.4, 95% CI 14.84-237.51), and positive high-risk HPV DNA (OR 3.9, 95% CI 1.16-13.23). Higher education level was associated with reduced risk of CIN2+ (OR 0.2, 95% CI 0.07-0.71). In conclusion, this study reports HR-HPV DNA of the most common six types and E6/E7 mRNA positivity as the most significant factors associated with CIN2+ lesions and higher education related to lower risk of high-grade cervical lesions.

Challenges and Considerations in Diagnosing and Managing p16+-Related Oropharyngeal Squamous Cell Carcinoma (OPSCC) with Neck Metastasis: Implications of p16 Positivity, Tobacco Exposure, and De-Escalation Strategies

Background: The incidence of patients showing neck metastasis and no obvious primary tumor at the initial diagnostic evaluation or neck cancer of unknown primary (NCUP) is rising. It is estimated that a relevant part of these tumors arises in the tonsillar crypts or base of the tongue and are p16+-related. However, today, the detection rate of the primary tumor is suboptimal. Identifying the primary tumor and its biomolecular characterization is essential since it influences the treatment administered, possibly reducing radiation fields and providing de-escalation to primary surgical management. However, p16 IHC (immunohistochemistry) might not be sufficient to diagnose HPV-related OPSCC. The other subset of patients discussed are the HPV-positive patients who have a history of tobacco exposure and/or p53 mutations. Possible factors that could negatively influence the outcomes of these patients are investigated and discussed below. So, this paper aims to analyze the diagnostic, bio-molecular, clinico-radiological, morphological, prognostic and therapeutical aspects of p16-positive OPSCC, highlighting the possible bias that can occur during the diagnostic and prognostic process. Methods: A narrative review was conducted to investigate the biases in the diagnostic and therapeutic process of two groups of patients: those who are p16-positive but HPV-negative patients, and those who are p16-positive and HPV-positive with exposure to traditional risk factors and/or p53 mutations. The keywords used for the literature research included the following: NCUP, OPSCC, p16IHC, HPV testing, p16 positive HPV negative OPSCC, p16 positive HPV positive OPSCC, tonsillectomy, tobacco exposure, p53 mutations, cystic neck metastasis, extranodal extension (ENE), radiotherapy, de-escalation and neck neck dissection. Results: HPV-positive OPSCC has specific clinico-radiological features. Bilateral tonsillectomy should be considered for the identification of the primary tumor. P16 IHC alone is not sufficient for diagnosing HPV-related OPSCC; additional detection methods are required. The role of tobacco exposure and p53 mutations should be investigated especially in cases of HPV-positive tumors. Extranodal extension (ENE) must be taken into consideration in the prognostic staging of HPV-positive tumors. Surgical primary treatment involving neck dissection (ND) and bilateral tonsillectomy followed by adjuvant radiation may represent the most appropriate approach for N3 cases. Diagnosis, prognosis and therapeutical implications must be addressed considering clinical, biomolecular and morphological aspects. At least today, the numerous biases that are still present influencing the diagnostic and prognostic process do not permit considering de-escalation protocols. Conclusions: A precise and accurate diagnosis is required in order to adequately stage and manage p16+ OPSCC, particularly with neck metastasis. The role of tobacco exposure and/or p53 mutations must be considered not only in p16+ OPSCC but especially in HPV-positive OPSCC. Until a more accurate diagnosis is possible, ENE should be considered even in p16+HPV+ OPSCC. Primary surgery with unilateral ND and bilateral tonsillectomy might be the treatment of choice given the numerous diagnostic and prognostic pitfalls. Therefore, it is inappropriate and risky to propose de-escalation protocols in routine clinical practice due to the risk of undertreatment.

