Studies on HPV vaccination alongside surgery were meta-analysed to test effect on burden of disease. Databases were accessed Nov and Dec 2021 . Main outcome measured was: Mean paired differences in the number of surgeries or recurrences per month. Analyses was performed using: Random effect maximal likelihood estimation model using the Stata module Mataan Our results found n = 38 patients, suitable for syntheses with one previous meta-analyses  n = 63, total of n = 101 patients. Analyses rendered an overall reduction of 0.123 recurrences or surgeries per month . Our meta-analyses concludes that HPV vaccine is a beneficial adjunct therapy alongside surgeryRecurrent Respiratory Papillomatosis(RRP) is a rare disease with severe morbidity. Treatment is surgical. Prevailing viewpoint is that prophylactic HPV vaccines do not have therapeutic benefit due to their  The morbidity results from numerous repeated surgeries and can cause scarring of the vocal cords resulting in hoarseness and/or change in voice generation.Recurrent Respiratory Papillomatosis is a rare disease that can have severe morbidity, due to recurrent growth of papillomata that threaten to obstruct the airways. Its aetiology has been clearly defined, and over 90% of cases are thought to be due to Human Papillomavirus (HPV) types 6 and 116 have now demonstrated the efficacy of these vaccines to prevent the development of cervical cancer at the population level. Australia has reported on the impressive reduction of RRP within their highly vaccinated population7, and preliminary data from the US show a similar trend8.The development of the HPV prophylactic vaccines has been a major advance in the field. There is currently a nonavalent vaccine (Gardasil 9—licensed 2014) in use in the US, and the UK is due to change from Gardasil  to Gardasil 9 for its national HPV vaccination programme imminently. Safety profiles and efficacy rates in infection prevention have been similarly excellent. Recent UK data reporting on the national HPV vaccination programme9), but a study in 2015 from 12 European hospitals10 with n = 639, has now demonstrated that there is a trimodal distribution with peaks at median ages of 7, 35 and 64 years of age10.The age at onset of RRP was previously thought to possess a bimodal distribution with juvenile onset (JORRP) and adult onset (AORRP) peaks at approximately 5 and 30 years respectively . JORRP appear to be predominantly via vertical transmission  with a 200-fold increase in risk for mothers with a history of genital wart infection17. However, elective caesarean section to prevent vertical transmission is controversial and has not been shown to definitively reduce transmission19. Early age of presentation with papillomatosis in a child (<3 years) appears to be a risk factor for severe disease and increased recurrences20. Interestingly, infection with the HPV 11 type appears to be associated with more severe disease, more recurrence, distal spread into the larynx, and even malignant transformation22. This is in contra-distinction with HPV 6, which is the dominant type found in ano-genital disease.Reported incidence rates for JORRP and AORRP are estimated at 0.17–1.34 per 100,000 and 0.18–0.54 per 100,000 respectively23 in 1991), and proved highly immunogenic in producing neutralizing antibodies. These discoveries have proved to be the basis of the highly successful L1 vaccines produced in bivalent (Cervarix™), quadrivalent (Gardasil™) and nonavalent (Gardasil 9™) forms and which have been shown to reduce incidence rates of cervical cancer (and dysplastic precursors)6 and also RRP7 in current real world experience.HPV are small (~8 kb) non-enveloped viruses, but have an icosahedral protein capsid formed out of 72 L1 (with monomeric L2 protein embedded within the centre) pentamers. Electron microscopy measurements estimate a virion size of 52–55 nm, and there are 8–10 genes (median of 8) encoded by a double stranded DNA genome. HPV tend to produce papillomata at the transformation zones (where there is transition between squamous and columnar epithelia) but can infect anywhere in the aero-digestive tract or ano-genital mucosa or skin anywhere on the body. L1 protein was found to self-assemble into their native conformation ; dosage sparing via intradermal injections; usage as therapy in combination with a PD1 inhibitor in patients with cervical cancer; efficacy in protecting against recurrent disease in women undergoing ablative therapy for cervical disease, persistence of protection and efficacy in preventing oropharyngeal cancers.There are numerous other L1 vaccine clinical trials ongoing:24. Our group as well as others has published on this interesting observation25 .L1 HPV vaccine has also been used as adjunct therapy in the treatment of RRP. The evidence of efficacy in reducing recurrent papillomata formation, reducing the number of surgeries to keep airways patent, increasing the interval between surgeries, etc. have been accumulating gradually over the years26 which demonstrated beneficial effects of the quadrivalent HPV vaccine, in conjunction with surgery for RRP. Synthesis analyses from 4 published and 2 unpublished datasets yielded 63 patients suitable for meta-analyses at that time. Mean intersurgery intervals (ISIs) improved from 7.02 months (range 0.30–45.0 months) prior to vaccination, to 34.45 months (range 2.71–82.0) post-vaccination. Here we have updated and supplemented the meta-analyses with patients from new studies we were able to find since 2018 to gather the available evidence that HPV vaccine can be used to substantial beneficial effect for RRP . An updated meta-analyses would be most useful in rapid dissemination of this information, since there are likely to be 28,000–150,400 patients (assuming a world population of 8 billion) estimated to be living and suffering with RRP all across the world.There was a meta-analyses published in 2019 by Rosenberg et al.26), we found several studies which were potentially suitable for synthesis analyses. Mauz et al. 201827 and Matsuzaki et al. 201928 were then excluded due to the lack of pre-immunisation data which was required for analyses. Personal communications with Smahelova et al. 202229 allowed us access to unpublished and just published data and has helped to reduce bias. See Table Figure See Fig. n = 12  + 26  + 63  which is n = 101 patients. This equates to an overall reduction of 0.123 recurrences or surgeries per month .Total number of patients included in the analysis was For the Yiu et al. 2018 study, the 12 patients included had a mean recurrence of 0.225 per month (SD 0.221) before vaccination and 0.068 (SD 0.072) after vaccination. For Smahelova et al. 2022, this mean recurrence value for the 26 patients included was 0.098 (SD 0.082) before and 0.028 (SD 0.032) after vaccination. We were able to synthesise these results with those of Rosenberg et al. 2019.26 by providing an updated estimate with increased precision.Our analyses suggest that there is substantial benefit for the intervention of HPV vaccination used as adjunct therapy in conjunction with surgery and strengthen the conclusions of the meta-analysis performed by Rosenberg et al. in 2019Our results support the use of HPV prophylactic vaccination in conjunction with ablative surgery to remove the papillomata, and when more recent studies are combined with the large meta-analysis conducted by Rosenberg et al. 2019, the data lend weight to the argument favouring this intervention for all patients.Further, the mean recurrences for Smahelova et al. 2022 before immunisation might be a little underestimated, due to (1) a less precisely recorded duration of illness (in whole years). Recording duration of illness in whole years prior to vaccination may mean that it was less precise due to rounding up to a whole number, rather than a precisely recorded timespan in months or days. (2) Their data on mean number of recurrences before immunisation is also much lower than in the other studies, which may explain the smaller effect of immunisation. Vaccination appears to reduce the mean number of recurrences to close to zero or low numbers, therefore a smaller average number of recurrences before immunization means that the decline of the decrease line to the average number of recurrences (a low number) after vaccination is not as steep compared to a population with a high average number of recurrences decreasing to a low number.n = 101 patients. This is the largest number of patients meta-analysed from multiple centres so far, and represents a sum total of published and known unpublished data on this therapeutic option. Taken together, the total available evidence strongly suggests there is a substantial benefit for the use of adjuvant HPV vaccine in conjunction with surgery.This latest meta-analysis has now calculated the effect of HPV prophylactic vaccination on the mean RRP recurrences seen before and after vaccination for 30, and that the safety profile of the HPV9 vaccine is consistent with its predecessor HPV4 vaccine. The main benefits of the vaccine would be its proven efficacy in prophylaxis against HPV infection, and thus protection against ano-genital and head and neck cancers, (even if RRP continues to recur). The observations that there are some therapeutic benefits in reducing recurrence of RRP in patients requires quantification, hence this meta-analyses.The risks and side-effect profiles of these HPV vaccines are well known and their safety excellent. The US Vaccine Adverse Events Reporting System (VAERS) has reported and concluded that the vast majority (97.4%) of reported events were non-serious, with syncope and vaccine administration errors the commonest problems despite the millions of doses administeredThe use of HPV vaccine for therapy remains controversial, as the immune mechanisms that would explain this observed phenomenon is uncertain. HPV vaccines are derived from L1 proteins which have self-assembled into virion-like particles (VLPs) and are highly immunogenic but obviously do not contain any HPV DNA so are unable to replicate or initiate infection. The other primary components are the adjuvant , polysorbate 80 (emulsifier) and yeast proteins .The primary function of these vaccines are to produce neutralizing antibody responses against L1 protein, this means that there are high-affinity antibodies generated to bind avidly to L1 protein and neutralise the virus inoculum when contact with the virus occurs. This effect has been shown to be highly effective and long-lasting, and the immune memory generated also leads to an anamnestic response whenever L1 is encountered in the future. Real world data on reduction of cervical cancers and RRP have now been published (as previously mentioned).33. It is important to remember that aluminium adjuvants also carry a risk of adverse effects but have been administered in a multitude of vaccines  to billions of human beings and their safety has been monitored for many decades.Adjuvants included in vaccines are many-decades old compounds shown to augment and increase the immune response to the target, choice of adjuvant can help to increase or bias the immune response to a specific pathway i.e. Th1 or Th2, innate immunity and NK cell function, etc. The ideal adjuvant would increase or ramp up the specificity and amplitude of the desired immune response. Aluminium salts such as AAHS have been shown to increase the immune response via the T helper (Th2 > Th1) pathways and the innate immune system especially through the DAMPs (Damage-Associated Molecular Patterns) “Danger signals theory” and therefore with downstream activation of the adaptive immune system via Dendritic cells (DCs) and macrophagesThe arguments for an adaptive immune response after vaccination with HPV