Our study aimed to investigate the predictive value of intracranial pressure (ICP) and cerebral oxygen metabolism monitoring in the postoperative prognosis of patients with spontaneous intracerebral hemorrhage (SICH).2), and arterial partial pressure of carbon dioxide (PaCO2), were recorded after the operation. Further, the prognostic differences between the two groups were compared, and the predictive values were evaluated using the receiver operating characteristic curve (ROC) and area under the curve (AUC).The clinical data of 55 patients with SICH treated by neurosurgery were analyzed retrospectively. These patients were divided into two groups based on postoperative Glasgow Outcome Scale (GOS) scores, i.e., the poor prognosis group (GOS I-III) and the good prognosis group (GOS IV and V). Next, the ICP and cerebral oxygen metabolism indexes, such as brain temperature (BT), cerebral perfusion pressure (CPP), internal jugular venous oxygen saturation (SjvO2 in the good prognosis group were higher than those in the poor prognosis group. Moreover, the incidence of low PaCO2 in the poor prognosis group was higher than that in the good prognosis group.The results showed that the average ICP and BT in the good prognosis group were lower than those in the poor prognosis group. However, the CPP and SjvO2, and arterial PaCO2 may reflect the changes in brain function and cerebral blood flow, which are significantly correlated with the prognosis of patients. Further, our findings indicated that the combined postoperative ICP levels with cerebral oxygen metabolism indexes could guide clinical treatments and predict prognosis.Our results demonstrated that the average ICP, BT, CPP, SjvO Further, the study explored the role of ICP in combination with cerebral oxygen metabolism indexes to predict the prognosis of patients with SICH.Spontaneous intracerebral hemorrhage (SICH) is a cerebral hemorrhage caused by arterial rupture and is characterized by high morbidity, mortality and disability rate. The incidence of SICH in patients in Europe and the US is 9–28% whereas in China, it is 19–48% . AlthougThe clinical data of 55 patients with SICH, including 27 males and 28 females who underwent surgery at the Department of Neurosurgery of Shaanxi Provincial people’s Hospital from June 2020 to December 2021, were analyzed retrospectively. According to the guidelines [2 and arterial PaCO2 were monitored every 8 h. Further, the average ICP, BT, CPP (CPP = MAP-ICP), SjvO2, and arterial PaCO2 were calculated.All patients were transferred to the ICU after the operation and the head CT scan was reexamined within 12 h postoperatively. Moreover, the ICP, BT, and mean  arterial pressure (MAP) were collected per hour and SjvONo postoperative recurrent cerebral hemorrhage was observed in any patient. However, one patient died in the poor prognosis group, whereas no death or loss of mobility state was observed in the good prognosis group.When the postoperative ICP was higher than 22 mmHg and lasted for more than 15 min, dehydration drugs were administered intravenously, and analgesic and sedative drugs were also administered intravenously.When the postoperative ICP was higher than 30 mmHg, intermittent and rapid administration of multiple dehydration drugs, cerebrospinal fluid drainage, analgesic and sedative therapy, and hyperventilation therapy was implemented.When the postoperative ICP was higher than 45 mmHg, the head CT scan was reexamined and reoperation was considered according to the situation."Postoperative brain temperature management": the BT was controlled at 37℃. However, when the BT was above 37℃, an ice cap or ice blanket was used.Some specific treatments were administered as follows:2 value was obtained every 8 h. Meanwhile, arterial blood gas analysis was performed to obtain PaCO2.The ICP probe with BT monitor implanted into the ventricle of patients after the operation was removed after 3 days. The ICP and BT data stored on the intracranial pressure monitor were collected hourly, and the average value was calculated. The CPP obtained was the difference between the MAP and ICP. Besides, central venous catheterization was performed in patients, and the SjvOt-test was used to compare the measurement data following normal distribution, and the data were expressed in terms of mean ± standard deviation. The Mann_Whitney U test was used to analyze the non-normal distribution of measurement data between groups, and the data were expressed using median (M) and quartile (IQR). Moreover, the classified variables were expressed by the number of cases and percentage or constituent ratio. The chi-square and Fisher’s exact probability tests were used for comparison. A P_value < 0.05 was considered statistically significant. The MedCalc software (version 19.0.2) was used to prepare the subject receiver operating characteristic curve (ROC), and the area under the ROC curve (AUC) was calculated to evaluate the significance of each index in predicting the prognosis of patients.SPSS 22.0 software was used for statistical analysis. A Student’s n = 31) and the poor prognosis group (n = 24). However, the average ICP and BT in the good prognosis group  were significantly lower than those in the poor prognosis group . The CPP and SjvO2 of the good prognosis group  were higher than those of the poor prognosis group , with a statistically significant difference. The incidence of low PaCO2 in the poor prognosis group was significantly higher than that in the good prognosis group , as shown in Table No significant difference in age, sex, and GCS score was observed between the good prognosis group n = 3 and the P < 0.001), BT , CPP , SjvO2  and low PaCO2 . The results revealed that the combination of ICP levels with cerebral oxygen metabolic indexes is of significant importance for predicting poor prognosis in patients with SICH, as shown in Table To analyze the significance of different indexes on the poor prognosis of patients with SICH after operation, the average values of indexes were compared which were as follows: ICP  [SICH can cause a series of pathophysiological changes that are usually characterized by the rapid expansion of hematoma in the brain parenchyma, which extends to the ventricular system and subarachnoid space or dural space and leads to a high risk of recurrent cerebral hemorrhage, serious vascular events, epilepsy, dementia, and other neurological complications . Acute hry (TBI) . Our stuSecondary brain injury caused by increased ICP levels is one of the main causes of poor prognosis in patients with SICH. High ICP levels increase the inhomogeneity of capillary permeability, which causes disorders of cerebral microcirculation, blood shunt, and suboptimal transport of energy substrates. The average ICP levels can indicate the occurrence and development of secondary damage and predict the optimal time point for intervention , which iBT is closely related to brain metabolism and the intracranial environment. An increase in BT may reflect the fluctuation in brain metabolism, hyperemia, or local inflammation. The increase in temperature leads to an increase in cerebral blood perfusion. This high cerebral blood volume may increase ICP . Thus, a2 monitoring is a technique for estimating the overall balance between brain oxygen supply and metabolic needs. Nearly 80% of brain tissue reflux venous blood flows rapidly to the jugular bulb through the venous sinus with little extracerebral venous blood mixing [2 value is between 55 ~ 75%. A value less than 55% indicates that the patient has insufficient CBF owing to various reasons  or increased metabolic oxygen demand (CMRO2). A value greater than 75% signifies hyperemia, reduced metabolic requirements of the brain , and microvascular shunts caused by disturbance of oxygen extraction and diffusion in the damaged brain tissue. These secondary lesions lead to poor neurological prognosis. Thus, SjvO2 monitoring helps determine the balance between CBF and CMRO2, monitor insufficient or excessive cerebral perfusion, and guide the treatment and prevention of secondary brain injury [The artificial hyperventilation is used after craniocerebral surgery in addition to dehydration and diuresis to reduce ICP through cerebral vasoconstriction and cerebral perfusion. However, inappropriate hyperventilation can lead to a significant decrease in CBF and an imbalance between cerebral oxygen supply and demand, resulting in neurological complications and increased mortality and disability rates . Therefod mixing . Normalln injury .2. Hypocapnia (PaCO2 < 35 mmHg) may be a common and neglected cause of brain hypoxia after SICH, which is related to poor neurological prognosis and delayed cerebral ischemia [2 lead to the imbalance of blood flow-metabolism, resulting in the transition to anaerobic metabolism or leading to cerebral ischemia, especially in the brain tissue with pre-existing CBF damage. Therefore, cerebrospinal fluid alkalosis can lead to neurotoxicity, especially through the production of excitatory amino acids, such as N-methyl-d-aspartic acid, which have severe cell cytotoxicity [CBF is primarily regulated by arterial PaCOischemia . Hypocapischemia . Hypocaptoxicity . This suCraniotomy is the main surgical method for the treatment of SICH and the hematoma can be removed thoroughly. Although some shortcomings of craniotomy should be paid attention, including severe trauma, obvious brain tissue injury, high blood loss, long operation time, severe brain edema reaction, many complications, poor prognosis and curative effect . SICH coThe prognosis of patients with SICH is often poor and challenging. Our study assessed a variety of monitoring methods which are used to reflect different pathophysiological conditions in postoperative patients with SICH and explored their predictive values. It was suggested that the average ICP indicated intracranial space-occupying which guided dehydration and surgical treatment. Similarly, BT and CPP suggested hemodynamic changes, guided treatments and predicted prognosis. Moreover, the levels of SjvO2 and arterial PaCO2 suggested the changes of cerebral oxygen metabolism and CBF. Further, ROC curve determined that combined postopertaive ICP levels with cerebral oxygen metabolism indexes such as CPP, BT, SjvO2 and arterial PaCO2 could guide the clinical intervention and predict the prognosis of patients with SICH more effectively.