Epidemiological and Typing Features of HPV Co-Infections in MSM with Mpox: A Hospital-Based Prospective Study

ObjectivesRecent mpox outbreaks highlight diverse transmission modes, with sexual behavior prominent in China's IIb strain. Nevertheless, despite HPV being a common sexually transmitted pathogen, there is a paucity of research into its coexistence and genotype distribution within this patients population. MethodsWe conducted a study at the Third People's Hospital of Shenzhen from May to September 2023. We collected information on mpox patients, including their sociodemographic and clinical characteristics. Anal swabs were collected for HPV genotyping. ResultsAmong 73 MSM mpox cases, HIV positivity was 56.2% (41/73) and HPV positivity 80.4% (41/51). Multiple HPV infections were prevalent (56.9%, 29/51), especially among HIV-positive (93%, 27/29). HPV16 (29.3%, 12/41) was the most common high-risk genotype, followed by HPV59 (26.8%, 10/41), HPV42 (19.5%, 8/41), HPV6 (14.6%, 6/41), and HPV54 (14.6%, 6/41). HPV infection was significantly associated with HIV infection (p=0.001). Additionally, HIV infection (p=0.001) and PCR-detected positive sites for mpox (p=0.047) were associated with high-risk HPV infection. ConclusionsIn this study, most of the mpox patients were found to be infected with HPV, mostly with high-risk types and multiple infections. Therefore, it is strongly recommended that mpox-infected individuals intensify HPV-related screening, prevention, and treatment measures.

Comparative study of triage strategies for women with atypical squamous cells of undetermined significance in the post-vaccine era.

The research focused on a comparative analysis of triage strategies for women with Atypical Squamous Cells of Undetermined Significance (ASC-US) before and after receiving the HPV vaccine, aiming to optimize cervical cancer prevention strategies, especially in resource-limited healthcare settings. Between September 2018 and December 2023, 7,511 women aged 21 years or older who underwent liquid-based cytology for cervical cancer screening were recruited. Women diagnosed with ASC-US were included in the study. All participants underwent HPV testing and liquid-based cytology examination, and those with abnormal results were referred for colposcopy. Women with abnormal colposcopy findings underwent further histopathological examination. The gold standard for diagnosis was pathological, with cervical intraepithelial neoplasia grade 2 or higher (CIN2+) on histology as the endpoints. In the final analysis, 933 women with ASC-US were enrolled as the unvaccinated group, with 179 of them testing positive for HPV 16/18. Assuming that all women would receive the bivalent vaccine targeting HPV 16/18 in the post-vaccine era, and given that the vaccine protection rate is 100% against HPV 16/18, then 754 women excluding those of HPV 16/18 positive would comprise the vaccinated group. In the unvaccinated group, the overall HPV positivity rate was 59.27% among ASC-US women, with a 100% HPV prevalence rate among those with CIN2+ lesions. The combination genotyping model of HPV16/18 showed the highest specificity (81.77%) and the lowest referral rate (32.37%). In the vaccinated group, the HPV positivity rate was 49.61% among ASC-US women, with a 100% HPV prevalence rate among those with CIN2+ lesions. The specificity of HPV33/58 was the highest (86.99%), and the colposcopy referral rate was lowest (27.54%), with statistical significance. Sensitivity, positive predictive value, and negative predictive value were not statistically significant. HPV16/18 demonstrated a more efficacious triaging effect in the unvaccinated group. HPV33/58 will potentially replace HPV16/18 as the priority screening genotyping among vaccinated populations.

Histomorphology based prediction of p16 immunopositivity and p16/HPV DNA co-positivity in oral squamous cell carcinoma