L1 vaccines are two-fold. One, the above use of adjuvant tends to cause a wider and stronger immune response with involvement of both innate and adaptive  immunity to L1 initially, but possibly with involvement of other targets through epitope spreading and affinity maturation later on. Two, we need to remember that HPV 6 and 11 cause primarily productive infections, with full-cycle replication of the viral genome and live virus production. This is in contra-distinction to HPV 16 and 18 (plus other high risk subtypes) which cause productive infections initially but eventually integrate into the cellular genome and cause neoplasia in patients with long-term infections (which were not cleared). This tendency to continuously produce live virus in RRP ensures that viral proteins other than L1 are exposed to the immune response, and can be expected to cause a wide and strong immune response to the pathogenic HPV type since there has been activation of both the innate and adaptive arms of the immune system.34. Use of the quadrivalent L1 vaccine in RRP patients was initially for its predicted prophylactic effect (which has now been confirmed with reduction of incidence rates at population levels) but it is likely that the beneficial therapeutic effect was noticed shortly after more RRP patients began to get vaccinated.The evidence for a beneficial effect in RRP has been accruing slowly over the years since the quadrivalent HPV L1 was licensed in 2006. The lack of therapeutic effect in cervical cancer and its precursors was noted in 2007st recurrence of papillomata, or after an accepted period of time of 3–6 months (whichever is first). Conducting such an RCT is likely to be prohibitive in cost and time, and so far, has not been done. Here in this updated perspective on HPV viral immunology and vaccinology, we have presented the virological and immunological logic behind the observed therapeutic effect, and updated the meta-analyses to include the latest studies (including unpublished) with available and synthesizable data to give increased precision.The most definitive and accepted method of confirming this effect is to conduct a multi-centre randomised double-blinded and placebo-controlled trial with the placebo arm switching over to the HPV vaccine arm after 1This latest tranche of evidence is to provide clinicians in the field, with the most up-to-date knowledge on the benefits versus risks of using HPV vaccine as an adjunct treatment, and therefore for consideration of the inclusion of HPV vaccine as adjunct therapy alongside surgery in national and international guidelines. Implementation of such clinical practice change is therefore likely only in the richer countries of the world to begin with, but implementation of single dose regimes in lower resource countries should be considered.Ethical approval not required. A Population, Intervention, Comparison, Outcome and Study design (PICOS) strategy was undertaken, and patients with RRP looked for. HPV vaccination as adjunct therapy was the intervention searched for. Outcomes were the numbers of recurrences or surgeries before and after HPV vaccination, calculated to the mean recurrences per month. We have taken into consideration the natural history of RRP which tends to a reduction in recurrences and surgeries over time, especially in the young. Therefore, results will be expressed as mean reductions per month, since this is easier to calculate for the shorter pre-vaccine periods seen in young children. We excluded case reports or studies with less than 5 patients as anecdotal single case reports have a high risk of assessment and publication bias. The search terms with inclusion and exclusion criteria are included here.Search terms =  AND  AND (RRP OR recurrent papillomatosis OR recurrent respiratory papillomatosis) NOT  NOT (head and neck cancer OR HNSCC OR squamous cell carcinoma) NOT 29—NCT01375868).Databases searched with the above highly focused search terminology (and Boolean filters). We have also searched through ClinicalTrials.gov for studies which were not included in the Rosenberg meta-analyses. We found one study for which no published data was available at the time (now just published), and we contacted the authors who kindly provided their data .We included only studies for which it was possible to calculate paired differences in the number of surgery or recurrences per month. We excluded study participants for which no pre-immunisation data were available or if patients were directly immunised at clinical diagnosis. This meant that we were able to pool the data of Yiu et al. 2018, with data from Smahelova et al. 2022 for synthesis with the summarised effects obtained by Rosenberg et al. 2019.Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC.). We used a random effect maximal likelihood estimation model using the Stata module Mataan35.Analyses were performed using Stata . Therefore results will tend to represent adults more than children.PICOS and SIGN checklists completed. There is heterogeneity likely due to the following limiting factors for analyses , retrospective data collection). HPV vaccine management in the cohort of synthesised patients were predominantly from HPV4  since the studies were undertaken primarily after the introduction of HPV4 in 2006, whilst HPV9 was licensed in 2014.Meta-analyses statistical methods are recognized for synthesizing different studies with different parameters which can cause significant heterogeneity such as different surgical techniques, concomitant drug administration, even criteria for initiating surgery. A past history of different therapies was not an exclusion criterion. Different surgeons, different centres, different criteria and techniques for surgery were accepted as significant but unavoidable contributors to increased heterogeneity and risk of bias.25. The research questions for that study were developed with their benefit, wellbeing, preferences and clinical experience paramount in our minds. This follow-up study performed meta-analyses and synthesis of available published and unpublished data so was more distant from the patient experience. The parents of the child in Fig. Our RRP patients and the public were initially involved as we planned the interventional study in 2013 which was published in 2017Further information on research design is available in the REPORTING SUMMARY


A 77-years-old man with a 4-month history of progressive functional decline presented after a seizure and brief loss of consciousness.Skin examination revealed red papules on the left abdomen and purpuric patches attributed to idiopathic thrombocytopenic purpura. The red papule was biopsied to help establish a diagnosis . HistopaMagnetic resonance imaging (MRI) revealed punctate frontal lobe infarcts and hyperintense lower thoracic cord signal with cauda equina involvement. Lumbar puncture showed elevated protein with lymphocyte pleocytosis, and laboratory tests revealed no evidence of lymphoproliferative disorder.Question 1: Based on clinical presentation and histopathology, what is the most likely diagnosis?A.Eruptive cherry angiomatosis associated with Multicentric Castleman Disease (MCD)B.Intravascular large B-cell lymphoma (IVLBCL)C.IgA vasculitisD.LymphangiomaE.Kaposi sarcomaAnswers:A.Eruptive cherry angiomatosis associated with Multicentric Castleman Disease (MCD) – Incorrect. Although cherry hemangiomas are present in both MCD and IVLBCL, the hallmark finding of lymphadenopathy in MCD is not present in IVLBCL. The histopathology would demonstrate angiomas without atypical CD20+ cells within the superficial lumens.B.Intravascular large B-cell lymphoma (IVLBCL) – Correct. IVLBCL is characterized by proliferation of atypical CD20+ lymphoma cells within the lumina of small blood vessels, usually without circulating neoplastic cells or extravascular tumors.C.IgA vasculitis – Incorrect. While brain infarcts can occur in vasculitides, IgA vasculitis commonly affects children and presents with violaceous papules and pustules on the lower limbs and buttocks. Histopathology would demonstrate fibrinoid necrosis of the superficial vessels with associated leukocytoclasia and red blood extravasation.D.Lymphangioma – Incorrect. Lymphangiomas are noncancerous fluid-filled cysts in children, usually on the head and neck. Histopathology would demonstrate large lymphatic cisterns that lie deep in the subcutaneous plane and communicate via dilated dermal lymphatic channels lined with endothelial cells.E.Kaposi sarcoma – Incorrect. Kaposi sarcoma presents with violaceous lesions on the body and oral mucosa but the histopathology of KS demonstrates spindled cells with extravasated red blood cells and hemosiderin deposition; HHV-8 is positive in the spindled cells.Question 2: What other cutaneous lesions have been reported and could present with this condition?A.Subcutaneous fluid-filled cyst development on the cheek or neckB.Bilateral leg edemaC.Violaceous papules and plaques on the oral mucosaD.Purpuric papules and pustules with associated ulcerationsE.Nodules and plaques on the trunk or limbsAnswers:A.Subcutaneous fluid-filled cyst development on the cheek or neck – Incorrect. Fluid-filled cysts on the face and neck are characteristic of lymphangioma.B.,Bilateral leg edema – Incorrect. IVLBCL is associated with diffuse, anasarca-like edema of the face, body, and abdomen.C.Violaceous papules and plaques on the oral mucosa – Incorrect. Violaceous spots of the oral mucosa are most closely associated with Kaposi sarcoma.D.Purpuric papules and pustules with associated ulcerations – Incorrect. Purpuric papules and pustules with ulcerations are most closely associated with vasculitis.E.Nodules and plaques on the trunk or limbs – Correct. Forty percent of patients with IVLBCL present with cutaneous features, and of those patients, 49% present with nodules and plaques of the trunk and limbs.Question 3: What is the overall prognosis and treatment of this condition?A.Poor prognosis that should be promptly treated with ruxolitinibB.Poor prognosis that should be promptly treated with R-CHOP  chemotherapy combinationC.Good prognosis that can be further improved by RICE  chemotherapy combinationD.Good prognosis that can be further improved by HAART  agents and chemotherapy combination – such as lamivudine and ritonavir with liposomal doxorubicin or paclitaxelE.Good prognosis that self-resolves, including the skin lesionsAnswers:A.Poor prognosis that should be promptly treated with ruxolitinib – Incorrect. Although IVLBCL has a poor prognosis, ruxolitinib is not used as a treatment for IVLBCL. Ruxolitinib is an appropriate treatment for myeloproliferative disorders, such as myelofibrosis and polycythemia vera.B.,,Poor prognosis that should be promptly treated with R-CHOP  chemotherapy combination – Correct. More than 80% of patients with IVLBCL treated with rituximab-containing combination chemotherapy such as R-CHOP  achieve complete remission.C.Good prognosis that can be further improved by RICE  chemotherapy combination – Incorrect. IVLBCL has a poor prognosis, and although RICE chemotherapy includes rituximab , the ICE combination  is not the most effective treatment for IVLBCL.D.Good prognosis that can be further improved by HAART  agents and chemotherapy combination – such as lamivudine and ritonavir with liposomal doxorubicin or paclitaxel – Incorrect. Although the HAART/chemotherapy combination contains chemotherapy drugs that may treat IVLBCL, the most effective treatment for IVLBCL is R-CHOP. HAART agents with chemotherapy are an appropriate treatment for Kaposi sarcoma.E.Good prognosis that self-resolves, including the skin lesions – Incorrect. IVLBCL has a poor prognosis, and skin lesions may remain or worsen (do not self-resolve).None disclosed.