To determine to what extent head and neck cancer (HNC) survivors participate in health behaviors (HBs) recommended by the National Cancer Center Network (NCCN®).Participants identified through the tumor registries at the Abramson Cancer Center (ACC), University of Pennsylvania and affiliated sites. Eligibility: (a) diagnosis and treatment HNC; (b) aged 18 to 70 years; (c) ≥ 1-year post-diagnosis; (d) human papillomavirus (HPV) status confirmed; (e) ability to understand written English. Potential participants received an explanation of the study, informed consent, self-reported questionnaire, and self-addressed stamped envelope.451 individuals eligible, 102 (23%) agreed to participate, HPV positive (74%). Current smoking rare (7%), historical use common (48%). Current alcohol use common (65%), average 2.1 drinks/day, 12 days/month. 22% binge drank with an average of 3.5 binge-drinking sessions per month. Nutritional behavior mean 7.1 (range 0–16), lower scores indicating better nutrition. Body mass index (BMI) 59% overweight/obese. Adequate aerobic exercise 59%, adequate strength and flexibility 64%. Leisure time activity, 18% sedentary, 19% moderately active, 64% active. All participants reported having a primary care physician, 92% seen in the previous 12 months.Most HNC survivors participated in some HBs. Current smoking rarely reported, binge drinking and high BMI most common negative HBs. Opportunities remain to improve dietary and exercise behaviors.The NCCN® has outlined HBs that decrease likelihood of cancer survivors developing comorbidities that could impact overall survival. It is incumbent on healthcare providers to educate and encourage cancer survivors to participate in these HBs. HNC accounts for almost 4% of cancers in the United States (U.S.) and 3% worldwide , 2. SubsThe impact of dental health on survival in HNC is greater for oropharynx cancer patients compared to other sites in the head and neck, and in contrast to previous studies, this was independent of education and income . WhetherWhile the rate of non-HPV related HNC is decreasing due to decreased smoking prevalence, the incidence of HPV related cancers is increasing at a rate of approximately 2.5% per year , and HPVThe prognosis for oropharynx cancer is dependent on four factors: HPV status, pack years of tobacco smoking, tumor stage, and nodal stage . HPV-relRecent evidence suggests HPV infection increases the risk of other oral cancers, including tongue, palate, and floor of the mouth . AlthougSeveral HBs are problematic for HNC patients. More than a quarter screen positive for problem drinking or alcoholism at diagnosis –22. BetwData also suggests that HNC patients have multiple HB deficits, including poor intake of fruits and vegetables . In addiLittle is known about post-treatment HBs among HPV associated HNC survivors, including the prevalence of tobacco and alcohol use in patients with HPV associated HNC. There are also a number of HBs, such as dental care, diet, and adherence to cancer and non-cancer surveillance recommendations for which little is known for HNC survivors regardless of HPV status. This is of particular importance since HNC comorbidities  are likely to be at least partly moderated by HBs of these individuals.The goal of this study was to describe modifiable determinates of HBs and illness perceptions among HNC survivors to inform interventions to improve long-term outcomes. Moreover, we recognized that these HBs and perceptions might differ according to HPV status and other factors which have been shown to influence HBs among cancer survivors.The primary objective of this study was to describe the range of HBs relevant to both recurrence and survivorship among HNC survivors and determine whether these differ by HPV status and demographics. In addition, measures of illness QoL and distress among HNC survivors were included to determine whether these differ by HPV status and demographics.Lastly, assessment of the relationship between illness perception, QoL, distress, and HB among HNC survivors was classified by HPV genotype status to determine if population stratification is necessary in intervention design.Potential participants were identified and screened by our research personnel through the tumor registry at the Abramson Cancer Center (ACC) of the University of Pennsylvania as well as affiliated sites  to allow for broader reach. Potential participants were eligible if they: (a) had a diagnosis and at least partial treatment of HNC as reported in the registry; (b) were between 18 and 70 years of age; (c) were more than 1-year post-diagnosis; (d) had a recorded confirmation of HPV status; and e) could understand written English.Potential participants were contacted via mail with an opt out option. Those who did not opt out were contacted by phone or email and asked to participate in a study. If potential participants were unavailable by telephone after two attempts, staff contacted them by mail. Potential participants received an explanation of the study, informed consent documentation, a self-reported questionnaire, and a self-addressed stamped envelope for return of materials. Individuals not returning the materials within the first three weeks received up to two additional phones calls to encourage completion and return of the study materials. This process was repeated on an ongoing, weekly basis. Once data were received, they were entered into a secured database.A few specific instruments make up the self-reported questionnaire.Demographic and Medical Variables – All participants responded to standard demographic questionnaires assessing age, ethnic/racial identification, marital status, number of offspring, educational level, income, insurance status, living situation, and presence of chronic medical comorbidities.Health Behaviors – HBs included items recommended by Glasgow et al. assessing aerobic activity, strength-flexibility, leisure time activity, smoking, alcohol consumption, and access to a physician . This baIllness Perceptions – The Illness Perception Questionnaire-Revised (IPQ-R)  was usedPsychological Distress – We assessed cancer-specific distress using the Impact of Event scale (IES) , which hQuality of Life – We assessed QoL in two ways. The University of Washington QoL Questionnaire (UW-QOL)  is a briMedical record abstraction included patient demographics, primary treatment, tumor site, and HPV status.Analysis was restricted to enrolled patients who returned surveys.A total of 905 individuals were initially screened for eligibility. Of these, 451 were eligible and approached. A total of 102 (23%) patients participated in the study, and usable data were collected from 93 participants. Table As can be seen in Table Describe the range of HBs relevant to both recurrence and survivorship among HNC survivors and determine whether these differ by HPV status and demographics.p < 0.05). There was no relationship between current alcohol use status, days drinking per month, or number of drinks on average per drinking session and either HPV status or gender.Smoking and Alcohol use. Although current smoking was rare (7%), historical use of tobacco was common (48%). Current alcohol use was also common (65%). Among those who reported alcohol use, there was an average of 12 days per month in which alcohol was consumed, though this ranged from 1 to 30 days. On those days in which alcohol was consumed participants reported an average of 2.1 drinks per day. Binge drinking (consuming > 5 drinks in one sitting) was reported by 22% of those who drank, with an average of 3.5 binge drinking sessions per month among those reporting any binge drinking. There was no relationship between HPV and smoking status. Women were more likely than men, however, to be current smokers (Diet and Weight. Scores on Starting the Conversation—Diet (SCT-Diet), our measure of nutritional behavior can range from 0 to 16 with lower scores indicating better nutrition. Overall, the sample mean was 7.1 (SD = 2.4) with scores ranging from 0 to 13. BMI was calculated from self-reported height and weight. Forty-one percent of the overall sample were Normal or Underweight, while 59% were overweight or obese.p < 0.01), and were more likely to be obese (p < 0.05).There was no relationship between HPV status or gender with respect to nutritional behavior. Men had a higher BMI (M = 27.3) than women , although there was no difference with respect to HPV status for aerobic activity or leisure time activity status. Men were more likely than women to report adequate aerobic activity (p < 0.01), though there was no gender difference for strength and flexibility or leisure time activity status.Physical Activity. With respect to the overall sample, 59% reported adequate aerobic exercise and 64% adequate strength and flexibility on the RAPA. With respect to leisure time activity, 18% would be classified as sedentary, 19% as moderately active, and 64% as active. Individuals with HPV positive status were marginally more likely to meet criteria for adequate strength and flexibility than those with negative status .Quality of Life. Table p < 0.001) than the normative value of 71 found among a large sample of similar patients. Similarly, Social Functioning was high  and significantly higher than the normative value of 74 (p < 0.01). There were no significant differences between groups based on HPV status. Males reported significantly higher Physical  and Social Functioning  compared to females.With respect to the HNC cancer specific UW-QOL measure, composite scores