The histomorphological features predictive of p16 and human papilloma virus (HPV DNA) positivity in oropharyngeal carcinoma have been a matter of much debate. However, only few studies have been done on oral squamous cell carcinoma (OSCC) to correlate the histomorphological features with p16 and HPV DNA positivity. Oral squamous cell carcinoma has distinct etiopathogenesis, treatment and prognosis as compared to oropharyngeal carcinomas.A total of 800 oral squamous cell carcinoma biopsy cases were evaluated for features suggestive of HPV infection like basaloid appearance, absence of stromal reaction, nests and lobules of tumor cells with pushing borders, central necrosis, lympho-epithelial morphology, koilocytes, and non-keratinizing or hybrid morphology. Immunohistochemistry was performed for p16 expression (E6H4 clone, CINtec histology, Roche diagnostics). The cases which showed 2+/3+ (from moderate to high intensity) staining with >75 % cells were considered as p16 immunopositive. All the p16 immunopositive cases were subjected to real-time PCR (polymerase chain reaction) for HPV DNA detection to confirm HPV positivity. A total of 139 (17.37 %) OSCC cases were p16 immunopositive and out of these 104 (104/139, 74.8 %) cases showed HPV-DNA PCR positivity. None of the features were found to be predictive on multivariate logistic regression analysis. However, on bivariable analysis, nest/lobule with pushing border was the only histopathological feature which had a significant correlation with p16 immunopositivity (P value = 0.0001) and p16 and HPV DNA copositivity (P value = 0.0001). (Fisher's exact test -two tailed).To conclude-morphology is not really predictive of HPV positivity in OSCC cases. Only one feature- nests and lobule with pushing border is suggestive on bivariable analysis.

Abstract C017: Race-Specific Patterns of Vaginal Microbiome and HPV Infections Predict Risk of Precancerous Cervical Lesions

Abstract Background: Our previous research indicated that high-grade squamous intraepithelial lesions (HSIL), precursors to cervical cancer (CCa), are influenced by the vaginal microbiome (VMB) differentially by self-reported race. VMB enriched for certain anti-inflammatory Lactobacillus species confer protection against the risk of HSIL for white, but not Black women. Black women exhibit greater VMB diversity (associated with HPV tumorigenesis) and a lower prevalence of anti-inflammatory Lactobacillus species. But not all Black women with diverse VMB develop HSIL. Objective: Given HPV's essential role in cervical cancer, we aimed to assess the influence of sociodemographic, clinical, and microecological HPV attributes on HSIL risk within the context of the vaginal microbiome's variation by race. Methods: The VMB and HPV profiles of 1,168 women were analyzed alongside over 100 sociodemographic and clinical variables. Spearman’s correlation, Point-Biserial Correlation, chi-squared tests, and machine learning models, were employed to evaluate associations between sociodemographic, clinical, and microecological variables with HSIL, with a particular focus on the impact of race on these relationships. Results: The cohort was predominantly Black (72%), showing no significant race-based differences in HPV positivity (45%). However, HSIL incidence was nearly twice as high in Black (7%) compared to White women (4%). Women with HSIL had a higher prevalence of non-Lactobacillus-dominant VMB (68% vs. 51%) and were more likely to be HPV+ (73% vs. 44%) than those without HSIL. Co-infection with multiple HPV strains was associated with a higher risk of CIN3. Specifically, HPV16, HPV56, HPV58, HPV33, and HPV42 infections were significantly associated with higher CIN3 risks. The random forest model identified the relative abundance of Lactobacillus crispatus as the most essential factor in predicting CIN3 risk, followed by the number of HPV strains per sample. However, differential abundance analysis specifically indicated lower L. crispatus levels were associated with HSIL in white but not Black women. Conversely, HPV abundance was only associated with HSIL in Black women. Additionally, Black patients with 2 or more HPV co-infections had a higher likelihood of being diagnosed with CIN3+ compared to white counterparts. ML models highlighted different HPV-specific HSIL predictors by race: HPV number, and HPV 56, 16, and 33 in Blacks; sexual partners, HPV 90, 56, and 16 in whites. Conclusions: Our findings reveal race-specific interplays among individual risk factors, HPV infection, and VMB composition in HSIL development. The identification of key microbial and viral predictors highlights the importance of personalized approaches in preventing and managing HSIL, particularly among racially diverse populations. Citation Format: Katherine Y. Tossas, Bin Zhu, Katarzyna Tyc, Myrna Serrano, Jerome Strauss, Gregory Buck. Race-Specific Patterns of Vaginal Microbiome and HPV Infections Predict Risk of Precancerous Cervical Lesions [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C017.

Oral Mucosal Human Papillomavirus and Epstein-Bar Virus Rates in Patients with Dry Mouth and/or Sjögren's Syndrome in a Hungarian Cohort.

