An asymptomatic 40-years old woman had Colonoscopy because of high serum level of CEA. Colonoscopy revealed rectal polypoid lesion 10 mm in size, which endoscopic diagnosis was high grade adenoma or ...intramucosal carcinoma. The lesion was located lower rectum to anal canal, ESD was performed. Resected specimen showed Tubular adenoma with severe atypia in elevated lesion, and anal intraepitherial neoplasia was adjacent to adenoma. She had a history of HPV infection. We should take care AIN during examining anal canal endoscopically, especially a patient have a history of HPV infection.
Human Papillomavirus (HPV), an extensive family of DNA viruses, manifests as a persistent global health challenge. Persistent HPV infection is now firmly established as a significant aetiological ...factor for a spectrum of malignancies. In this review, we examine the latest insights into HPV biology and its intricate relationship with the host. We delve into the complex dynamics of co-infections involving HPV alongside other viruses, such as HIV, EBV, and HSV, as well as the burgeoning role of the microbiome in cancer development. We also explore recent advancements in understanding the specific contributions of HPV in the development of various cancers, encompassing cancers of the anogenital region, head and neck, as well as breast, lung, and prostate. Moreover, we focus on the current preventive strategies, including vaccination and screening methods, and therapeutic interventions that range from traditional approaches like surgery and chemotherapy to emerging modalities such as targeted therapies and immunotherapies. Additionally, we provide a forward-looking view on the future directions of HPV research, highlighting potential areas of exploration to further our understanding and management of HPV and its associated cancers. Collectively, this review is positioned to deepen readers’ understanding of HPV biology and its complex interplay with cancer biology. It presents innovative strategies for the prevention, management, and therapeutic intervention of HPV-associated malignancies.
Abstract HPVs (human papillomaviruses) and other papillomaviruses have a unique mechanism of infection that has likely evolved to limit infection to the basal cells of stratified epithelium, the only ...tissue in which they replicate. Recent studies in a mouse cervicovaginal challenge model indicate that, surprisingly, the virus cannot initially bind to keratinocytes in vivo. Rather it must first bind via its L1 major capsid protein to heparan sulfate proteoglycans (HSPGs) on segments of the basement membrane (BM) exposed after epithelial trauma and undergo a conformational change that exposes the N-terminus of L2 minor capsid protein to furin cleavage. L2 proteolysis exposes a previously occluded surface of L1 that binds an as yet undetermined cell surface receptor on keratinocytes that have migrated over the BM to close the wound. Papillomaviruses are the only viruses that are known to initiate their infectious process at an extracellular site. In contrast to the in vivo situation, the virions can bind directly to many cultured cell lines through cell surface HSPGs and then undergo a similar conformational change and L2 cleavage. Transfer to the secondary receptor leads to internalization, uncoating in late endosomes, escape from the endosome by an L2-dependent mechanism, and eventual trafficking of an L2–genome complex to specific subnuclear domains designated ND10 bodies, where viral gene transcription is initiated. The infectious process is remarkably slow and asynchronous both in vivo and in cultured cells, taking 12–24 h for initiation of transcription. The extended exposure of antibody neutralizing determinants while the virions reside on the BM and cell surfaces might, in part, account for the remarkable effectiveness of vaccines based on neutralizing antibodies to L1 virus-like particles or the domain of L2 exposed after furin cleavage.
Human papillomaviruses (HPV) are the first viruses to have been acknowledged to prompt carcinogenesis, and they are linked with cancers of the uterine cervix, anogenital tumors, and head and neck ...malignancies. This paper examines the structure and primary genomic attributes of HPV and highlights the clinical participation of the primary HPV serotypes, focusing on the roles that HPV-16 and 18 play in carcinogenesis. The mechanisms that take place in the progression of cervical neoplasia are described. The oncogenic proteins E6 and E7 disrupt control of the cell cycle by their communication with p53 and retinoblastoma protein. Epidemiological factors, diagnostic tools, and management of the disease are examined in this manuscript, as are the vaccines currently marketed to protect against viral infection. We offer insights into ongoing research on the roles that oxidative stress and microRNAs play in cervical carcinogenesis since such studies may lead to novel methods of diagnosis and treatment. Several of these topics are surfacing as being critical for future study. One particular area of importance is the study of the mechanisms involved in the modulation of infection and cancer development at cervical sites. HPV-induced cancers may be vulnerable to immune therapy, offering the chance to treat advanced cervical disease. We propose that oxidative stress, mRNA, and the mechanisms of HPV infection will be critical points for HPV cancer research over the next decade.