Chlamydia trachomatis was detected in 59 individuals (8.2%), Mycoplasma hominis in 156 (21.6%), Mycoplasma genitalium in 14 (1.9%), and Ureaplasma spp. in 555 (76.9%); infections with two bacterial pathogens were identified in 73 samples (10.1%). Cervical HPV was detected in 357 out of 1385 samples with a valid HPV typing result (25.8%). The mean age of HPV-positive women was 32.0 ± 8.4 years; individuals testing HPV-negative were slightly older (N = 1028): 34.4 ± 9.2 (p < 0.05). Among the 1371 individuals with valid results both for bacterial STIs and cervical HPV detection, women with an HPV-positive sample were more likely to harbor an STI . Interestingly, bacterial STI positivity illustrated significant heterogeneity between NILM and LSIL cases, with 28.88% of NILM and 46.33% of LSIL cases harboring an STI, respectively (p < 0.05). In brief, in a population with a high prevalence for STIs, especially Ureaplasma spp., an association was documented between bacterial pathogen detection and cervical HPV infection, as well as abnormal cytology; these findings merit further investigation.Prevalent cervical HPV infection and high-risk HPV persistence consequences have been extensively investigated in the literature; nevertheless, any causative interrelations of other sexually transmitted bacterial infections (STIs) with cervical HPV infection have not yet been fully elucidated. This study aimed to investigate the possible association of STIs with cervical cytology aberrations and HPV genotyping results in a representative sample of predominantly young Greek women. Liquid-based cytology and molecular detection for bacterial STIs and HPV as well as extended HPV genotyping were simultaneously assessed in cervical samples from 2256 individuals visiting several urban outpatient Gynecology Departments for well-woman visits or cervical screening throughout a 20-month period. All specimens were centrally processed with validated molecular assays. The mean age of the studied women was 37.0 ± 11.7 years; 722 women (33.30%) tested positive for STI (mean age 34.23 ± 10.87 years). A higher mean age (38.34 ± 11.83 years ( With their long-term reproductive system complications , sexually transmitted infections (STIs) cause significant morbidity in sexually active women, especially adolescents and young nulliparous women, therefore representing a major global health priority ,2. TheseDespite the extensive literature focusing on the consequences of cervical HR-HPV infection, as well as guidelines on STI management that are updated periodically by global stakeholders , the possible interrelationship of other sexually transmitted infections detected concurrently with cervical HPV infection have not been fully elucidated yet ,14,15,16This study aimed to investigate the possible association of STIs with cervical cytology aberrations and HPV genotyping results in a large representative sample of predominantly young Greek women.We conducted a prospective pragmatic  observational study enrolling eligible women who attended outpatient gynecology departments for general gynecological examination or routine cervical screening or colposcopy clinics of urban university hospitals located in 3 different Greek cities (Athens/Larisa/Patras). The study was run throughout a 20-month period (between October 2015 and June 2017). Following detailed briefing regarding the scopes of the study, a Thin Prep cervical sample was obtained from individuals who agreed and signed the informed consent form. Women who were pregnant at the time of enrolment, had any immunosuppressive condition, those who had been previously reviewed in colposcopy for abnormal cytology, or had prior ablative or destructive treatment of cervical precancerous lesions were excluded. We also excluded women who reported ever receiving treatment for any bacterial STI in the past.Chlamydia trachomatis spp. (CT), Mycoplasma hominis spp. (MH), Mycoplasma genitalium spp. (MG), and Ureaplasma urealyticum/parvum spp. (UU/UP)). For these scopes, two validated assays have been utilized:® ).HPV DNA Genotyping .CLARTAccording to the study protocol, detailed history  was obtained from all eligible individuals at the first visit, covering aspects such as age at first pregnancy, parity, number of lifetime sexual partners, recent changes in sexual partners, condom use, and HPV immunization. All women were informed about the scope of the study and were asked to sign a consent form at enrollment. In addition to epidemiological data, other confounding factors affecting HPV status and concurrent CIN (such as smoking) were documented. Consequently, liquid-based cytology (LBC) samples were obtained from all participants using Rovers™ Cervex brushes and transferred into PreservCyt solution. This was followed by centrally performed  cytological and biomolecular analysis of HPV DNA and other bacterial STIs  and subsequently received additional approval from the co-ordinating authority—the Attikon University Hospital Ethics Committee (code: ΕΒΔ 623/14-5-13).The study was conducted within a national multidisciplinary research protocol in cervical pathology and was approved by the Greek Central Government (Ministry of Education and Religious Affairs) under the framework and funding of the HPVGuard research project ; these cases were used in pairs for those parts of the analysis where results were available and valid statistical tests could be obtained  containing the cellular material were used to prepare mono-layer slides using the ThinPrep® 2000 Automated Slide Processor®  according to the manufacturer’s instructions. Cytological results were expressed according to the Bethesda classification system (8): (i) negative for intraepithelial lesion or malignancy (NILM); (ii) atypical squamous cells of undetermined significance (ASC-US); (iii) low-grade squamous intraepithelial lesion (LSIL); (iv) high-grade squamous intraepithelial lesion (HSIL); (v) squamous cell carcinoma (SCC); and (vi) adeno-carcinoma (AdenoCa).Ectocervical and endocervical samples, using the ThinPrepHPV DNA detection was performed on the same biological material implementing a validated molecular assay  capable of identifying individually the 35 most common HPV genotypes, both HR-HPVs as well as several low-risk HPVs (LR-HPVs) .Chlamydia trachomatis (CT), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), and Ureaplasma urealyticum/parvum (UU/UP). DNA was extracted, amplified, and analyzed for the detection and genetic identification of pathogens causing sexually transmitted infections using microarray methods and CLART® STIs kits according to the manufacturer’s instructions . Briefly, 1 mL of the homogenized sample was placed in a sterile 1.5 mL microcentrifuge tube and centrifuged at 12,000 rpm for 10 min to obtain the pelleted form. Subsequently, the supernatant was discarded; the pellet was resuspended in 1 mL sterile water and centrifuged at 12,000 rpm for 10 min. The DNA extraction procedure was followed by the addition of 180 μL lysis buffer T1 and 25 μL proteinase K to the pellet and incubation of the samples in a thermostatic mixer at 56 °C and 550 rpm for 1 h. At the end of the DNA extraction method, 100 µL of eluted DNA was recovered and stored at −20 °C.The samples were tested for bacterial STIs using a DNA microarray system for the detection and molecular identification of pathogens causing sexually transmitted infections. The microorganisms detected were the following: We analyzed cytology results in the aforementioned separate Bethesda-based categories   and corrp value of <0.05 was considered statistically significant. The t-test was used to evaluate the statistical significance for continuous variables (such as patient age) in cases where two groups were considered and data normality was assured. When more than two groups were compared and data normality was also assured, we implemented the ANOVA test and the t-test was used for post hoc analysis. Data were tested for normality by the Kolmogorov–Smirnov test and, when normality was not ensured, the Mann–Whitney U test or the Kruskal–Wallis test was applied . For comparison of categorical variables, the χ2 test was performed and odds ratios were calculated whenever appropriate, i.e., for 2 × 2 contingency tables. All tests were two-sided.The statistical analysis platform used for all tests was based on SAS version 9.4 for Windows software  and a In total, 2256 cases were found eligible for further analysis , since they possessed a valid result in at least one of the three studied tests.p < 0.05). Out of the 722 positive cases, 59 (8.17%) had CT, 156 (21.61%) MH, 14 (1.94%) MG, and 555 (76.87%) UU/UP. Moreover, 73 (10.11%) women suffered from dual bacterial infections; triple or higher order infections were not detected in the study population.One-hundred cases either had invalid results or the biological material was insufficient for adequate testing. Out of all cases with a valid STI detection result, 722 (33.30%) tested bacterial-STI-positive. The mean age of positive cases was 34.23 ± 10.87 yrs and women negative for STIs were about 4 years older, with a mean age of 38.34 ± 11.83 yrs (t-test: p < 0.05). Out of the 35 detectable subtypes, 2 LR-HPV genotypes (26 and 71) were not detected in this cohort; from the remaining, the most frequent were 16 (16.53% of the positive women), 31 (15.97%), 51 (13.45%), 66 (13.17%), 53 (11.00%), and 6 (10.67%) .Out of the 1806 cases with available and valid cytology results, 1373 (76.02%) corresponded to NILM with a mean age of 38.83 ± 12.52 yrs, 86 (4.76%) were diagnosed as ASC-US with a mean age of 32.52 ± 8.52 yrs, 339 (18.77%) were categorized as LSIL with a mean age of 32.07 ± 8.10 yrs, and 7 (0.39%) corresponded to HSIL with a mean age of 40.00 ± 12.88 yrs. Finally, one single SCC case, aged 59, was documented (0.06%) See . Differep = 0.9356). As for STI positivity, this was lower in the older age groups; specifically, 33.33% in the 31–40 group, 21.8% in 41–50 group, 26.19% in the 51–60 age group, and, finally, 12.5% in the senior, 61–70 age group (see p < 0.001). Similarly, HPV positivity percentages were waning in the older age groups (Focusing on the subgroup of the 58 women of the youngest age (≤20 yrs) for whom a valid STI and an HPV test were both available, 23 (39.66%) had a bacterial STI detected. There were no significant differences in the proportions of infected individuals between the ≤20 yrs group and the 21–30 yrs group (roup see . Differee groups .Ureaplasma spp. (UU/UP) gradually decreased with advancing age  were mostly prevalent (22.41%) in the youngest age group (≤20 yrs) and less common in older age groups, specifically 15.9% (21–30 yrs), 12.07% (31–40 yrs), 8.65% (41–50 yrs), and 7.14% (in the 51–60 yrs); indeed, coinfections were not documented in ages 60+ . HPV-poscing age . Howeverp < 0.05) (p < 0.05). For the sub-population of HPV-positive cases, no significant differences in the STI status were observed among the cytological subcategories; however, for the HPV-negative sub-group, bacterial STI positivity rate was higher in the LSIL group than in NILM cases  . Comparap < 0.05), while this risk decreased in STI-negative women . In cases with unknown/unavailable HPV status, cases testing positive for bacterial STI were linked with abnormal cytology . Women testing positive for both an STI and HPV had a higher chance of concurrent cytological abnormalities , while patients negative for both HPV and a bacterial STI illustrated higher chances of normal cytology than cases harboring either or both  infection types  had NILM cytology. ASC-US was identified in 21 (6.78%), LSIL was detected in 162 out of 309 (52.43%), and HSIL in 5 (1.62%) . Out of p < 0.05); a similar situation was observed when we studied women with HR-HPV infection (irrelevant of the