reflecting Physical and Social Functioning were computed. Scores can range from 0 to 100 with higher values reflecting better QoL. Physical Functioning was high  and significantly higher (p < 0.01) Avoidance  and overall cancer-specific distress  compared to males.Cancer Specific Distress. Scores on the IES were computed for Intrusion and Avoidance subscales as well as the overall composite which was then used to categorize level of distress. Table Describe illness perceptions underlying cancer and non-cancer future events and determine whether these differ by HPV status and demographics.The IPQ-R assesses the common sense model illness perceptions: Identity (symptoms associated with the disorder), timeline , consequences (the anticipated outcome of the disorder), and treatment and personal controllability (what can be done to control the threat posed by the disorder and by whom), illness coherence , and emotional representation (negative affective reactions to the illness). Higher scores in the dimensions including identity, timeline, consequences, and emotional representation reflect more strongly held beliefs about the number of symptoms attributed to the illness, the chronicity of the condition, the negative consequences of the illness, and negative emotional reactions to the illness. High scores on the personal control, treatment control and coherence dimensions, represent positive beliefs about the controllability of the illness and a personal understanding of the condition. See Table p < 0.05). No other differences were noted between HPV status groups. There were no significant differences between groups as a function of gender.With respect to HPV status, individuals with non-HPV related HNC reported significantly stronger beliefs in the chronicity of their condition than individuals with HPV related disease  previously established a symptom grading tool for patients who receive treatment for cancer, tracking the severity (grade) of symptoms. The EORTC is now developing a QoL tool investigating health behaviors as well as physical, psychological, and social aspects of HRQOL to further capture the impact of treatment on the cancer survivor . This inOsazuwa-Peters et al.  reportedNo significant reports of depressed mood or suicidal ideation were identified in trial participants. HPV-related cancer has improved long-term survival compared to HPV non-related cancer. Improved surgical and radiation techniques have more recently led to the potential for fewer and/or less severe long-term toxicities and improved QoL. Further study is needed regarding if and how these issues impact the suicide rate.Web based resources are a potential source of support for patients and their families before, during and after treatment for HNC. Fang et al.,  reportedThe participants provided information regarding a wide range of physical, psychological, and general well-being issues impacted by their cancer in this trial. After completion of treatment, a portion of survivors in this study continued to participate in behaviors that place them at risk for additional cancers. These results provide insight into areas of focus for potential future educational issues aimed at patients undergoing treatment for HNC.+ HNC population. [A limitation of this study is the small number of non-HPV + participants. This is the result of the study being conducted primarily in an urban academic center as well as the fact that the HPV + HNC is outpacing non-HPV HNC diagnoses. Potential future studies could focus on the participation of multiple centers to capture a more heterogeneous population. Although the results of this study are not generalizable to all HNC patients, they are generalizable to the growing HPVulation. , 62.HBs that are important for cancer survivors have been identified by the NCCN. Most participants in this study participated is some of the recommended HBs after completing their cancer treatment. Regrettably, several HNC survivors continued to participate in risky behaviors, placing them at risk for recurrence and/or other cancers. Future research should include educational interventions during treatment as well as during survivorship to provide a better understanding of the importance of following the recommended HBs to maintain optimal health and well-being.


Background: In the United States, the human papillomavirus (HPV) vaccine is approved for use in individuals up to age 45. Individuals 15 years and older require three doses of the vaccine to complete the recommended dosing series. Incomplete HPV vaccination rates  among those over age 26, however, remain high. This study examined the independent effects of individual- and neighborhood-level factors on incomplete HPV vaccination rates in the United States (U.S.) among those aged 27–45 years. Methods: This retrospective cohort study used administrative data from Optum’s de-identified Clinformatics® Data Mart Database to identify individuals aged 27–45 years who received one or more doses of HPV vaccine between July 2019 and June 2022. Multilevel multivariable logistic regression models were applied to the data on 7662 individuals identified as being fully or partially vaccinated against HPV, nested within 3839 neighborhoods across the U.S. Results: Approximately half of the patients in this study (52.93%) were not completely vaccinated against HPV. After adjusting for all other covariates in the final model, being older than 30 years old decreased the odds of not completing the HPV vaccine series. Participants living in South-region neighborhoods of the U.S. had enhanced odds of not completing the vaccine series compared with those residing in Northeast-region neighborhoods . There was significant clustering of incomplete HPV vaccination rates at the neighborhood level. Conclusions: This study revealed that individual- and neighborhood-level factors were associated with the risk of not completing the HPV vaccine series among individuals aged 27–45 years in the U.S. Interventions to improve HPV vaccination series completion rates for this age group should take into consideration both individual and contextual factors. Although the United States (U.S.) witnessed a tremendous reduction in the incidence of human papillomavirus (HPV)-associated cancers between 2006 and 2018 after the introduction of the HPV vaccine, the burden of HPV-associated cancers remains elevated .Evidence from large observational and randomized-controlled trial (RCT) studies has shown that the available HPV vaccines reduced cervical cancer incidence by 90% in fully vaccinated girls and young adults ,5,6,7. HDue to unsatisfactory rates of HPV vaccination in the U.S., the National Vaccine Advisory Committee (NVAC) was charged by the U.S. Department of Health and Human Services (HHS) to examine the factors responsible for low HPV vaccination uptake and provide recommendations on how to bolster the effectiveness of nation-wide efforts to improve HPV vaccination uptake and coverage rates .Several studies ,17,18,19Few studies have examined the effects of contextual- or area-level factors on individuals who initiated and completed the HPV vaccination series, leaving out individuals who started their HPV vaccine series but did not complete it ,19. The The overarching aim of this research work was to determine whether individual- and neighborhood-level factors were predictors of incomplete HPV vaccination among individuals aged 27–45 in the U.S. in a single analytical framework with a view to providing up-to-date, accurate, and credible data to inform the design of programs and interventions to address the high rate of incomplete HPV vaccine series.This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (S1 STROBE checklist).® Data Mart Database, which is mainly used for research. The database included data on insurance claims for vaccinations, medical services rendered, and prescriptions by United Health Group, Inc., a private health insurance company in the United States. The participants were mostly adult professional employees, with a slightly higher representation of southern states. The data on claims for medical services were obtained from medical tables, while demographic and enrollment information was obtained from member tables. Enrollment data were used to determine the continuity of medical coverage and to confirm an enrollee’s healthcare. Our study used secondary data with anonymized information that fulfilled all federal regulations and guidelines, which are clearly set out under the 45 Code of Federal Regulations (CFR) 46 regarding its use for research activities involving human subjects.We conducted this retrospective cohort study using health insurance claims from Optum’s de-identified ClinformaticsWe obtained 158,636 records for participants who had a claim for HPV vaccines identified by the Current Procedural Terminology (CPT) codes 90649, 90650, and 90651. All study participants were continuously enrolled for at least 12 months before the start of the vaccine series and at least 12 months after. Twelve months of enrollment after the first HPV vaccine dose was chosen to ensure a long enough time for an enrollee to complete the vaccine series. Individuals with no HPV vaccination history were excluded from the analysis. We restricted our sample to individuals aged 27 to 45 years old who received at least one dose of the HPV vaccine. After applying all the exclusion criteria above, we selected participants who had complete sex and age data, and this resulted in 7662 participants in the study sample  because it