To find an association between oral mucosal human papilloma- and/or Epstein-Barr (HPV, EBV) virus infection in patients with dry mouth and/or Sjögren's syndrome (SS) compared to healthy controls and to find connections with salivary gland histopathological alterations. Ninety-two participants were divided into four groups: 1. healthy controls (n &#61; 32); 2. xerostomia (n &#61; 28); 3. hyposalivation (n &#61; 22); and 4. SS groups (n &#61; 10). To detect virus infection brush biopsy was outlined in all groups. Detections of virus-specific sequences were achieved with polymerase chain reaction (PCR). Lip biopsy and histopathological assessment was performed in groups 2, 3 and 4. HPV positivity of oral mucosal cells was shown in group 1: 1 (3.12%); group 2: 3 (10.7%); group 3: 2 (8.26%); and in group 4: 0 of the samples. EBV was present in group 1: 14 (43.7%); group 2: 17 (60.7%); group 3: 6 (27.3%); and in group 4: 5 (50%) of the cases. There was no statistically significant difference between the attributes. Intact salivary gland in 28.2%, chronic sialadenitis in 28.2%, stromal fibrosis in 6.5%, lipomatous atrophy in 8.6%, fibrous atrophy in 6.5% and positive focus score (SS) in 26.1% were found in the subjects. Neither HPV nor EBV infection caused statistically significantly more histological abnormalities. Orofacial mucosal HPV and/or EBV DNA rates did not differ statistically significantly in patients with xerostomia or hyposalivation or SS compared to healthy controls, therefore, it cannot prove the provocative role of these viruses in dry mouth and/or SS. Neither dry mouth nor SS were accompanied by statistically significantly more salivary gland alterations in HPV- and/or EBV-positive subjects; these alterations are frequent in the virus-negative cases too.

Expression and prognosis of DSG-2, CXADR, CD46 in head and neck squamous cell carcinoma

ObjectivesInvestigating the expression and prognostic significance of adenovirus receptors DSG-2, CXADR and CD46 in head and neck cancer. Methods104 patients with HNSCC (77 OPSCC, 27 LSCC) were retrospectively included in the study. Immunohistochemical staining was performed on all selected slides to detect the expression of DSG-2, CXADR, CD46 and the immunoreactive score (IRS) was determined from the number of positively stained tumor cells and their staining intensity. Furthermore, the respective HPV status was determined by immunohistochemical staining against p16 and HPV-PCR. Results81.7 % of the tumors showed DSG-2, 34.6 % of the tumors showed CXADR and 57.7 % of the tumors showed CD46 expression. A high DSG-2 IRS correlated significantly with an advanced tumor size (p= 0.003), increased grading (p=0.012) and positive HPV status (p=0.024) in OPSCC. A high CXADR IRS was significantly associated with a positive lymph node status (p= 0.041) in LSCC and an advanced AJCC stage (p= 0.012) and a positive HPV status (p= 0.009) in OPSCC. No significant correlation could be shown regarding CD46 expression and clinical tumor data. There was no effect of DSG-2, CXADR, and CD46 expression on 5-year overall and on 5-year disease-free survival. ConclusionNo prognostic significance of the expression of DSG-2, CXADR or CD46 in HNSCC was seen. DSG-2, CXADR and CD46 are expressed in HNSCC, so that optimization of oncotherapy with adenoviral vectors appears promising. Due to the significantly increased expression of DSG-2 and CXADR in advanced OPSCC tumors, there is potential for optimizing oncotherapy here in particular.

Anal high-grade intraepithelial neoplasia and cancer in women living with HIV and HIV-negative women with other risk factors.