Abstract Aim To investigate whether the rise during the past decades in the incidence of tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC) and the proportion of human ...papillomavirus (HPV) positive cancer has continued in Stockholm. Patients and methods Pre-treatment biopsies ( n = 252) available from 280 patients diagnosed with TSCC and BOTSCC during 2008–2012 in the County of Stockholm were tested for HPV DNA by a multiplex bead-based assay. Incidence records were acquired from the Swedish Cancer Registry. The data obtained were evaluated together with previous figures from 1970 to 2007. Results HPV DNA was present in 186/252 (74%) of TSCC and BOTSCC biopsies obtained during 2008–2012 in Stockholm. In this region the age-standardised incidence, including the prevalence of HPV-positive and HPV-negative TSCC stabilised 2007–2012 compared to 2000–2006, while for BOTSCC throughout 1998–2012 the same parameters increased moderately ( p < 0.05, for all). In parallel, from 2000 to 2006 through 2007–2012 in Sweden, the age-standardised incidence of both TSCC and BOTSCC continued to rise ( p = 0.012 and p = 0.001 respectively). Conclusion During 2000–2012 the age-standardised incidence and the proportion of HPV-positive TSCC have stabilised at a high level, while the proportion of HPV-negative cancer has remained at a low level in Stockholm, whereas for BOTSCC all parameters are increasing moderately. In contrast, in Sweden the incidence of both TSCC and BOTSCC is still increasing. We hypothesise that the HPV epidemic could be stabilising, first for TSCC, but so far not for BOTSCC, in e.g. some urban areas, while previous trends for both tumours persist at other geographic locations.
Background
Given the disproportionately elevated anal cancer risk in high‐risk populations, it is important to assess the performance of commonly used anal cancer screening tools to improve the ...effectiveness of detection and treatment methods. This study evaluates 1) the concordance between anal cytology and histology results and 2) the performance of cytology and high‐risk human papillomavirus (HR‐HPV) genotyping as screening tools for detecting histologically confirmed anal high‐grade squamous intraepithelial lesions (HSIL).
Methods
Data from the Anal Neoplasia Clinic in Puerto Rico (2014–2021; n = 466) was used. The clinical performance of anal cytology and HR‐HPV genotyping to detect HSIL was compared to the gold standard: high‐resolution anoscopy‐guided biopsy. Sensitivity, specificity, positive predictive value, negative predictive value, and κ coefficients were calculated.
Results
A total of 66.95% of the patients were men, 74.0% were people living with HIV, 76.2% had anal HR‐HPV infection, and 40.34% had histologically confirmed anal HSIL. The weighted κ statistic between the tests (cytology and histology) was 0.25 (p < .001). The sensitivity and specificity of cytology alone to detect anal HSIL were 84.3% (95% confidence interval CI, 78.3%–89.1%) and 36.0% (95% CI, 30.3%–42.0%), respectively. Anal HR‐HPV genotyping had higher sensitivity (92.2%; 95% CI, 87.4%–95.6%) and similar specificity (34.8%; 95% CI, 29.2%–40.7%) compared to cytology. The two tests combined (positive results following cytology or HR‐HPV test) improved sensitivity to detect anal HSIL (97.9%; 95% CI, 94.8%–99.4%), but specificity was compromised (19.2%; 95% CI, 14.7%–24.4%).
Conclusion
Although HR‐HPV genotyping improved the detection of anal HSIL, HR‐HPV testing had lower specificity than anal cytology alone.
The use of anal cytology in combination with HR‐HPV genotyping increased the sensitivity of anal cancer screening.
Highlights • HPV is globally prevalent and related to at least 6 different cancer sites in women and men • Prevention of HPV infections and its consequences is now technologically feasible • Novel ...options for prevention include HPV vaccination and the use of HPV screening methods • Vaccination is cost-effective with high efficacy for HPV infection and disease • International major efforts are needed to extend HPV-related cancer prevention to developing countries
Background: Due to the heterogeneity of existing studies and wide range of human papilloma virus (HPV) prevalence in India, further research into the incidence of HR-HPV and its spectrum of genotypes ...is essential to develop screening policies. This study aimed to determine the incidence and demographic distribution of HR-HPV among cisgender female patients attending a tertiary care facility in North India. Materials and Methods: This study was conducted in the Department of Obstetrics and Gynaecology, SGRR Institute of Medical and Health Sciences, Dehradun, India. HPV-DNA test results of 653 female patients were assessed for HR-HPV positivity, genotyping, and age-based differences via Chi-square analysis. Results: Overall prevalence of HR-HPV was 4.90%, HPV-16 was 1.37%, HPV-18 was 0.76%, and HPV non-16,18 was 2.7%. In patients ≤ 50 years, prevalence of HPV-16 was 0.97%, HPV-18 was 0.38%, and HR-HPV non-16,18 was 2.71%. In patients > 50 years, prevalence of HPV-16 was 2.89%, HPV-18 was 2.17%, and HR-HPV non-16,18 was 2.89%. The difference in the prevalence of HPV-16,18 between patients ≤ and > 50 years was found to be highly statistically significant ( P = 0.007485). The difference in the prevalence of total HR-HPV between patients ≤ and > 50 years was not found to be statistically significant ( P = 0.059905). Conclusion: Our study’s finding of higher HR-HPV positivity rates in patients > 50 years emphasizes the need for continued HR-HPV-DNA-based screening of this cohort. With widespread use in post-menopausal patients, HPV screening can serve as an important armamentarium in the fight against cervical cancer.