LR-HPV infections) or LR infections (irrelevant of HR infections) (see p < 0.05).Out of the cases with valid STI results as well as HPV detection outcomes (n = 1371), CT was detected in 35 (7.61%) patients, MH in 99 (21.52%), MG in 11 patients (2.39%), while UU/UP was detected in 350 (76.09%) patients . HPV-posons) see . Interesp < 0.05) and a stronger correlation with LR- than HR-HPVs . Ninety-nine women (7.22%) were positive for MH; the odds ratio of its association with HPV ranged between 1.95 and 2.45 , which illustrated the strongest correlation with HPV positivity  to HR-HPV-related  or simultaneously LR- and HR-HPV-related   women tested positive for UU/UP; for these women, the risk of UU/UP positivity increased as the infection switched from LR-HPV-related  see .Ureaplasma Spp. in particular), illustrating cervical HPV prevalence and genotype distribution consistent with previously reported epidemiology in a national setting, we have documented an association between bacterial pathogen detection and HPV infection as well as abnormal cervical cytology [In this study, in a European population with relatively high bacterial STI prevalence  (biotype 1) und U. urealyticum (UU) (biotype 2) [In this multicenter molecular epidemiology study, which recruited representative cohorts of reproductive-age women, the largest materialized in Greece so far, simultaneous infections by bacterial STIs together with cervical HPV have been frequently detected. The distribution of HPV genotypes in this large multicenter cohort is consistent with the findings of previously reported studies conducted by our group . Ureapla decades ,22,23,24n nature . It can otype 2) .Ureaplasma spp. is endemic in Greece, as is the case with other geographical areas. In this perspective, our study’s findings might reflect regional bacterial STI variability. In a previous study also focusing on the possible association of HPV and STI codetection with cytological findings, Parthenis et al. recruited prospectively 345 asymptomatic patients attending a Greek urban gynecology clinic for routine cervical screening [Ureaplasma spp., detected in 18.2% of participants, was the most frequently isolated pathogen; one in every four women in this study testing positive for this bacterium additionally harbored an HR-HPV genotype. In another contemporary Greek study, comprised of 347 asymptomatic women undergoing routine cervical screening in an urban setting, 16.13% of the studied individuals carried Ureaplasma spp. (predominantly UP) in high concentrations [Despite the absence of formal nationwide data, the literature clearly suggests that creening . In thistrations .Ureaplasma spp., MH, and MG were more common in patients with warts, with 45.9% of individuals among this cohort being diagnosed with Ureaplasma spp. [In a different setting, that of an urban Greek STD outpatient clinic, Mortaki et al. conducted a cross-sectional study in which cervicovaginal smears of women with anogenital warts were examined for the presence of HR-HPV types and common STIs. In contrast with CT coinfection rates, which were similar across the study groups, the authors report that coinfections with sma spp. . Finallysma spp. .Other studies from neighboring countries have also investigated the concurrent detection of cervical HPV together with bacterial STIs. In a recent Italian study, Martinelli et al. documented a relatively high percentage of women with CT infection, alone or in combination with seven HR-HPV types, in individuals attending gynecology outpatient clinic following an abnormal Pap smear . AnotherThere is ample literature evidence that, in addition to the key role of HR-HPVs, cervical carcinogenesis is also associated with inflammation ,33. InteChlamydia trachomatis (CT) cervical infection have been suspected for decades; currently, the association between CT and CC has been well established [Among bacterial STIs, the detrimental effects of ablished ,39,40,41ablished ,37,42. Iablished .Ureaplasma spp. are common STI pathogens frequently found in the healthy female genitourinary tract; therefore, their pathogenic role in individuals is difficult to substantiate [Ureaplasma spp. infections might favor the entry of other microorganisms, act as cofactor in the pathogenesis of cervical disease, or induce chromosomal alterations that might lead to carcinogenesis of epithelial cells [tantiate ,43. In atantiate . Drago etantiate . The chral cells . The posal cells ,46. The al cells ,47,48.Ureaplasma spp. vaginal colonization at low levels is seemingly harmless [Ureaplasma bacterial load as a diagnostic criterion might be required to decide on appropriate drug intervention [Ureaplasma, as is also the case for MH [From a microbiome perspective, harmless . In the harmless . Similarharmless . This isrvention ,52. In oe for MH .The study of Veteramo et al. also evidenced the lack of protective precautions against STIs, both in HPV-positive and HPV-negative women. Despite the debate on the effectiveness of condoms in reducing HPV transmission rates, counseling on STI prevention use should be continued to prevent bacterial pathogen transmission ,54.With their range of severe negative adverse reproductive consequences, early detection and treatment of bacterial STIs in the susceptible population seems all-important. However, several factors contribute in suboptimal STI control globally  ,56,57.Interestingly, there is currently no unanimity in viewpoints and guidelines for STI detection screening policies . A positUndeniably, cost-effectiveness appraisal of bacterial STI screening policies is multi-factorial, linked with several mid- and long-term social and public health correlates, frequently disregarded by mathematic modeling. Certainly, reliable diagnosis by the novel multiplex RT PCR assays offering simultaneous detection of cervical pathogens largely facilitates their management nowadays ,60,61. FWith 2256 individuals enrolled in the analysis, this study’s major strength is predominantly the sizable patient sample. Our study represents the largest relevant prospective work conducted in Greece so far. Furthermore, all cytological and molecular assessments  have been performed in a single university-affiliated laboratory (thus minimizing variability), implementing state-of-the-art molecular assays and undergoing regular external QA. The extended HPV genotyping assay utilized in this study allows for the detection of subtle differences in the interaction of specific bacterial STIs with either LR-HPVs or HR-HPVs in a subsequent work.Trichomonas spp. Or Candida that may have an additional role either as true pathogens, facilitators, or commensals [The main limitation of this pragmatic  study is the incomplete dataset of assays affecting several individuals, with missing results either for cytology, a particular bacterial STI, or for HPV assessment . Furthermmensals ,63. Aftemmensals . Fourth,mmensals ,54. FiftUreaplasma spp. and/or other STIs are real cofactors or are just “followers”, taking advantage of the immune tolerance and abnormal regulation of the cell cycle control generated by HPV for the high prevalence of STIs found in HR-HPV-positive women [With a host of complex interrelated mechanisms, HPV and bacterial STIs cause detrimental effects on female fertility as well as significant psychosomatic burden imposed by the disease and the related treatments. Several physicians and authors indeed consider their codetection an anticipated finding, since both STIs and HPV represent sexual exposure correlates . Most live women .With vaccinated cohorts gradually entering cervical screening, future studies will investigate the long-term public health effects of HPV vaccination on bacterial STI prevalence at the population level . Despite


There is limited availability of self-management interventions for oesophageal cancer survivors at present. This study examined the feasibility of OptiMal, a six-week, self-management programme to improve fatigue, mood and health-related quality of life for oesophageal cancer survivors.A mixed methods design was used to evaluate the feasibility of OptiMal. The quantitative arm of the study examined changes in the Multidimensional Fatigue Inventory, Hospital Anxiety and Depression Scale, and the EQ-5D-3L, administered prior to OptiMal (T1), immediately following completion of OptiMal (T2), and three months following completion (T3). Qualitative inquiry in the study was guided by a qualitative descriptive approach through focus groups investigating the experiences of group participants, and individual semi-structured interviews at T3. Qualitative data were analysed using thematic analysis.Two OptiMal programmes were delivered over a six-month period with a total of fourteen individuals who had finished treatment for oesophageal cancer. The attendance rate was 89.3%. Statistically significant reductions were observed in fatigue, difficulty performing usual activities, anxiety and depression at three-month follow-up. Qualitative findings identified acceptability of the content and delivery format of OptiMal. Participants reported applying self-management strategies acquired through OptiMal to increase participation in daily activities and improve their health and well-being.This feasibility study yielded promising results in terms of self-management outcomes for oesophageal cancer survivors following attendance of OptiMal. Larger scale research studies with control groups are warranted to examine the outcomes in a robust manner. In Ireland, 6706 cases of oesophageal cancer were reported between 2000 and 2017. Treatment for oesophageal cancer often involves surgical intervention, along with chemotherapy and radiation therapy. Oesophageal cancer has been associated with slow recovery and poor prognosis. Many oesophageal cancer survivors experience post-operative complications, with longer-term impact on fatigue and energy levels, mental health and participation in daily life. As more individuals are living with and beyond oesophageal cancer, it is important to support patients with managing persistent effects of cancer and treatment and to participate in daily life. In line with a survivorship approach, there is increasing recognition that oesophageal cancer survivors can benefit from supports following surgery to transition to life post-treatment and build a satisfying daily routine.Oesophageal cancer presents a variety of complications for health, well-being and participation in daily life activities. The prevalence of oesophageal cancer appears to be growing, with reports estimating it to be the sixth most common cause of death by cancer.68 The impact of fatigue may decrease over time, Djärv and colleagues (2008) found that participants reported reduced fatigue three years post-surgery, when compared to 6 months post-surgery. Tsou and colleagues outlined that fatigue is often one of the most significant and poorly controlled symptoms of cancer, or cancer treatment, and that it often results in other difficulties such as disturbed sleep, reduced attention and other functional impairments. Schandl and colleagues reported that oesophageal cancer survivors experienced a wide variety of difficulties related to eating, nutrition and digestion in the year following oesophageal cancer surgery. Several studies have reported that reflux can persist for over 1 year post-surgery, along with symptoms such as dry mouth and dyspnoea, qualitative studies describe difficulties with eating following surgery, issues with constipation or diarrhoea, and weight loss, nausea, bloating or digestive difficulties.12Post-operative complications and persistent symptoms such as fatigue and distress are common following completion of oesophageal cancer treatment. Fatigue is frequently reported with 41–60% of oesophageal