To determine the prevalence and the risk factors for anal high-grade intraepithelial neoplasia and anal cancer (HSIL+) in women living with HIV (WLWHIV), and to compare them to HIV-negative women with other risk factors. Prospective cohort study. WLWHIV and HIV-negative women with other risk factors were included. Screening for anal HSIL+ using anal cytology and HPV testing was performed. A high-resolution anoscopy with directed biopsy was also performed in patients with an abnormal cytology result or a positive HPV testing for high-risk (HR) genotypes, and in those with anal symptoms. The period prevalence of anal HR-HPV infection and histological HSIL was 57.9% and 10.9% among WLWHIV, and 60.8% and 9.2% among HIV-negative women. The prevalence of anal HPV 18 infection was higher in WLWHIV. The risk factors for anal HSIL+ in WLWHIV included anal HPV 16, other HR genotypes and low-risk genotypes infection, as well as a history of vulvar HSIL+. In HIV-negative women, the risk factors included anal HPV 16 infection, history of anogenital warts and of vulvar HSIL+, and immunosuppressive treatment. A high prevalence of anal HPV infection and HSIL was observed in WLWHIV and women with other risk factors. Both groups share anal HPV 16 infection and history of vulvar HSIL+ as risk factors for the development of anal HSIL+. Genotyping for anal HPV 16 may help identify women at higher risk of anal cancer.

HPV integration: a precise biomarker for detection of residual/recurrent disease after treatment of CIN2-3

BackgroundThis study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3.MethodsA total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated.ResultsAmong the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence.ConclusionsThe HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3.

Challenges associated with follow-up care after implementation of an HPV screen-and-treat program with ablative therapy for cervical cancer prevention

BackgroundCervical cancer is a preventable cancer; however, decreasing its prevalence requires early detection and treatment strategies that reduce rates of loss to follow-up. This study explores factors associated with loss to follow-up among HPV-positive women after implementation of a new HPV-based screen-and-treat approach for cervical cancer prevention in Iquitos, Peru.MethodsWe conducted semi-structured interviews with “obstetras” (i.e., midwives) (n = 15) working in cervical cancer prevention and women (n = 24) who were recorded as lost to follow-up after positive HPV results. We used the Health Care Access Barriers Model to guide analyses. We utilized manifest content analysis to describe barriers to follow-up according to the obstetras and thematic analysis to report themes from the women’s perspectives. We also report the steps and time taken to contact women.ResultsWe found an incomplete and fragmented patient monitoring system. This incomplete system, in conjunction with challenges in contacting some of the women, led to structural barriers for the obstetras when attempting to deliver positive results. Women in this study expressed a desire to receive treatment, however, faced cognitive barriers including a lack of understanding about HPV results and treatment procedures, fear or anxiety about HPV or treatment, and confusion about the follow-up process. Women also reported having important work matters as a barrier and reported frequently using natural medicine. Reported financial barriers were minimal.ConclusionThis study highlights the barriers to follow-up after implementation of a primary-level HPV-based screen-and-treat approach. While some barriers that have previously been associated with loss to follow-up were not as prominently observed in this study (e.g., financial), we emphasize the need for screen-and-treat programs to focus on strategies that can address incomplete registry systems, structural challenges in results delivery, cognitive barriers in understanding results and treatment, and work-related barriers.

HPV Self-Sampling for Cervical Cancer Screening in Under-Screened Saskatchewan Populations: A Pilot Study.

Of all cancers in female Canadians, the most rapidly increasing incidence is that of cervical cancer. The objective of this pilot study was to assess how HPV self-sampling might improve cervical cancer screening participation in both urban and rural settings in Saskatchewan, one of the most sparsely populated provinces in Canada. Study groups consisted of n = 250 participants to whom self-swabbing kits were mailed with instructions and n = 250 participants to whom kits were handed out in 6 urban and rural clinics. The inclusion criteria selected subjects aged 30-69 years who were Saskatchewan residents for at least 5 years with valid health coverage, had a cervix, and had no record of cervical cancer screening in 4 years. The returned samples were analyzed for specific HPV strains using the Roche Molecular Diagnostics Cobas 4800® System. The overall response rate was ~16%, with the response to the handout distribution being roughly double that of the mailout. While HPV positivity did not differ across the distribution groups, participants at a specific inner-city clinic reported significantly higher positivity to at least one HPV strain as compared to any other clinic and all mailouts combined. For this high-risk population, in-person handout of self-sampling kits may be the most effective means of improving screening.