was limited to the use of previously collected anonymized data.This study analyzed de-identified datasets collected between 2019 and 2022 by Optum’s de-identified ClinformaticsIn this study, we considered the following individual-level factors: sex, age, smoking status, and obesity. Sex was categorized as female and male. The age of participants was categorized as 27–30, 31–40, and 41–45. For smoking, we used 1 year before and 1 year after claims data and at least 1 inpatient claim or 2 other non-drug claims of any service type with diagnosis (DX) codes or 1 common healthcare procedure coding system (HCPCS) code claim of any type. DX codes used included the following: ‘F17200’, ‘F17201’, ‘F17203’, ‘F17208’, ‘F17209’, ‘F17210’, ‘F17211’, ‘F17213’, ‘F17218’, ‘F17219’, ‘F17220’, ‘F17221’, ‘F17223’, ‘F17228’, ‘F17229’, ‘F17290’, ‘F17291’, ‘F17293’, ‘F17298’, ‘F17299’, ‘O99330’, ‘O99331’, ‘O99332’, ‘O99333’, ‘O99334’, ‘O99335’, ‘T65211A’, ‘T65212A’, ‘T65213A’, ‘T65214A’, ‘T65221A’, ‘T65222A’, ‘T65223A’, ‘T65224A’, ‘T65291A’, ‘T65292A’, ‘T65293A’, ‘T65294A’, and ‘Z720’. HCPCS codes: ‘99406’, ‘99407’, ‘G9276’, and ‘G9458’. The Charlson comorbidity index was categorized as none, one, and two or more. Smoking status was coded as non-smoker and smoker. For obesity, we used the previous year’s claims data. The DX code of E66 was used to identify obesity.The percentage of high school graduates and median household income in the patient’s primary ZIP code was obtained from the U.S. Census Bureau database American Community Survey (ACS) 5-year estimates from 2020. This was a record linked to health insurance claims data from Optum’s de-identified Clinformatics Data Mart database using ZIP code (aggregate data) as the unique identifier. The percentage of high school graduates was categorized as ≤88.2, 88.2 to 93.1, 93.1 to 95.9, and ≥95.9. Neighborhood household income was categorized as ≤USD 58,782, USD 58,782 to USD 76,288.5, USD 76,288.5 to USD 97,944, and ≥USD 97,944. We used the term “neighborhood” to describe clustering within the same geographical living environment. Neighborhoods were based on sharing a common ZIP code area.The outcome of interest was incomplete HPV vaccination, defined as receiving one or two doses out of the recommended three doses of the HPV vaccine for this age group.Descriptive analysis for this study involved the use of numbers and percentage for all categorical variables to show the distribution of the outcome variable by the independent variables.We specified a two-level multilevel model for 7662 participants (level 1) nested within 3839 neighborhoods (level 2). We constructed four models. The first model was a null model that had no determinant variables and was specified to disintegrate the quantity of variation that existed at the neighborhood level. The second model adjusted for only individual-level variables, while the third model adjusted for neighborhood-level factors. The fourth model controlled for all the covariates simultaneously. A mixed-effect logistic regression model was utilized to test the association between the predictors and outcome variables.The results of fixed effects (measures of association) were shown as adjusted odds ratios (aORs) with their 95% credible interval (CrI).The intra-cluster correlation (ICC), variance partition coefficient (VPC), and median odds ratio (MOR) were used to perform a random effects analysis. MOR is the median value of the odds ratio between a cluster with the highest likelihood of an outcome and another with the lowest likelihood of an outcome; it measures the cluster variance as OR.p-value of <0.05 was used to define statistical significance for all measures of association assessed.Goodness-of-fit of the models was assessed with the Bayesian deviance information criterion (DIC), and all models were well-fitted. Multicollinearity among the different independent variables was checked with the variance inflation factor (VIF). All multivariable mixed-effects modeling was performed using multilevel windows (MLwiN) software, version 3.06 , callingThe analysis involved 7662 participants who received one or more doses of the HPV vaccine (level 1) nested within 3839 neighborhoods (level 2) across the U.S. More than half of these patients had incomplete HPV vaccination rates see . About 6p < 0.0001) across neighborhoods from the null model , odel see . The ICCResults of the MOR also confirmed evidence of neighborhood contextual phenomenon modifying odds of incomplete HPV vaccination. The MOR for incomplete HPV vaccination was 1.24 in the null model; this relatively moderate MOR suggests that the clustering effect was moderate. The neighborhood-level heterogeneity in odds of incomplete HPV vaccination decreased to a MOR of 1.21 when both individual- and neighborhood-level factors were controlled for in the final model. Thus, there are moderate variations between neighborhoods in the predisposition for not completing the HPV vaccine series.This research work examined individual- and neighborhood-level factors as determinants of incomplete HPV vaccine series in the population studied using claims data by one of the largest private insurance companies in the U.S. This study confirms the importance of neighborhood-level variations with respect to incomplete HPV vaccine series among adults 27–45 years of age who initiated the vaccine in the U.S. In particular, the study showed that the context and region of the neighborhood in which people reside are linked to incomplete HPV vaccine series even after taking into consideration the individual-level sociodemographic risk factors.Findings from this study show that older participants were less likely not to complete their vaccination series compared to younger participants, which is contrary to findings of previous studies ,25,26 caThe effects of neighborhood-level factors on incomplete HPV vaccination status are highlighted in this study. Our findings indicate that the likelihood of not being fully vaccinated against HPV is higher for residents in neighborhoods in the South region compared with those living in neighborhoods in the Northeast. This could be due to the high rate of vaccine hesitancy among the people living in the South ,31. RuraApproximately half of the participants in this study did not complete their vaccination series, which is consistent with the findings of previous studies ,36,37 onPrevious studies ,36 have Another reason people may refuse to initiate and complete their HPV vaccination series could be due to logistical reasons. Participants of a cross-sectional study that examined this topic stated that the distance to the vaccination centers was too far for them and that they did not have time due to the pressure of work to go to the vaccination centers to initiate as well as complete their vaccine series . A betteFuture studies should be conducted to examine the effects of the numerous unexplored/under-explored cluster-level risk factors associated with incomplete HPV vaccination, which this current study could not investigate.® Data Mart Database included only privately insured participants, and these results are not generalizable to publicly insured individuals.Findings from this study should be interpreted in the context of its limitations. One limitation of this study, as with most retrospective cohort studies, is the use of existing data, which provided us with limited data for us to adjust for more risk factors, such as race/ethnicity, marital status, and socioeconomic or other demographic factors. This may result in residual confounding. Second, information on our covariate of smoking and obesity came from diagnosis codes and relied on insurance claims for outpatient and hospitalization services, which are not always 100% accurate or complete. Third, we were unable to determine whether our study participants may have been partially or fully vaccinated through the second insurance provider. Fourth, we did not adjust for rural/urban residency, preventive behaviors, and healthcare services usage. Lastly, Optum’s de-identified ClinformaticsDespite the limitations of this study, it has several strengths that are worth mentioning. One important strength of this current study is the use of a large national database of privately insured enrollees. The database contains longitudinal tracking at the individual patient level, which provides at least one year of follow-up data. This will make the findings of the study to be relevant to the study population and generalizable if applied to similar populations. In addition, being a population-based study with a large sample size is an important strength of this study. Furthermore, no studies to our knowledge have looked at factors associated with HPV vaccine series completion in the catch-up age range of 27–45 years old. Lastly, the use of a mixed-effects analysis for this study revealed other contextual-level factors aside from the individual-level factors that were responsible for the variations in incomplete HPV vaccination, which a standard single-level regression model would not be able to reveal.This study revealed that individual- and neighborhood-level factors are significantly associated with failure to complete the HPV vaccine series among adults who previously received one or two doses. Both individual- and contextual-level characteristics should be taken into consideration during the design, planning, and implementation of policies, programs, and interventions aimed at improving the completion of the HPV vaccine series among adults in the U.S.