cancer survivors experiencing significant fatigue in the post-surgical period, persisting for over 12 months for many survivors. The incidence of anxiety and depression appears to peak shortly after completion of surgery, with studies reporting between 40% and 63.3% of participants meeting the criteria for probable anxiety or depression.15 Schandl et al reported that 11% of their participants reported clinically significant symptoms of anxiety, and 12% of participants reported clinically significant symptoms of depression in the year following surgery. However, Liu and colleagues reported clinically significant symptoms of anxiety or depression in up to 23.3% of their participants in their study of psychological distress and Health-Related Quality of Life (HRQoL) 2 years post-surgery.Anxiety and/or depression appear to be common amongst oesophageal cancer survivors, particularly within 1 year of diagnosis and treatment.17 following treatment. Qualitative studies lend support to these findings, describing the impact of psychological distress in the recovery period from oesophageal cancer, with many participants identifying the impact of fear of cancer recurrence and pain during post-operative period.Psychological distress and decreased energy levels have a significant impact on the health and well-being of oesophageal cancer survivors, and have been cited as predictors of poorer survival An exercise intervention with a 12-week brisk walking programme and dietary education yielded positive outcomes for reflux symptoms, anxiety and sleep quality. A nursing led series of education and counselling sessions that focused on nutrition for oesophageal cancer survivors in the post-surgical period was helpful in enabling patients to understand physical changes following treatment and managing nutrition. Currently, support programmes that cater for oesophageal cancer survivors in the post-treatment period tend to target specific topics such as nutrition or exercise. However, there is limited evidence of self-management programmes to support oesophageal cancer survivors to participate in meaningful daily life activities, and to manage persistent symptoms or effects of oesophageal cancer.Survivorship supports for oesophageal cancer survivors are continuing to emerge. A nursing led intervention that included patient education, health management and healthy lifestyle habits, reported positive outcomes for self-care ability, social relationships, and anxiety and depression amongst those who participated in the intervention when compared to a control group.2124 The purpose of this study therefore, was to explore the feasibility of OptiMal for oesophageal cancer survivors. The specific objectives included:• To examine the feasibility of OptiMal as a multidisciplinary self-management intervention for individuals with oesophageal cancer• To examine participant-reported changes in fatigue, anxiety, depression and HRQoL following participation in OptiMal• To explore participants' experiences and acceptability of OptiMal • To explore application of knowledge of symptom management from OptiMal into daily activities following completion of the programmeOptiMal is a group-based, self-management intervention that focuses on providing individuals with skills and confidence to manage persistent symptoms of fatigue and distress and facilitate participation in daily activities. It was initially developed for people with multimorbidity and then adapted for use with women with breast cancer. OptiMal is facilitated by an occupational therapist with physiotherapy and dietician input on physical activity and nutrition.OptiMal is based on self-management support theory to increase individuals’ knowledge and skills to manage long-term health conditions. It is underpinned by Bandura’s theory of self-efficacy. The original OptiMal programme was designed to meet the needs of people with multimorbidity within a primary care context. Each week also includes goal-setting activities to enable participants to implement learning during and after completion of the programme. Lorig et al. recommend weekly goal-setting to facilitate effective application and sustainability of self-management skills. All participants receive a handbook that contains information on each of the weekly topics, a copy of the slides presented each week and goal-setting templates. OptiMal was delivered in the academic institution in which the authors are located.The programme consists of 6 group-based sessions delivered in-person over the course of 6 weeks for 2.5 hours/session. Programme content focuses on management of persistent symptoms commonly experienced by individuals with oesophageal cancer. These include fatigue, distress, reduced exercise tolerance and difficulty with weight management. Two OptiMal programmes were delivered during the study period. Fidelity of the intervention was monitored by one of the authors (DC), who is an occupational therapist, and who facilitated both programmes. A weekly log was completed to record changes to content and/or delivery format following each session. DC was also present at the physical activity and nutrition sessions to note any changes to intervention content and delivery. The same physiotherapist and dietician delivered the physical activity and nutrition sessions in both OptiMal programmes delivered over the study period. There were no significant changes to content and/or delivery format across the two programmes. The research was guided by the Medical Research Council Framework for complex intervention research, which is concerned with examining whether interventions are generalisable, and feasible to implement. This study examined the feasibility and acceptability of OptiMal, in order to inform the next stage of evaluation. The reporting of this study conforms to COREQ guidelines for qualitative studies and CONSORT statement extension for feasibility studies.This feasibility study utilised a mixed methods design. The quantitative phase was a pre-test, post-test design, while the qualitative phase used a qualitative descriptive design as outlined by Sandelowski. stated that although a sample size justification is important for feasibility and pilot trials, a formal sample size calculation may not always be appropriate. OptiMal had previously been tested for individuals with different types of cancer, however, that study did not include individuals with oesophageal cancer who have unique needs regarding self-management of post-treatment symptoms. Therefore, as the primary purpose of this study was to examine the acceptability of OptiMal for people with oesophageal cancer, a sample size was not calculated.Billingham et al.,Inclusion criteria for this study were individuals aged over 18 years of age, who had completed treatment for oesophageal cancer. Participants self-selected for this study based on self-identified need for education and support to manage post-treatment difficulties. Information regarding OptiMal, and the aims of the study, was presented at an oesophageal cancer education day hosted by a national voluntary cancer organisation that supports oesophageal cancer survivors in Ireland. Individuals were invited to express interest in participation in the study. Those who signed up to participate were contacted by a member of the research team following the education day. An appointment was made with interested participants to attend the study site to provide informed consent and complete study measures. Prior to obtaining written consent, the researcher explained the purpose of the study and answered any questions participants had about OptiMal and/or the study. It contains fives subscales: general fatigue, physical fatigue, reduced activities, reduced motivation and mental fatigue. Higher scores indicate higher levels of fatigue. The MFI has been validated for use with cancer patients and has demonstrated good internal consistency and construct validity.The Multidimensional Fatigue Inventory (MFI) is a 20 item, self-report instrument that gathers data regarding multiple aspects of fatigue.33 The tool includes an anxiety and depression subscale. Higher scores indicate increased probability of clinically significant symptoms of anxiety or depression. The HADS is widely used in research and clinical practice, and has demonstrated internal consistency, and content validity when used with cancer patients in specific contexts.34The HADS is a 14-item self-report instrument that gathers data related to possible presence of anxious or depressive states in non-psychiatric settings. The measure consists of two parts. The first part of the measure gathers self-reported data in relation to mobility, self-care, performance of usual activities, pain and anxiety/depression. The second part of the measure consists of a visual analogue scale (EURO-VAS) where respondents rate their current health status (0–100), with higher scores indicating better health. The EQ-5D-3L has demonstrated good test-retest reliability and validity amongst cancer patients.The EQ-5D-3L is a measure of health status developed by the EuroQol group.Data were gathered at three time points during the study: prior to commencing OptiMal (T1), immediately following completion of OptiMal (T2), and three-months following completion of OptiMal (T3). T1 data were collected during the initial meeting between individual participants and a member of the research team, prior to commencement of OptiMal. Participants completed and returned T2 questionnaires in the final week of OptiMal. Three-month follow-up (T3) questionnaires were either emailed or posted to participants (with self-addressed envelope) based on participant preference.Statistical analysis was completed using the Statistical Package for the Social Sciences (SPSS) v.27. A cut-off point of P ≤ .05 was used to establish statistical significance in all analyses. Data were analysed using frequency and descriptive analysis to generate a demographic profile of study participants. Non-parametric statistical techniques were used given the sample size, and that not all data were normally distributed. Wilcoxon signed rank tests examined differences in MFI, HADS and EURO-VAS scores at T1, T2 and T3. Frequency analysis was used to explore trends in EQ-5D-3L scores at all time points. Chi square tests for independence examined differences in EQ-5D-3L at T1, T2 and T3. Where no differences were reported, variables were excluded from chi square tests. Fisher’s exact test values were reported given the small sample size. Focus groups were carried out in the final week of OptiMal to gather participants’ experiences of attending OptiMal, the impact of OptiMal on self-management of persistent symptoms, relevance of content, and suitability of delivery format. In order to explore the longer-term impact of OptiMal on symptom management, semi-structured interviews were conducted with a convenient sample of three participants by telephone, three months following completion of OptiMal. Focus groups and interviews were carried out by senior author, DC, who has considerable experience in qualitative research. Interview guides used for the focus group and follow-up interviews were the same as those used in previous OptiMal studies  coded both focus groups and all follow-up interviews separately. They then met to compare their assigned codes. This process involved identifying similar codes and discussing their rationale for assigning these codes to relevant passages of text. Differences in codes were also identified. The two authors then discussed their rationale for assigning the different codes and reached agreement on whether to retain the codes and/or to rename them. Where agreement could not be reached, the third member of the team (NA) was invited to assist with reaching a