Immediate risk of cervical intraepithelial neoplasia and diagnostic value of colposcopy among cytology-negative women with oncogenic HPV: a retrospective study

BackgroundCervical cancer screening results that are negative for cytology but positive for high-risk human papillomavirus (HR-HPV) are not uncommon. One-year follow-up is suggested for patients with no history of HPV positivity under the most recent American Society of Colposcopy and Cervical Pathology (ASCCP) guidelines (2019). The aim of this study was to evaluate the immediate risk of cervical intraepithelial neoplasia (CIN) among cytology-negative patients positive for HR-HPV. The diagnostic accuracy of colposcopy in these patients was investigated.MethodsA retrospective study was conducted in patients who were cytology negative but HR-HPV positive and referred for colposcopy from January 2022 to August 2023. Patients were compared in terms of the immediate rate of CIN lesions among the HPV16-positive group, the HPV18-positive group and the non-16/18 HR-HPV-positive group. The distribution of CIN2 + lesions according to age was evaluated. The factors associated with the accuracy of colposcopy were evaluated using univariate and multivariate logistic regression.ResultsAmong the 372 patients, 195 had chronic cervicitis, 131 had CIN1, 37 had CIN2/3, and nine had carcinoma. The immediate rates of CIN2 + lesions and CIN3 + lesions in patients who were not HR-HPV16/18-positive were comparable to those in patients who were HPV16/18-positive (P = 0.699). In addition, among patients diagnosed with CIN2 + lesions, 8 (17.39%) patients were women aged < 30 years. When pathological results were used as a reference, the consistency rate of colposcopy was 61.0% (227/372). Multivariate analyses revealed that age and the type of cervical transformation zone were independent factors affecting the accuracy of colposcopy (P < 0.001).ConclusionsIn countries with limited resources, immediate colposcopy referral should be recommended for patients who are cytology negative but HR-HPV-positive (including non-16/18 HR-HPV-positive), and cervical cancer screening via cotesting should be suggested for women aged < 30 years. Colposcopy has moderate diagnostic value and can be affected by age and the type of cervical transformation zone.

Diagnostic cervical excision in patients with HPV positivity, cytological abnormalities- and preoperative cervical stenosis

AimThere is currently no protocol for classifying patients with HPV persistence and preoperative stenosis of the cervical canal. This has a significant impact on cytology results, colposcopy results and the possibility of obtaining reliable cervical histology outcomes. Our analysis clearly shows that colposcopy and cytology underestimate the histological results in patients with limited visibility due to the presence of a type 3 transformation zone (TZ). Our analysis revealed a significant discrepancy between the colposcopy and cytology results and the histological outcomes. Insufficient colposcopy led to the underdiagnosis of dysplastic lesions in patients with a type 3 TZ and cervical stenosis. In the case of repeated cytological abnormalities and inadequate colposcopy examination, it is crucial to perform a diagnostic conization to exclude high-grade dysplastic changes and cervical carcinoma.MethodsWe conducted a retrospective analysis of 1,021 conizations performed in tertiary care hospital in Wolfsburg, Germany between 2014 and 2020. Of these surgical procedures, 89 were diagnostic conizations. In our analysis, we defined diagnostic conization as a procedure performed when there is HPV persistence and repeated cytologic abnormalities in combination with a type 3 TZ, and when it is not possible to retrieve a relevant cervical histology sample.ResultsIn this period, 8.7% of all conizations were diagnostic excisions. We found histological abnormalities in 48 of 89 patients (53.9%). The histological examination of the excised cone revealed high-grade cervical intraepithelial neoplasia (CIN/HSIL) in 9 patients (10.1%) and CIN 2+ (HSIL) in 23 out of the 89 patients (25.8%). Two cases of early-stage cervical carcinoma (FIGO IA1 and FIGO IA2) were confirmed (2.3%).ConclusionPatients with cervical stenosis, high-risk HPV persistence and repeated cytological abnormalities are at high risk of undetected high-grade cervical dysplasia. Histologic confirmation must be ensured in this patient consultation and this can be achieved by performing diagnostic excisions.