Cervical cancer, primarily driven by Human Papillomavirus (HPV) infection, stands as a substantial global health challenge. The TP53 gene’s, Arg72Pro polymorphism has emerged as a noteworthy player in cervical cancer development, particularly among individuals harboring high-risk (HR) HPV types. Additionally, long non-coding RNAs (lncRNAs), exemplified by metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), exert critical roles in cancer biology. This study delves into unravelling the intricate connections linking HPV infection, TP53 Arg72Pro polymorphism, and MALAT1 expression in the context of cervical cancer.Within a cohort of cervical cancer patients, we discerned HPV infection statuses, executed genotyping for the TP53 Arg72Pro polymorphism, and quantified MALAT1 expression through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Statistical analyses meticulously probed relationships intertwining HPV infection, TP53 polymorphism, and MALAT1 expression.Our investigation revealed a striking prevalence of the TP53 Arg72Pro polymorphism among HPV-positive subjects, accompanied by a robust and statistically significant correlation linking MALAT1 overexpression (p<0.01) and HR-HPV positivity (p<0.03). Importantly, a subset of MALAT1 overexpression cases unveiled a concomitant TP53 Pro72Pro polymorphism. In contrast, HPV-negative invasive cervical carcinoma samples exhibited no discernible shifts in MALAT1 expression.The contours of our findings sketch a compelling landscape wherein HR-HPV infection, TP53 polymorphism, and MALAT1 expression intertwine significantly in cervical cancer. The voyage ahead entails delving deeper into molecular underpinnings to decipher MALAT1’s nuanced role and its dance with TP53 within HPV-associated cervical carcinogenesis. This expedition promises insights that may engender targeted therapeutic interventions and bespoke prognostic markers, tailored to the realm of HR-HPV-related cervical cancer. Cervical cancer remains a formidable global health challenge , driven Moreover, the emerging landscape of long non-coding RNAs (lncRNAs) in cancer biology introduces further layers of complexity. Among these, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an infrequently spliced lncRNA, has surfaced as a significant player within various gynecological malignancies . DysreguIn this study, our objective was to meticulously scrutinize the potential interplay among HPV infection, the TP53 Arg72Pro polymorphism, and the lncRNA MALAT1 expression.A total of 200 women within the reproductive age range (18–65 years) were enrolled in this study between April 14, 2019, and December 14, 2019. Among these, 150 women constituted the target group testing positive for high-risk HPV types (16/18/31/33/35), while the remaining 50 women comprised the control group, testing negative for HPV. Cervical cancer screening involved liquid-based cytology using Hologic Inc.’s system  for both groups, with details of HPV status and cytology results previously published and presented in Given the inherent stability of human nucleic acids in liquid-based cytology media , TP53 geFor TP53 Arg72Pro polymorphism determination, PCR-RFLP and BstUI restriction endonuclease  were employed. Amplification of a targeted 296-base pair (bp) fragment utilized the following primers:Forward: 5’–TTGCCGTCCCAAGCAATGGATGA– 3’Reverse: 5’–TCTGGGAAGGGACAGAAGATGAC– 3’.Each 50 μL PCR reaction contained 0.1 μg genomic DNA; 1 U Taq DNA polymerase; 10 pmol of each primer; 200 mM of each deoxynucleotide triphosphate (dNTP); 1.5 mM magnesium chloride (MaCl2), with primers and reagents procured from Norgen Biotek Inc., . The PCR conditions comprised an initial 5 min denaturation at 95°C, 30 cycles of 30 sec at 95°C, 30 sec at 57°C, and 1 min at 72°C, followed by a final step at 72°C for 7 min. Subsequent BstUI digestion of the resulting 312-bp PCR products of TP53 exon 4 adhered to the manufacturer’s guidelines . After separation via 4% agarose gel electrophoresis with ethidium bromide, digestion products were visualized using an ultraviolet (UV) transilluminator.Reverse transcription of lncRNA MALAT1 RNA involved the high-capacity RNA-to-cDNA kit  in a 20 μL reaction volume, with inclusion of a negative control in each experiment to verify absence of genomic DNA contamination. All cDNA samples were stored at −20°C until further molecular analysis. The MALAT1 primers were:Forward: 5′-CCCCACAAGCAACTTCTCTG-3′,Reverse: 5′-TCCAAGCTACTGGCTGCATC-3′.®. The qRT-PCR protocol encompassed an initial cycle at 95°C for 2 min, followed by 45 cycles of amplification at 95°C for 10 sec, 60°C for 10 sec, and 72°C for 10 sec. The melting curve analysis introduced a rapid cooling cycle to 40°C for 30 sec, with real-time fluorescence acquisition at the elongation step (72°C). Subsequent melting curve analysis incorporated steps at 55°C for 20 sec, 95°C for 20 sec, ramping at 0.19°C/sec, with continuous acquisition mode and the final step at 40°C for 10 sec. The reference gene, beta-2-microglobulin (B2M) was included, utilizing validated qRT-PCR assays [Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) measured MALAT1 expression in a 10 μL reaction containing 1 μL of cDNA, 2 μL of PCR Synthesis Buffer, 1 μL of MgCl2, 0.2 μL of dNTPs, 0.5 μL of BSA, 0.1 μL of Hot Start DNA polymerase, 0.3 μL of forward and reverse primers, and 1 μL of 1X LC GreenR assays . StandarR assays , with thStatistical analysis employed SPSS v.28.0.1.1 software, with intra-group comparisons determining p-values; significance was established at p<0.05. Ethical clearance was secured from the Bioethics International Committee of the Petre Shotadze Tbilisi Medical Academy . All procedures adhered to the Helsinki Declaration of 1975, revised in 2013, with participants receiving comprehensive study information and providing written informed consent prior to inclusion.This study sought to elucidate potential connections among HR-HPV infection, the TP53 Arg72Pro polymorphism, and lncRNA MALAT1 expression. Through TP53 Arg72Pro polymorphism analysis, we identified three distinct variants:Homozygous wild-type Arg/Arg variant, characterized by bands of 259 bp and 53 bp.Homozygous Pro/Pro variant, evident as a single band of 312 bp.Heterozygous variant, signified by the presence of all three bands .Among HPV-positive subjects, the TP53 gene codon 72 polymorphism was identified in 142 cases (94.7%). Within this group, 102 individuals (68.0%) were identified as Pro/Pro homozygotes, and 40 individuals (26.7%) exhibited Arg/Pro heterozygosity. Detailed information on HPV status, liquid-based cytology results, and TP53 Arg72Pro polymorphism can be found in Among the HPV-positive samples, 66.7% (100 out of 150) exhibited MALAT1 overexpression. Notably, only 15% of these cases were associated with TP53 Arg72Pro polymorphism, implying that a significant majority, 85%, of MALAT1 overexpression instances are linked to TP53 Pro72Pro polymorphism . ConversOur study aimed to unravel the intricate interplay between HPV infection, the TP53 Arg72Pro polymorphism, and the expression of the long non-coding RNA (lncRNA) MALAT1, particularly within the context of cervical dysplasia progression. MALAT1, a molecule of intense investigation across various cancers, including lung, endometrial, breast, and invasieve cervical cancer, initially surfaced as a potential as a prognostic marker for non-small cell lung cancer metastasis . Its subOur findings underscore the TP53 Arg72Pro polymorphism’s prevalence among HPV-positive subjects, with 94.7% harboring this variant, comprising 68.0% Pro/Pro homozygotes and 26.7% Arg/Pro heterozygotes. Intriguingly, our analysis of MALAT1 overexpression and HPV status unveils 66.7% of HPV-positive samples exhibit heightened MALAT1 expression. Of note, a significant 85% of cases with MALAT1overexpression are associated with TP53 Pro72Pro polymorphism. In contrast, a smaller fraction (15%) of HPV-positive cases with MALAT1 overexpression exhibited TP53 Arg72Pro polymorphism. This pattern is concordant with previous observations and suggest a robust connection between HPV infection, TP53 polymorphism and MALAT1 overexpression, particularly in cervical tissues of experiencing escalating dysplasia. We posit that the TP53 Pro72Pro polymorphism potentially fosters p53 inactivation, unleashing uncontrolled MALAT1 transcription–a potential keystone culminating in transformation and cancerogenesis upon HR-HPV infection. However, the intricate molecular underpinnings driving MALAT1 dysregulation within HPV-related cervical carcinogenesis warrant nuanced exploration. Deciphering these mechanisms stand to illuminate pathogenic insights and unveil promising therapeutic avenues for both HPV-associated cervical cancer and its premalignant stages.Our study sheds light on the intricate relationship between HPV infection, the TP53 Arg72Pro polymorphism, and the heightened expression of the long non-coding RNA (lncRNA) MALAT1 in cervical tissues with associated dysplasia. Extensively explored in various cancers MALAT1’s propensity for fostering hyperproliferation and metastasisis noteworthy. Notably, our findings reveal a predominance of TP53 Pro72Pro polymorphism among HPV-positive subjects, correlated with increased MALAT1 expression. This hints at a plausible role of TP53 Pro72Pro polymorphism in unhindered MALAT1 transcription upon HPV infection, potentially fueling cervical carcinogenesis. While our study furnishes valuable insights into the intricate interplay between HPV infection, TP53 polymorphism, and MALAT1 overexpression, unravelling the molecular tapestry underlying these connections beckons further exploration. The enigmatic MALAT1 dysregulation within HPV-related cervical carcinogenesis merits in-depth investigation, offering a potential avenue for identifying therapeutic targets tailored to HPV-associated cervical cancer.S1 Checklist(DOCX)Click here for additional data file.


Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) among HPV-positive women undergoing colposcopy at the Second Xiangya Hospital of Central South University, Hunan, China. Additionally, we aimed to assess the impact of C. trachomatis or M. genitalium co-infection with HPV on the severity of cervical lesions.The aim of this study was to determine the prevalence of C. trachomatis and M. genitalium. Multivariate logistic regression analyses were performed to examine the association between sexually transmitted pathogens and cervical lesions.We collected HPV data, cervical cytology results, and demographic information from 439 women attending colposcopy. Cervical swabs were obtained for simultaneous amplification testing (SAT) of C. trachomatis was detected in 17 (3.87%) individuals, and M. genitalium in 16 (3.64%) individuals. There was no co-infection of C. trachomatis and M. genitalium. The highest prevalence of M. genitalium was observed in women aged 19–30 years , with a subsequent decline in prevalence with increasing age (Ptrend = 0.014). The most common HPV subtype in our study was HPV52 (30.79%), followed by HPV16 (18.62%), HPV58 (16.95%), and HPV53 (10.02%). Infection with HPV16 , HPV31 , and HPV33  was associated with an increased severity of cervical lesions, while HPV53 infection was not likely to lead to advanced cervical lesions . The leukocyte level in vaginal secretions (P = 0.042) and cervical cytology results (P < 0.001) showed associations with the degree of cervical lesions. However, there was no significant association between C. trachomatis or M. genitalium infection and the severity of cervical lesions, nor with their co-infection with HPV16.Among the participants, Chlamydia trachomatis or Mycoplasma genitalium and the degree of cervical lesions in HPV-positive population in Hunan, China. Our findings emphasized the need to pay more attention to M. genitalium infection among young women. Increased levels of leukocytes in vaginal secretions may be linked to cervical lesions. HPV16, HPV31, and HPV33 in Hunan province, China, may exhibit higher cervical pathogenicity.There was no correlation between co-infection of  In early 2021, the GLOBOCAN 2020 database, produced by the International Agency for Research on Cancer (IARC), revealed that cervical cancer (CC) ranks as the fourth most common cancer worldwide among women in terms of both incidence and mortality . While tChlamydia trachomatis (CT) is the most common causative agent of bacterial sexually transmitted infections (STIs) and can result in various complications in women, including pelvic inflammatory disease (PID), hydrosalpinx, and infertility [C. trachomatis infection and HPV infection, indicating they are mutual risk factors [C. trachomatis infection rates between HPV-infected and non-HPV-infected groups or between groups with different cervical biopsy results [C. trachomatis infection and high-risk HPV infection [C. trachomatis and HPV infection remains controversial and requires further investigation. Additionally, most existing studies focus solely on the relationship between C. trachomatis infection and HPV infection, disregarding the fact that HPV infection does not necessarily lead to cervical lesions [C. trachomatis infection and cervical lesions directly reflects the impact of C. trachomatis on female cervical health, yet few relevant studies have been conducted.Sexually transmitted pathogens pose a significant public health concern worldwide, particularly for women’s health. ertility . Some st factors , 8. Howe results . Similarnfection . Therefo lesions . TherefoMycoplasma genitalium (MG) is an emerging sexually transmitted pathogen that causes genitourinary tract diseases and has recently gained attention [M. genitalium can cause cervicitis [M. genitalium infections are asymptomatic. The increasing prevalence and antimicrobial resistance of M. genitalium are concerning [M. genitalium is not commonly conducted in most hospitals in China, and epidemiological data on M. genitalium in Hunan Province is lacking. The relationship between M. genitalium, HPV progression, and cervical lesions remains unknown but is of significant importance.ttention . Researcrvicitis  and is arvicitis  and infervicitis . Furtherncerning . HoweverC. trachomatis infection and HPV infection. Moreover, epidemiological data on M. genitalium and its correlation with HPV infection are limited. Therefore, we conducted a study among HPV-positive individuals who underwent colposcopy in Hunan Province, China. This study aimed to investigate the distribution of HPV subtypes, as well as the prevalence and age distribution of C. trachomatis and M. genitalium. Additionally, it analyzed the risk factors for cervical lesions and examined the influence of co-infection with C. trachomatis or M. genitalium on cervical lesions in HPV-infected individuals. These findings have important implications for the prevention and control of infections caused by these pathogens, as well as the management of cervical lesions.Currently, there is inconsistency in the association between Trichomonas vaginalis (TV) at the time of examination, (2) women had sexual activity or gynecological examinations within the past 24 h, (3) women who are menstruating, (4) pregnant women, (5) women who had vaginal douching or used vaginal medications within the past 48 h, (6) women who had undergone hysterectomy, (7) women who had undergone cervical loop electrosurgical excision procedure (LEEP), laser treatment, or cold knife conization (CKC) within the past year, and (8) women with incomplete laboratory measurements. Following the application of these criteria, a total of 439 women (aged 19 to 74 years) were included in the final analysis. The study protocol was approved by the institutional review board of the Second Xiangya Hospital of Central South University  and by the Chinese medical research registration information system (Ref number: MR-43-23-027426). Written informed consent was ensured from all study participants to take part in the study voluntarily after they get informed about the objective and purpose of the study.A cross-sectional study was carried out at the Second Xiangya Hospital of Central South University from July to September 2022. A population of 500 women visiting the hospital’s gynecology department and undergoing colposcopy was invited to participate in the study. The inclusion criteria were as follows: (1) women with a history of sexual activity, (2) positive HPV test results, and (3) informed consent. The exclusion criteria included: (1) women infected with bacterial vaginosis (BV), fungi, or C. trachomatis and M. genitalium. The cervical swab was then placed into 2 ml of a transport and preservation medium  and immediately frozen at -80℃. Acetic acid and Lugol iodine were applied to examine the cervix and vaginal walls. Any suspicious areas were biopsied for histopathological assessment. The histopathological grading included no squamous intraepithelial lesions (NO SIL), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cervical cancer. If multiple biopsy samples were taken simultaneously, the sample with the highest grade was considered for analysis. The researchers will track and record the biopsy results of each patient in the hospital’s medical record system using the patient’s unique card number.The study participants underwent colposcopy performed by a single trained gynecologist. After inserting a vaginal dilator to fully expose the cervix, a flocked swab  was inserted into the cervix and rotated several times to collect cervical secretions for the detection of Before undergoing colposcopy, the patient’s laboratory measurements, including HPV types, cervical cytology tests, and the level of vaginal leukocytes, as well as demographic information such as age, pregnancy history, reproductive history, and menopause, were recorded.Laboratory examination data were collected when the subjects underwent colposcopy.HPV testing was performed using the Human Papillomavirus nucleic acid typing test kit , which allowed for the detection of 21 HPV types. Among these, 15 HPV types were classified as high-risk HPV , and 6 HPV types were classified as low-risk HPV .The pathologists categorized the results of the cervical cytology as follows: Negative for intraepithelial lesion or malignancy (NILM), Atypical squamous cells of undetermined significance (ASC-US), Atypical squamous cells: cannot exclude high-grade squamous intraepithelial lesion (ASC-H), Low-grade squamous intraepithelial lesion (LSIL), High-grade squamous intraepithelial lesion (HSIL), Atypical glandular