consensus. Following agreement on all codes, the two authors (EK and DC) then grouped the codes into categories and created themes as recommended by Braun and Clarke. Transcripts and a summary of findings of individual interviews were returned to interviewees to enable them to remove any information given, or to amend summaries of their transcripts. None of the participants made any changes to either their transcripts or summaries.Focus groups and individual interviews were audio-recorded and transcribed verbatim. Transcripts were then uploaded to NVivo computer software for analysis of qualitative data. Qualitative data were analysed using Braun and Clarke thematic analysis.Ethical approval for the study was obtained from St James’ Tallaght University Hospital Ethics Committee, reference number: 2014-12 Chairman’s Action (12). Informed consent was obtained from all participants in writing prior to commencing the study. Data were managed in line with General Data Protection Regulation (GDPR) and Health Research Regulations (2018) requirements.The number of attendees at the national education day was 134 individuals. However, this included people with oesophageal cancer, family members and healthcare professionals. It was not possible to specifically identify how many people with oesophageal cancer were in attendance. A total of 24 individuals expressed interest in participation in the study and provided contact details. These individuals were contacted by a member of the research team and further information on OptiMal and the study was provided. Based on the maximum number of participants for OptiMal,  2 programmes were delivered over a 6-month period. Those who agreed to participate were asked to indicate their availability and preference for attending OptiMal.All 24 individuals who provided contact details met the eligibility criteria and of these 16 agreed to participate in the study, giving a recruitment rate of 66.8% from those who indicated interest. Reasons for non-participation included timing of the programme and travel difficulties to study centre. Seven people opted to participate in the first OptiMal programme and nine opted for the second programme. Two participants withdrew from the study after the first week of OptiMal (1 from each programme). All other participants completed the study giving a retention rate of 87.5%. Reasons for withdrawal were illness and personal reasons. Fourteen participants (six from the first programme and eight from the second programme) completed baseline and follow-up outcome measures. There was a mean attendance rate at both programmes of 89.3% with eight participants (57.1%) attending all 6 weeks of OptiMal.The majority of participants were male , married  and living with another person . Participants’ ages ranged from 51 to 73 years at time of participation in the study, with a mean age of 61.6 years (SD 5.73). The majority of participants were not working at the time of the study . See All participants had completed cancer treatment at time of commencing the study. The mean time since completion of cancer treatment for participants was 3.69 years (SD 4.27) with a range of 4 months to 17 years. Treatment included surgery , chemotherapy  and radiation therapy .Statistically significant improvements were observed in total MFI scores from baseline (T1) to three months (T3) following participation in OptiMal, . No statistically significant differences were observed for MFI total scores between T1 and T2 see . IndividThere were no statistically significant improvements in either anxiety or depression between T1 and T2 . HoweverThere was an overall trend of improving scores in the Euro-QoL visual analogue scale from T1 to T2 and from T1 to T3, however, this did not reach statistical significance .The EQ-5D-3L has five health states  and three scoring categories: no problem, some problems and extreme problems. For purposes of analyses, the number of individuals reporting ‘some problems’ and ‘extreme problems’ were combined and compared with the proportion of individuals reporting ‘no problem’.A Chi square test for independence indicated significant differences in the proportion of participants experiencing ‘some/extreme problems’ with ‘Usual Activities’ between T1 and T2, χ2  = 5.49, P = .02. This significant difference was also observed between T1 and T3: χ2  = 4.98, P = .02. Although there was a trend towards a decrease in the proportion of participants experiencing ‘some/extreme problems’ in the other two health states of ‘Pain’, and ‘Anxiety/Depression’ over time, no statistically significant differences were identified . The catIn order to gather participants’ perspectives on the format, content and impact of OptiMal, two focus groups were facilitated with participants who attended the final session (i.e. Week 6) of each OptiMal programme. All five people who attended OptiMal on Week 6 participated in the first focus group, and all seven people who attended OptiMal on Week 6 participated in the second focus group. Duration of each focus group was 42 and 51 minutes, respectively. Semi-structured individual interviews were conducted with three participants three months following completion of OptiMal to explore longer-term application of the programme to daily life. Individual’s interviews were between 40 and 66 minutes in duration.On combining data from the focus groups and the three individual interviews, two themes were identified following thematic analysis: ‘Impact of OptiMal’ and ‘Acceptability of OptiMal’. In the first theme, participants identified benefits to intrapersonal skills such as increased confidence and motivation. They also identified how participation in OptiMal facilitated increased participation in valued daily activities. In the second theme, participants discussed their opinions on the acceptability of the content and format of OptiMal. Three sub-themes were identified within this theme: (i) Intrapersonal benefits of the OptiMal programme which included increased confidence and empowerment (ii) Participation in daily activities where participants identified re-engaging with a range of activities following participation in OptiMal and (iii) implementing self-management strategies to improve health.I have gained an awful lot of knowledge in all areas. The knowledge I’ve gained each week, I’m going to bring that forward with me. I kind of feel I was floating along, just going through daily life. But each week I’ve gained knowledge from the course”(FG) “In the focus groups and interviews, participants described various positive benefits of the programme in terms of psychological well-being including increased confidence, motivation, resilience, and agency and control over one’s health. Knowledge obtained during OptiMal enabled greater understanding and acceptance of participants’ health needs, and the longer-term effects of cancer and treatment. Participants also reported being more informed about how to manage their health following attendance at OptiMal:One participant outlined how they believed they can manage their health effectively following participation in OptiMal and plan to continue to use goal-setting after the programme. Approximately four participants reported being more confident following OptiMal, and that the knowledge gained from OptiMal enabled them to try new exercise programmes.I needed something to give me a kick in the bottom to get on with life as best I could.” “Participants also discussed the importance of motivation, and many reported being more motivated to manage their health:It set me on the road to exercise again which I hadn’t been doing”(FG): “Participants described returning to previously valued activities, and trialling new activities following completion of OptiMal, including leisure and work activities.Getting up in the morning, putting on my uniform, getting my lunch ready. I’m back to two days. I forget I have cancer.” “Another participant reported having returned to work following completion of OptiMal and how this helped him to reduce his focus on having cancer.However, finding a balance of participating in activities and managing fatigue was a challenge reported by some participants.Being mindful of my fatigue. Being mindful of my body and realising which time of the day is the best for me and accepting that it’s okay not to have everything done in one day” “Participants discussed applying their learning from OptiMal to their daily activities particularly in relation to fatigue and energy management. One interview participant summarised her key learning regarding energy management.You need to plan for the different weeks your exercise, motivation, cognitive, mental… actual concrete plans”(FG): “Fatigue management strategies, acquired during OptiMal, such as forward-planning and goal-setting were reported as facilitators for applying learning from OptiMal into everyday activities.I’m more inspired to get my energy levels up. Whereas before the course I was just plodding along saying “Oh I’ll get better with time”. But now I’m more conscious now of all these things that are going to improve my health”(FG) “One participant outlined how the programme content provided insight on how to improve health and increase energy levels:In this theme, participants discussed the relevance and usefulness of OptiMal for individuals with oesophageal cancer. They discussed their experiences of the 6-week format of OptiMal and delivery methods used by the facilitators. They also identified benefits of meeting others with oesophageal cancer and learning from each other.I think its fine, six weeks is long enough…and the length of sessions is fine, any longer you’d be just too tired”(FG): “Participants reported positive perceptions of the format and structure of OptiMal. All participants unanimously agreed that a 6-week course of 2.5 hours was an appropriate length and duration.I think to get on a course like this within six months of having your treatment, or your operation, would be a great idea”(FG): “On discussing the most suitable time to attend OptiMal, eight of the 12 focus group participants reported that it would be ideal to avail of a programme like OptiMal approximately six to nine months post completion of cancer treatment.Other participants reported dissatisfaction with high cost of parking charges and recommended hosting the programme in a location that was easily accessible.Just to say how wonderful the course was and that please God it keeps going because I felt it really did me the world of good” “Overall, all participants reported positive experiences of OptiMal, and some participants reported that they would like to do a refresher course in the future to assist them with implementing the content into their daily lives:Participants were satisfied with how the group was facilitated, with ample opportunities for participants to contribute to weekly discussion topics and reported being satisfied with the relevance and usefulness of OptiMal content. They particularly valued content related to exercise, eating, looking after their mental health and well-being, and communicating with healthcare professionals and family. All participants are provided with a handbook summarising the programme content. They reported that the handbook was useful both during the group sessions and as reference material upon completion of the programme. Some participants suggested additional time for some of the topics covered such as nutrition and managing mental health, and recommended including a talk from a gastroenterologist.Goal-setting is an important aspect of the OptiMal programme to facilitate application of learning, with goals reviewed on a weekly basis. Examples of goals identified by participants during OptiMal included trialling fatigue management strategies, increasing