Does HPV-18 co-infection increase the risk of cervical pathology in individuals with HPV-16?

We aimed to investigate differences between HPV-16 mono- and HPV-16/18 co-infections in terms of cervical dysplasia and invasive cancer. This multicentre, retrospective study spanned from December 2017 to December 2020, involving women who visited gynaecological oncology clinics for colposcopy with either HPV-16 or HPV-16/18 positivity. A total of 736 patients, 670 in Group 1 (HPV-16 positivity) and 66 in Group 2 (HPV-16/18 positivity), were compared for the presence of CIN2+ lesions detected by colposcopic biopsy or endocervical curettage (ECC). Exclusions included hysterectomized patients, those with prior gynaecological cancers, and patients with HPV positivity other than types 16 and 18. Among the included patients, 42.4% had a diagnosis of CIN2+ lesions. The cytology results demonstrated abnormal findings in 45.3% in Group 1 and 42.2% in Group 2, with no significant difference between the groups. ECC revealed CIN2+ lesion in 49 (8.7%) patients in group 1, while only 1 (1.7%) patient had CIN2+ lesion in group 2. There was no difference between 2 groups in terms of ECC result (p = 0.052). In group 1, 289 (43.1%) patients had CIN2+ lesion, while 23 (34.8%) patients had CIN2+ lesions in group 2. There was no difference between group 1 and 2 in terms of diagnosis of CIN2+ lesions (p = 0.19). This multicentre retrospective study found no significant differences between HPV-16 mono- and HPV-16/18 co-infections regarding cervical pathologies. Larger studies are needed to validate and further explore these findings.

Advances in human papillomavirusdetection and molecular understanding in head and neck cancers: Implications for clinical management.

Head and neck cancers (HNCs), primarily head and neck squamous cell carcinoma (HNSCC), are associated with high-risk human papillomavirus (HR HPV), notably HPV16 and HPV18. HPV status guides treatment and predicts outcomes, with distinct molecular pathways in HPV-driven HNSCC influencing survival rates. HNC incidence is rising globally, with regional variations reflecting diverse risk factors, including tobacco, alcohol, and HPV infection. Oropharyngeal cancers attributed to HPV have significantly increased, particularly in regions like the United States. The HPV16 genome, characterized by oncoproteins E6 and E7, disrupts crucial cell cycle regulators, including tumor protein p53 (TP53) and retinoblastoma (Rb), contributing to HNSCC pathogenesis. P16 immunohistochemistry (IHC) is a reliable surrogate marker for HPV16 positivity, while in situ hybridizationand polymerase chain reaction (PCR) techniques, notably reverse transcription-quantitative PCR (RT-qPCR), offer sensitive HPV detection. Liquid-based RT-qPCR, especially in saliva, shows promise for noninvasive HPV detection, offering simplicity, cost-effectiveness, and patient compliance. These molecular advancements enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes in HNC management. In conclusion, advances in HPV detection and molecular understanding have significant clinical management implications. Integrating these advancements into routine practice could ultimately improve patient outcomes.

Analysis of molecular marker expression in cutaneous lesions and cervical carcinoma associated with HPV infection.

The study sought to systematically compare the expression of molecular markers in benign cutaneous lesions and squamous cell cervical carcinoma associated with HPV infection to better understand the pathophysiological mechanisms involved in HPV-related lesions and their progression to malignancy. We included 200 patients recruited from a gynecological clinic divided into two groups: 100 patients with positive HPV tests presenting with cutaneous lesions and 100 patients diagnosed with squamous cell cervical carcinoma and testing positive for HPV. The participants were selected to ensure diverse ethnic and demographic representation. The study utilized different statistical analyses, including Chi-square tests to assess associations between categorical variables and logistic regression to evaluate factors influencing lesion progression and compare marker expressions across different lesion types. The results indicated significant differences in the expression of specific molecular markers between cutaneous lesions and cervical carcinomas, highlighting distinct molecular pathways involved in HPV-related lesion development. Notably, markers such as p16, p53, and E-cadherin showed varying expression, suggesting their potential role in distinguishing between benign and malignant lesions. The findings emphasize the significance of molecular marker profiling in improving diagnostic and therapeutic strategies for HPV-related lesions. The differential expression of molecular markers can offer valuable insights into the pathogenesis of HPV-induced lesions and help develop targeted interventions to prevent malignant transformation. Further research is necessary to validate these markers in larger cohorts and diverse populations.