cells (AGC) and Squamous cell carcinoma (SCC). None of the patients participating in this study had been diagnosed with AGC. Therefore, the AGC cytological grade is not listed in Table The levels of leukocytes in the vaginal secretions of the participants were examined by gynecologists. Based on the number of leukocytes observed in each high-power field, the examination results were classified into three categories: 0–15/HP, 16–30/HP, and > 30/HP.All laboratory measurements were obtained from the Second Xiangya Hospital, Central South University.C. trachomatis and M. genitalium commercial test kits . The magnetic beads containing the target nucleic acid were mixed with the prepared amplification detection liquid. A 30µL magnetic bead suspension was placed into each microreaction tube, and 10µL of preheated enzyme solution was added to start the reaction. The reaction process was set at 42℃ for 1 min per cycle, with a total of 40 cycles. The fluorescence signals in the fluorescein FAM channel were recorded every minute. A Ct value of ≤ 35 indicated a positive result for C. trachomatis RNA or M. genitalium RNA. For samples with Ct values between 35 and 40, retesting was required. A Ct value of < 40 in the retesting was considered positive.In a biosafety cabinet, the swab soaked in the preservation solution was fully ground and then discarded. The same volume of normal saline was added and thoroughly mixed. The target RNA was extracted using magnetic beads by adding nucleic acid extraction solution to the appropriate samples, following the instructions provided by the C. trachomatis and M. genitalium by age. A multivariate logistic regression model was employed to evaluate factors associated with cervical lesions using variables with a P-value of less than 0.1 in univariate analyses. Throughout the study, results were considered statistically significant when P ≤ 0.05.All statistical analyses were conducted using SPSS version 25.0 . The Shapiro-Wilk test was employed to assess the normal distribution of variables. Continuous variables that were not normally distributed are presented as the Median , while categorical variables are presented as percentages. The Chi-square test or nonparametric Kruskal-Wallis test was used to compare the three groups statistically. Chi-square trend tests were used to examine changes in the prevalence of . The median age of the participants was 45 years (IQR 36–53). Based on cervical biopsy results, the 439 HPV-positive patients were categorized into three groups: no squamous intraepithelial lesions group , low-grade squamous intraepithelial lesion (LSIL) group (n = 127), and high-grade squamous intraepithelial lesion (≥ HSIL) group (n = 108). Table C. trachomatis was detected in 17 individuals (3.87%), M. genitalium in 16 individuals (3.64%), and there was no co-infection of C. trachomatis and M. genitalium. Significant differences were observed in the leukocyte level of vaginal secretions among the groups (P = 0.042), with the highest leukocyte level (> 30/HP) observed in the HSIL group (12.38%). Cervical cytology results also showed significant differences among the groups (P < 0.001), with the NILM grade being more common in the group without complicated lesions (81.86%), while the ASC-H (10.19%) and HSIL (15.74%) grades were more common in the HSIL group. No significant differences were found in age, pregnancy history, reproductive history, menopause, HPV single or mixed infection, or the positive rate of C. trachomatis or M. genitalium among the groups.According to the inclusion and exclusion criteria, a total of 439 out of the 500 individuals who underwent colposcopy were included in our study Fig. . The medroup n = 27, and hC. trachomatis and M. genitalium with respect to age. The overall prevalence of M. genitalium was 3.64% , with statistically significant differences observed among different age groups. The highest prevalence was found in women aged 19–30 years , and it steadily decreased as women aged, reaching 1.94%  in women over 50 years old  and in women over 50 years old , and it did not show a trend with increasing age (Ptrend = 0.301).Subjects in our study were stratified by age (ranging from 19 to 74 years), and we examined the changes in the prevalence of C. trachomatis or M. genitalium and the severity of cervical lesions (Table ). The results showed that neither LSIL nor HSIL phenotypes were associated with either C. trachomatis or M. genitalium in any of the models, using the NO SIL phenotype as the reference. After adjusting for all confounding factors, the prevalence of C. trachomatis or M. genitalium was not found to be associated with the severity of cervical lesions .Multivariate logistic regression analyses were conducted to investigate the association between ns Table . The resOut of the 439 women included in our study, 20 had untyped HPV test results, so we analyzed accurate HPV typing results for 419 women. The most prevalent HPV genotype was HPV52 in 129 subjects (30.79%), followed by HPV16 in 78 subjects (18.62%), HPV58 in 71 subjects (16.95%), and HPV53 in 42 subjects (10.02%). In the univariate analysis, HPV genotypes associated with cervical lesions were HPV16 , HPV31 , and HPV33 , indicating that they increased the severity of cervical lesions. Surprisingly, patients infected with HPV53 were less likely to develop advanced cervical lesions , we further explored the combined effects of sexually transmitted infections (STIs) and HPV genotypes on the severity of cervical lesions. Due to the small number of positive cases of C. trachomatis and M. genitalium, and the fact that none of the patients infected with HPV31 and HPV33 were infected with C. trachomatis or M. genitalium, we only investigated the relationship between HPV16 or HPV53 and C. trachomatis or M. genitalium . Since patients infected with HPV53 rarely had C. trachomatis infection, and co-infection was only present in the NO SIL group but not in the LSIL and HSIL groups, statistical analysis could not be performed. Furthermore, no significant interaction was found between HPV53 and M. genitalium (P > 0.05).Having identified the correlation between HPV16, HPV31, HPV33, and HPV53 with the extent of cervical lesions Table , we furtC. trachomatis and M. genitalium infections, as well as the impact of co-infection with HPV on cervical lesions. The aim of the study was to contribute to the existing research in this field. C. trachomatis was detected in 17 participants (3.87%), while M. genitalium was detected in 16 participants (3.64%). Co-infection of C. trachomatis and M. genitalium was not observed. The prevalence of M. genitalium was highest in women aged 19–30 years  and decreased steadily with age (Ptrend = 0.014). It was observed that HPV16, HPV31, and HPV33 may exhibit higher cervical pathogenicity in Hunan province, China. Additionally, a surprising finding was the association between elevated levels of leukocytes in vaginal secretions and cervical lesions. However, neither C. trachomatis nor M. genitalium infection, alone or in co-infection with HPV16, were found to be associated with the severity of cervical lesions. This study provided insights into the pathogenicity of different HPV subtypes on cervical lesions and explored the age distribution of M. genitalium and its relationship with cervical lesions in the HPV-positive population in Hunan province, China. These findings are expected to contribute to the understanding of the epidemic pathology of sexually transmitted pathogens and aid in the prevention, screening, and control of such pathogens.A cross-sectional study was conducted among 439 HPV-positive women who underwent colposcopy in Hunan province, China, to investigate the prevalence and age distribution of C. trachomatis or M. genitalium.The population included in our study had certain unique characteristics. Samples were collected from the colposcopy laboratory, and patients who underwent colposcopy were excluded if they had bacterial vaginitis, fungal vaginitis, trichomonas vaginitis, HIV, or syphilis. This exclusion was done to prevent worsening of the patients’ condition and to avoid the risk of infection for healthcare workers. Therefore, bacterial, fungal, trichomonas, HIV, and syphilis infections were not considered in our study population to eliminate any potential synergistic pathogenic effects they might have with C. trachomatis and M. genitalium was relatively low, with C. trachomatis often having a higher prevalence compared to M. genitalium. For instance, among the general female population visiting gynecology departments in Sichuan province, China, the infection