physical activity levels and re-engaging with leisure and social activities such as taking holidays with family and friends.I think one of the main benefits that I got from the course was setting goals each week… You had to actually keep it going and that applied to all the sessions that we had the goal”(FG): “In both the focus groups and individual interviews, participants discussed how they valued the process of setting and reviewing goals during OptiMal to maintain focus and apply their learning from the weekly OptiMal sessions:And it did really push me. I possibly wouldn’t have done it had I not got the course to set my goal” “Another participant discussed how goal-setting motivated her to persist with her goal of travelling:Many participants discussed the importance of coming together as a group of oesophageal cancer survivors, and the sense of shared understanding of their experiences of receiving a cancer diagnosis, having treatment and survivorship. Participants reported reassurance in discussing symptoms with other group members. Existing programmes to support oesophageal cancer survivors tend to focus on nutrition or exercise, and evidence is needed on the impact of holistic approaches to self-management. In this study, improvements were noted in fatigue, anxiety and depression three months post-completion of the programme. Statistically significant reductions were also observed in the proportion of participants reporting difficulties with participation in usual activities three months post-completion of OptiMal. Qualitative findings lend greater insight into how participants utilised self-management strategies acquired from OptiMal, to increase their participation in daily activities and support their health and well-being.Availability of self-management programmes to support oesophageal cancer survivors is limited at present. Participants greatly valued goal-setting processes and peer support during OptiMal. They also valued sharing their experiences with other oesophageal cancer survivors, learning from each other, and reported a sense of being understood. Previous studies examining the acceptability of OptiMal for cancer survivors also reported positive experiences of the content and delivery format of the programme. Therefore, the findings of this study suggest that OptiMal is adaptable for survivors of different cancer types. The weekly content of OptiMal focuses on a range of persistent symptoms experienced by cancer survivors. These include fatigue, distress and anxiety and cognitive difficulties. Many studies have identified the impact of these symptoms across many different cancer types. OptiMal focuses on providing individuals with strategies to manage persistant symptoms and reduce their impact on daily roles and activities. Previous studies of OptiMal have demonstrated effectiveness for individuals with a range of chronic diseases.23 Therefore, as cancer is now considered a chronic disease, research on OptiMal to date indicates promising application of this self-management group-based intervention across different cancer types.Participants reported mainly positive experiences of OptiMal, in terms of the content, format, resources and structure of the programme. Retention and attendance rates at each of the weekly OptiMal sessions were high, and participants shared positive feedback regarding acceptability of the programme. Some participants had to travel long distances to attend the weekly sessions but attended each week because they reported the group was important and beneficial. This supports previous research identifying a need for additional post-treatment supports for individuals with oesophageal cancer. identified minimally important clinical differences of 1.40 for the HADS depression scale and 1.32 for the HADS anxiety. Differences between baseline and both immediate post-intervention and 3-month follow-up scores achieved these differences thus demonstrating the clinical importance of OptiMal for individuals with oesophageal cancer. Similarly, a change of 3.4 was identified as clinically important in the Euro QOL EQ-VAS. This difference was observed between baseline and the two follow-up data collection periods.The results of this study demonstrated statistically significant reduction in anxiety and depression three months following participation in OptiMal when compared to baseline scores. Puhan et al.19 Chen et al. reported lower scores on anxiety and depression subscales as measured by the HADS in oesophageal cancer survivors following completion of a rehabilitation programme addressing quality of life, sleep and well-being, but this did not reach statistical significance. Housman and colleagues suggested various reasons for psychological distress following oesophageal cancer diagnosis and treatment including the trauma of diagnosis, the intensity of oesophageal cancer treatment, risk of adverse outcomes or post-surgical complications, need to adjust to a new way of life following treatment and possible biological predispositions to conditions such as anxiety or depression. These range of difficulties support the need for post-treatment interventions to reduce the impact of psychological distress.Previous studies also reported significant decreases in anxiety and depression scores in oesophageal cancer survivors following completion of a nursing led rehabilitation intervention.12 Other studies have reported that increased confidence is a significant predictor of quality of life in individuals with oesphageal cancer.In this study, participants reported positive perceptions of OptiMal in relation to motivation, confidence, resilience and increased sense of agency over their health. They described greater understanding of their own health needs and increased confidence in managing their health after attending the six-week programme. This is an important finding as numerous studies reported that oesophageal cancer survivors may find establishing and maintaining agency over daily life challenging in the period following completion of cancer treatment and that individuals may defer important decision-making to ‘expert’ medical professionals. This is concerning given that anxiety and/or depression are linked to poorer health outcomes.42 However, the findings from the current study may yield some promising results for the impact of self-management interventions with regards to mood and well-being of oesophageal cancer survivors.Oncology teams are not always well equipped to meet the psychological or emotional support needs of oesophageal cancer survivors. It is interesting to note, however, that many studies examining interventions to support oesophageal cancer survivors do not examine changes in fatigue over time. The findings of this study indicated an improvement in participants’ fatigue with significant reductions in general and physical fatigue three months following completion of OptiMal. Study participants discussed how they used energy conservation strategies and had a greater understanding of the importance of prioritising self-care following the programme, which supported them in implementing fatigue management strategies. Zhang et al reported improved ability of oesophageal cancer survivors to engage in self-care activities, following an individualised nursing led rehabilitation programme. The current study sought to evaluate a group-based self-management programme. Therefore, in considering the combined findings of quantitative and qualitative analysis, OptiMal offers some initial promising results for future evaluations of fatigue management for oesophageal cancer survivors.Fatigue impacts on ability to participate in daily life activities, is common amongst oesophageal cancer survivors, and may persist for an extended period following completion of treatment. Existing literature shows that oesophageal cancer survivors may find establishing new routines challenging following oesophageal cancer surgery, and therefore the findings of this current study that participants experienced less difficulty with performance of usual activities over time is important and supports further evaluation of OptiMal for oesophageal cancer survivors. van Deudekom and colleagues recommended that approaches that focus on supporting participation in daily life activities could be useful to improve quality of life outcomes in oesophageal cancer survivors. HRQoL scores improved following completion of OptiMal, and remained at similar improved levels over time, but no statistically significant differences were identified. These findings are interesting and warrant further investigation in future studies with larger sample sizes. Other studies examining interventions to improve quality of life of oesophageal cancer survivors did not observe statistically significant improvements in global HRQoL, but did identify significant changes in domains of HRQoL, including pain, insomnia and financial difficulties. It is important to include robust measures of HRQoL in future studies examining outcomes of programmes to support oesophageal cancer survivors.In qualitative focus groups and follow-up interviews, participants discussed engaging in new or previously valued meaningful activities such as work and leisure following participation in OptiMal. These findings are important given that Larsen et al reported that oesophageal cancer treatment necessitated ‘putting life on hold’, and caused major disruption to daily activities, roles and routines.A sample size was not calculated for this study and there was a lack of a control group for the intervention which precludes analysis of the effectiveness of the OptiMal programme. The study sample was small, however, the study design incorporates a mixed methodology, with both quantitative and qualitative data to lend a rich insight into the outcomes and experiences of the programme participants. Three months follow-up interviews were completed with only three OptiMal participants. Additional interviews would lend greater insight into the longer-term experiences of participants upon completion of the OptiMal programme. is a specific measure of symptoms and emotional problems related to oesophageal cancer. However, in all other studies of OptiMal, the EQ-5D-3L was used to measure quality of life. Therefore, in order to maintain consistency with previous studies of OptiMal, the EQ-5D-3L was used in this study. However, in future studies, the EORTC Quality of Life Questionnaire – Oesophageal Cancer Module (EORTC QLQ-OES18) could be included as a validated measure of quality of life of individuals with oesophageal cancer.The EORTC Quality of Life Questionnaire-Oesophageal Cancer Module (EORTC QLQ-. OES18) Availability of self-management programmes for this population is limited at present, therefore, the findings of this study indicate promising outcomes for self-management interventions for this population. However, future research is required using robust, controlled study designs with a larger sample size in order to investigate the efficacy of OptiMal for oesophageal cancer survivors.The findings of this feasibility study indicate feasibility and acceptability of OptiMal for oesophageal cancer survivors. The content, format and delivery were reported as relevant and appropriate for individuals following completion of their cancer treatment and retention and adherence rates were high. Improvements in fatigue, participation in daily activities, anxiety and depression three- months following completion of OptiMal indicate potential effectiveness of this intervention. Previous studies examining the outcomes of OptiMal also identified increased frequency of activity participation, activity performance, satisfaction, self-efficacy, independence in daily activities and quality of life following participation.