Human papillomavirus vaccine beliefs and intentions Post-COVID-19 vaccine release among mothers in Alabama

PurposeThe current study sought to determine if the release of COVID-19 vaccines influenced Alabama mothers’ attitudes and behaviors regarding HPV vaccination of their adolescent children. MethodsA social media survey was conducted August − September 2022 among mothers of adolescents ages 9–18, who self-identified as Alabama residents and their child(ren)’s primary medical decision maker. The survey assessed demographics, vaccine knowledge and opinions, vaccination history, influences on vaccination decisions, and how COVID-19 vaccine release affected vaccine opinions. Univariable and multivariable analyses were conducted. ResultsOf 241 responses, most participants were white (82.0 %, n = 196), non-Hispanic (96.6 %, n = 230), and privately insured (64.5 %, n = 151), with annual household incomes ≥$61,000 (45.4 %, n = 103). The majority (60.8 %) reported that their child either had or planned to receive the HPV vaccine. The release of COVID-19 vaccines did not change the majority of parental opinions towards HPV, with 78.5 % (n = 161) reporting no change. Among those who experienced a change, 25 % (n = 5) reported an increased likelihood of having their child vaccinated for HPV and 75 % (n = 15) reported a decrease in likelihood. Moderate and high HPV knowledge scores were associated in multivariable analysis with increased likelihood of having their child vaccinated for HPV (“moderate” knowledge AOR: 12.4, 95 % CI: 1.98–78.1; “high” knowledge AOR: 12.8, 95 % CI: 2.00–82.1). Positive HPV opinion scores in the univariable analysis similarly showed increased odds (AOR = 1.5). ConclusionsThese findings indicate that, in this population, COVID-19 vaccine release did not significantly impact subsequent HPV vaccination decision making. Parental perceptions regarding vaccination are critical to informing future interventions.

Investigating the role of Epstein-Barr virus and human papillomavirus types 16 and 18 co-infections in cervical disease of Iranian women.

High-risk human papillomaviruses (HR-HPVs) are known to contribute to cervical cancer (CC), but the role of Epstein-Barr virus (EBV) in this process remains unclear, despite EBV's widespread detection in premalignant and malignant cervical tissues. In this cross-sectional study of 258 cervical samples, including both formalin-fixed paraffin-embedded (FFPE) and fresh cervical tissues, the presence and viral load of HR-HPVs (HPV-16 and HPV-18) and EBV were evaluated in Iranian women with cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), and a cervicitis control group using real-time PCR. The study revealed a significant correlation between disease severity and both increased HPV-16 positivity and HPV-16 and HPV-18 co-infection (p<0.001). Interestingly, the control group had a higher frequency of EBV-positive cases than SCC/CIN groups (p<0.001). HPV-16 DNA load increased with disease severity (P<0.001), while HPV-18 showed no significant difference (P=0.058). The control group had a higher EBV DNA load compared to SCC/CIN groups (P=0.033). HPV-16 increased the risk of CIN II, CIN III, and SCC, while HPV-18 increased the risk of CIN II and CIN III. Notably, EBV was associated with a lower risk of CIN groups and SCC. No significant difference in EBV co-infection with HPV-16/18 was found, failing to support the hypothesis that EBV is a cofactor in CC. However, high EBV viral load in the control group suggests a potential "hit and run hypothesis" role in CC progression. This hypothesis suggests that EBV may contribute briefly to the initiation of CC with an initial impact but then becomes less actively involved in its ongoing progression.