Transoral robotic surgery (TORS) has become a more popular technique than transoral laser microsurgery (TLM) for the treatment of oropharyngeal carcinoma (OPC), in particular for human papilloma ...virus (HPV) related OPC. The two techniques differ in terms of the energy source used and the resection philosophy. TLM commonly employs transtumoural cuts to assess the depth of a tumour, whereas TORS usually performs an en bloc resection, avoiding breaching the tumour. This could result in differences in post-operative healing and quality of life (QoL). The ongoing PATHOS trial is recruiting participants undergoing transoral surgery (technique is centre choice) for HPV-related OPC with the aim to analyse the oncological effectiveness of de-intensified adjuvant therapies. The trials’ QoL and functional data pre- and post-surgery present a unique opportunity to conduct this pre-planned sub-study comparing early post-operative functional and QoL outcomes following TLM and TORS.
PATHOS trial participants who underwent TLM or TORS without re-resection or later, staged neck dissection, and who had 4 weeks post-surgery data available were included. The MD Anderson Dysphagia Inventory (MDADI), EORTC QLQC30 and H&N35, and 100mls Water Swallow Test (volume, capacity, speed) were administered pre-surgery and 4 weeks post-surgery. Data on length of in-hospital stay is collected post-surgery and nasogastric tube (NGT) use is collected at 12 months post-surgery.
Data were analysed according to a pre-specified plan using mixed effects cox, linear and logistic regression models that included surgery type, age, anatomical site (lateral vs non-lateral), pathological T-stage, gender, smoking status, pre-surgery scores (for QoL/functional outcomes) and centre as a random effect. For the NGT analysis, only NGTs inserted within 4 weeks of surgery were considered as events and patients who had an NGT inserted pre-surgery were excluded.
Between November 2015 and July 2023, 508 eligible patients were recruited from 40 centres in UK, Germany, France, USA, Australia. 313 (62%) underwent TORS, and 195 (38%) underwent TLM. There was no significant difference in length of hospital stay after surgery between patients undergoing TORS and TLM, when centre was taken in consideration (HR=0.89, 95%CI 0.69-1.16, p=0.401). NGT insertion rates were significantly higher after TORS than TLM (85/189 - 45.0% vs 10/126 - 7.9%, respectively, OR=4.41, 95%CI=1.01-19.3, p=0.049) but there was no difference in duration (median 5 (95% CI=0.5-12) days TLM, 6 (95% CI=4-6) days TORS; HR=1.05, 95%CI=0.52-2.12, p=0.897). Mean scores significantly favoured TLM (relative to TORS) in all MDADI domains and the H&N35 swallowing item at 4 weeks post-surgery (see table 1); between group difference (95% CI): MDADI composite -4.89 (8.27,-1.50), p=0.005; MDADI physical -6.37 (-10.15, -2.59), p=0.001; MDADI global -10.02 (-16.50, -3.54), p=0.002; H&N35 swallowing 7.24 (2.17, 12.30), p=0.005. There was a trend (p<0.1) for difference in EORTC H&N 35 pain score (4.58, 95%CI(-0.90, 9.96), p=0.095) and water swallow capacity (mL/second) (-1.51, 95%CI(-3.11, 0.10), p=0.067) favouring TLM. There was no significant difference between the following scores: EORTC C30 global, constipation, and summary; H&N35 opening mouth, pain killers, and weight loss.
PATHOS presents a unique opportunity to compare two different transoral surgical techniques. In this study population, TORS was associated with significantly higher rates of NGT use, worse H&N35 swallowing scores, and worse MDADI scores at 4 weeks post-surgery compared to TLM. There was also a trend (p<0.1) favouring TLM in H&N35 pain score and water swallow capacity. This is the largest comparative study of functional outcomes following TORS vs TLM. The recruiting institutions’ practices are likely to impact on length of stay and NGT use and has been accounted for in the analysis. This represents a non-randomised, unpowered sub-study for multiple secondary endpoints across which multiplicity was unadjusted. As such the results should be seen as hypothesis generating rather than confirmatory. Furthermore, the study has focused solely on the post-operative recovery period following surgery. It cannot comment on the impact of surgical philosophy (TORS vs TLM) on margins and how this may relate to the PATHOS randomised groups.
Head and neck surgical oncologists may wish to reconsider the role that laser surgery, both as an energy source and a philosophy, has in the emerging field of robotic surgery.
Funded by Cancer Research UK (Grant no: A25317), co-sponsored by Cardiff University and Velindre University NHS Trust.
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