The purpose of this study was to identify the clinical characteristics of patients with high-grade squamous intraepithelial lesions (HSIL) with abnormal endocervical curettage (ECC) and to evaluate the efficacy of abnormal preoperative ECC in predicting recurrence after a loop electrosurgical excision procedure (LEEP).We retrospectively analyzed a total of 210 cases of histological HSIL in female patients diagnosed using cervical biopsy and/or indiscriminating ECC, and these included 137 cases with normal ECC and 63 cases with abnormal ECC. We also collected preoperative information and data on postoperative human papillomavirus (HPV) and histological outcomes within 2 years.P < 0.001), predominantly menopausal (P = 0.001), had high-grade cytology (P = 0.032), a type 3 transformation zone (P = 0.046), and a higher proportion of HPV type 16/18 infection (P = 0.023). Moreover, age  and HPV 16/18 infection  were independent risk factors for abnormal ECC. With an observed residual lesion/recurrence rate of 9.5% over the 24-month follow-up, we noted a 9.3% higher rate in the abnormal ECC group when compared with the normal ECC group. Abnormal preoperative ECC  and positive HPV at the 12-month follow-up  were independent risk factors for residual disease/recurrence.The additional detection rate of HSIL using indiscriminating ECC was 5%. Patients with abnormal ECC were older (Preoperative ECC was one of the risk factors for post-LEEP residual/recurrent HSIL, and detecting abnormal ECC when managing older patients or patients with HPV 16/18 infection during colposcopy is critical. Cervical cancer ranks fourth among all malignant tumors in women in terms of the incidence and fatality rate, according to global cancer data, implying that effective prevention and treatment are critical . PersistEndocervical curettage (ECC) plays a significant role in evaluating lesions in the entire cervix and has an extensive range of clinical applications. The 2012 and 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines recommend endocervical curettage (ECC) for incompletely visible transformation areas, stating that ECC is also acceptable for visible lesions , 6. WhenAlthough ECC plays an important role in the preoperative diagnosis and postoperative follow-up of HSIL, it is still associated with various potential complications. Firstly, as a relatively invasive procedure in which the curette is inserted deep into the cervical canal, ECC is associated with pain and discomfort, which may lead to poor cooperation during the procedure. Secondly, inadequate sampling in the ECC procedure may cause the correct pathology to be missed. Furthermore, the population of women most likely to benefit from ECC has yet to be identified. Lastly, the relationship between preoperative ECC and post-LEEP recurrent/residual HSIL remains unclear.In this context, we designed this research to address the following two purposes: first, to identify characteristics of HSIL with abnormal preoperative ECC; and second, to evaluate the utility of abnormal preoperative ECC in predicting HSIL recurrence following LEEP.This was a retrospective study involving 358 women with histologically confirmed HSIL (ICD code 2E66.2) who underwent colposcopy-guided biopsy and ECC at the Renji Hospital between June 2018 and June 2019. We excluded women who did not consent to LEEP treatment, had post-LEEP invasive pathology, had positive margins on postoperative pathology, had missing data regarding preoperative general clinical information or postoperative follow-up data at 4–6 months, 12 months, and 24 months, and those who underwent hysterectomy within 24 months following LEEP. Finally, a total of 200 patients were included for analysis. This study was approved by the Ethics Committee of Ren Ji Hospital (reference KY2020-018). The consent was obtained the patient was informed the details about study design. For personal information protection, each patient was assigned a unique code for matching medical data. The data was de-identified and shared only among those involved in the trial.We evaluated the following clinical features: age, menstrual status (post-menopause/menstruation), anamnesis, type of transformation zone (TZ), cytology, and HPV status preoperatively and at 4–6, 12, and 24 months postoperatively. Anamnesis was divided into infection history, lesion history, and none/unknown, with infection history defined as persistent infection with high-risk HPV (HR-HPV) for more than 6 months prior to the histopathological diagnosis of HSIL, and no history of cervical lesions in the past; and lesion history was defined as a history of cervical lesions (including treatment history) with a histopathological diagnosis of squamous intraepithelial lesions (SILs) for more than 6 months prior to the preoperative colposcopy.Cytology results were reported per the Bethesda system: negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASCUS), Low-grade squamous intraepithelial lesions (LSIL), atypical glandular cells (AGC), HSIL, squamous cells cannot exclude high-grade squamous intraepithelial lesions (ASC-H). Further, they were classified as low-grade , and high-grade  .In accordance with WHO recommendations for cervical screening, HPV-DNA was used for HPV testing. The test was performed in department of docimology, and the 21 HPV genotyping kit diagnostic kit was from Hybribio Ltd., Hong Kong, which was based on PCR-low density gene microarray and inflow hybridization technology. According to “Global HPV DNA PP 2021 technical report” published by WHO, the accuracy of this kit is 100%. In this study, we focused only on high-risk HPV (HR-HPV). According to the results, classification of 21 types of HPV was listed here: high-risk HPV was defined as HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, and 68 , while low-risk HPV was defined as HPV types 6, 11, 42, 43, 44, and 81 . We classified the HPV status into three categories: HPV 16/18, other HR-HPV, and negative. One patient who had both HPV 16/18 and other HR-HPV types was included in the HPV 16/18 group.All tissue samples were sent to the pathology department for histological analysis, and all specimens were independently reviewed by two experienced pathologists with senior title. The lesions were diagnosed as HSIL or LSIL according to the 2014 classification criteria of the World Health Organization (WHO). LSIL: hyperplasia of squamous epithelial basal and parabasal-like cell, mildly disturbed nuclear polarity, mild anisotropy, few karyomitosis, lesion location was limited to 1/3 of subepithelial, and negative p16 staining or scattered dotted positivity in the epithelium. HSIL: chaos nuclear polarity, increased ratio of nuclear and plasma, increased nuclear karyomitosis, atypia cells extending over 1/3 of subepithelial layer or even the whole layer, and diffusing and continuous p16 staining distributing over field of 2/3 epithelial layer. Ectocervix and canal tissue samples were also collected during the colposcopy procedure. The outcomes following LEEP were classified into the following categories: (1) cure ; (2) residual disease ; and (3) recurrence  , 12, 13.Patients underwent a full evaluation consisting of an HPV test, a ThinPrep cytology test, colposcopy-guided biopsy, and ECC at 4–6 months postoperatively, and HPV and cytology screening were subsequently performed at 12 and 24 months following LEEP. Any patients with abnormal screening results underwent colposcopy-guided biopsy and ECC for further diagnosis at the histology level. The overall outcome of this study was residual/recurrent HSIL within 24 months following LEEP.N (%), and inter-group comparisons were done using the chi-square (χ2) test. A multivariate logistic regression model was used to analyze the risk factors for abnormal preoperative ECC and residual disease/recurrence within 24 months. A P-value of < 0.05 was considered statistically significant.The data were analyzed using IBM SPSS statistics software (version 19). Non-normal distribution measurement data were represented using P50 (P25–P75), and the non-parametric rank-sum test was used for inter-group comparisons. Enumeration data were expressed as The final analysis consisted of a total of 200 women patients. The mean age was 38 years (32.3–46), and a minority of them 17%) were post-menopausal. In the cytology evaluation, 37 patients (20%) were diagnosed as high-grade, 92 patients (46%) had HPV16/18 infection, and 97 patients (48.5%) had other HR-HPV infections. As for TZ, 89 patients (44.5%) had a type 3 TZ, and 78 (39%) patients had a type 1 TZ. 63 patients (31.5%) had abnormal preoperative ECC, and 137 (68.5%) had normal preoperative ECC . The post-menopausal rate of patients in the abnormal ECC group was 19.3% higher than that of normal ECC group patients . Compared with patients in the normal ECC group, those in the abnormal ECC group had a 7% higher HPV 16/18 infection rate and a 12.7% lower infection rate of other HR-HPV types . The proportion of patients with high-grade cytology in the abnormal ECC group was 13.6% higher than those in the normal group . The proportion of patients with type 3 TZ in the abnormal ECC group was 18.4% higher than that of patients in the normal group . There was no significant difference in the frequency of anamnesis between the two groups (P = 0.208).We compared the following clinical features between the normal ECC and abnormal ECC groups: age, menstruation, anamnesis, HPV, cytology, and TZ. As shown in Table P = 0.003). Compared with other HR-HPV alone, HPV 16/18  and negative HPV  were independent risk factors. Other clinical variables, such as menstruation, TZ, and cytology, could not be considered independent risk factors.In the multivariate logistic regression analysis, we took abnormal ECC as the dependent variable and included the following clinical characteristics that showed statistically significant differences in the univariate analysis: age, menstruation, TZ, cytology, and HPV Table . The resχ2 = 4.345, P = 0.037, RR = 2.409), which was shown in Fig. P = 0.654; 84.1% vs. 88.3%, P = 0.413, and 85.7% vs. 87.6%, P = 0.714, respectively).All the patients were followed up for 24 months, and the disease outcomes were evaluated Fig. . The oveP = 0.021), ECC (P = 0.043), and postoperative HPV at 6, 12, and 24 months . We further conducted a multivariate logistic regression analysis to filter the features with significant differences in the univariate analysis. The results indicated that abnormal preoperative ECC  and positive HPV at the 12-month follow-up  were independent risk factors for residual disease/recurrence , while there was no significant difference in the HR-HPV negative conversion rate at the three follow-up timepoints. This indicates that patients with abnormal preoperative ECC, even if the LEEP margin is negative, are at a higher risk of residual disease/recurrence, and this risk may not be related to postoperative HR-HPV infection. One probable explanation is that there can be skipped lesions deep in the cervical canal, and this area can be easily overlooked during HR-HPV sampling. It is not known if increasing the cone height can reduce the risk of residual disease/recurrence in women with HSIL and abnormal ECC without fertility requirements, and this needs to be explored in future studies. Second, in this study, the negative conversion rate of HR-HPV at 6, 12, and 24 months post-surgery was consistent with the rates previously reported , but the rate of negative conversion of HR-HPV did not increase progressively after 12 months post-operation –28.Some authors have noted that persistent HPV infection following LEEP may be related to the preoperative HPV viral load; however, in this paper, we focused on the HR-HPV type rather than viral load . As a reThis study has other limitations and deficiencies. Firstly, this study is a retrospective study, which has the inherent shortcomings of retrospective study, and further prospective multi-center study is needed. Thirdly, patients in this study were followed for only 24 months. We believe that adding additional follow-up time could yield more meaningful results.In conclusion, we found that women with HSIL and abnormal preoperative ECC were older, menopausal, had high-grade cytology, were infected with HPV 16/18, and had a type 3 TZ. Age and HPV 16/18 infection were independent risk factors for abnormal ECC. We suggest that preoperative ECC examination should focus on patients with the aforementioned characteristics since they may benefit more from it. Additionally, we found that abnormal preoperative ECC was one of the risk factors for post-LEEP residual/recurrent HSIL, with a 4.06 times higher risk of experiencing residual/recurrent disease. As a result, clinical attention to the detection of abnormal ECC can contribute to more focused management during follow-up.