rates of C. trachomatis and M. genitalium were reported as 6.5% and 2.6%, respectively [C. trachomatis and M. genitalium were 11.3% and 1.0%, respectively [C. trachomatis (3.87%) was slightly lower than that reported in other studies, while the infection rate of M. genitalium (3.64%) was slightly higher. Co-infection of M. genitalium with other sexually transmitted pathogens has been reported. In young high-risk women with asymptomatic bacterial vaginosis in the United States, the prevalence of M. genitalium co-infection with C. trachomatis was 29.9%, and co-infection with Neisseria gonorrhoeae was 23.6% [M. genitalium with C. trachomatis was only 0.6%, and with N. gonorrhoeae was 0.1% [C. trachomatis and M. genitalium was not observed, likely due to differences in the study population and the low positive rates of C. trachomatis and M. genitalium.The prevalence of both ectively . In a stectively . In our as 23.6% . Howeverwas 0.1% . In our M. genitalium was observed in women aged 19 to 30 years , and this prevalence declined steadily with age, consistent with previous research [C. trachomatis was higher among women over 50 years old , but not in young women under 30 years of age. This finding contradicts Chen’s research, as Chen et al. discovered that the prevalence of C. trachomatis infection was highest among the group aged ≤ 25 years and gradually decreased with age [C. trachomatis infection was higher in the group aged > 35 years compared to the group aged ≤ 35 years [C. trachomatis is not necessarily exclusive to young women. The inconsistent results may be attributed to differences in study areas and populations. In conclusion, our findings suggest that the growing openness towards sexual concepts and the younger age at first sexual intercourse among Chinese women may increase the likelihood of sexually transmitted pathogen infections in young women, but the health of elderly women should not be disregarded.Studies have indicated that sexually transmitted pathogen infections are more prevalent among young women . Our sturesearch , 17. HowC. trachomatis or M. genitalium were more likely to have elevated leukocyte levels in vaginal secretions [Few studies have explored the relationship between leukocyte levels in vaginal secretions and the severity of cervical lesions. A study conducted in southwest China found that patients infected with cretions . In our cretions , 20. Somcretions , 22. In Persistent infection with high-risk HPV can result in cervical lesions and potentially cervical cancer. The prevalence and distribution of HPV subtypes vary across countries, races, and populations. In our study, the most prevalent HPV genotype was HPV52 (30.79%), followed by HPV16 18.62%), HPV58 (16.95%), and HPV53 (10.02%). These results align with data from other Chinese populations. A study conducted in southern China identified HPV52, HPV16, and HPV58 as the three most common HPV subtypes .62%, HPV. This inC. trachomatis and M. genitalium infection, either alone or in co-infection with HPV16, and the severity of cervical lesions. Regarding C. trachomatis infection, its association with HPV infection and cervical lesions is currently controversial. Several studies have indicated an association between C. trachomatis infection and HPV infection as well as cervical lesions [C. trachomatis infection does not increase the risk of HPV infection and cervical lesions [M. genitalium infection, there is limited research on its association with HPV infection and cervical lesions. A study by A et al. found no association between M. genitalium infection and HPV infection or cervical lesions [Many previous studies have primarily focused on the relationship between cervical cytology results and sexually transmitted pathogens , 24. How lesions , 23. How lesions , 10, 25, lesions , which iC. trachomatis and M. genitalium, the number of positive cases was insufficient to conduct comprehensive stratified analysis. Additionally, the samples collected were primarily from Changsha city, Hunan Province, which may affect the generalizability of the findings regarding the prevalence of sexually transmitted pathogens. Future research should be conducted using large longitudinal cohorts, including women from different locations, to identify and validate risk factors for HPV infection and the progression of cervical lesions, ultimately aiming to prevent cervical cancer.This study had several limitations. Firstly, it was a cross-sectional study, which cannot accurately capture the dynamic changes in HPV infection and cervical lesions among the subjects. Secondly, the sample size was small, and due to the low infection rates of M. genitalium infection among young women, while C. trachomatis infection in older women should not be overlooked. Increased levels of leukocytes in vaginal secretions may be associated with cervical lesions. In Hunan province of China, HPV16, HPV31, and HPV33 appear to have higher pathogenicity in relation to cervical lesions. The findings of this study highlight the ongoing controversy regarding whether C. trachomatis and M. genitalium infection, either alone or in co-infection with HPV, contribute to an increased severity of cervical lesions. Further clarification is needed through large longitudinal cohort studies in the future.In conclusion, our study suggests that greater attention should be given to


The response to chemotherapy was evaluated after three months in patients with the HPV-16 lineage. Results: HPV DNA was detected in 104 (88.1%) of the 118 patients. HPV-16 was present in 63 patients (53%). Lineages of HPV-16 were identified in 57 patients and comprised 33 instances of (57.8%) lineage A, 2 instances of lineage B (3.5%), 2 instances of lineage C (3.5%), and 20 instances of (35.0%) lineage D. The median age of the patients was 48.4 years (range 25–85 years). Squamous cell carcinoma was detected 48 times (84.2%). Adenocarcinoma was more likely to occur in lineage D, as three of the four cases occurred in this lineage. A total of 11 patients with the HPV-16 variant were treated with chemoradiotherapy. After three months, it was observed that nine of the eleven patients (81.8%) achieved a complete response, five with the lineage A type, two with the lineage C type, and two with the lineage D type. The two cases of partial response and disease progression, one of each, occurred in lineage A. Conclusions: In addition to the small number of patients and HPV variants, we noticed a better response in patients with the HPV-16 lineage A. Increasing the sample size could be helpful to better assess the impact of HPV variants on cervical cancer treatment.Background: HPV is strongly related to cervical cancer. HPV lineages can contribute to a response to cervical cancer therapy. The aim of this research was to estimate the frequency of human papillomavirus (HPV)-16 lineages in specimens of cervical cancer, relate the pathological factors in these variants, and assess their response to treatment with radical chemoradiotherapy. Methods: Samples of cervical cancer were collected from women who were referred to a reference cancer hospital to test the presence of human papillomavirus-type DNA. The standard protocol of this service consisted of cisplatin-based chemotherapy of 40 mg/m There were an estimated 8.6 million new cases of cancer and 4.2 million deaths among women in 2018. Cervical cancer occupies the fourth position in incidence and mortality, with 569,847 new cases (6.6%) and 311,365 deaths (7.5%). Its frequency relates to the Human Development Index (HDI), and although its frequency is declining in developed countries, we have observed a burden of new cases in less developed regions. There are expected to be 710,249 new cases in the world as soon as 2030 [Human papillomavirus (HPV) is a non-enveloped virus, measuring 55 nm, whose genome is composed of DNA in a circular double-stranded format. The viral particle, or virion, consists of an outer layer or capsid that surrounds the viral genome. The viral capsid is not surrounded by a lipid membrane, has icosahedral symmetry, and consists of 360 copies (arranged as 72 pentamers) of the major capsid protein L1 and 12 molecules for the minor capsid protein L2 [Persistent HPV infection is directly related to the appearance of premalignant lesions and the development of cervical cancer. It is a necessary condition but is not sufficient, as its association with other factors is necessary for the development, maintenance, and progression of intraepithelial lesions .Cervical HPV infection is quite common. It is estimated that 80% of women are infected by the age of 50. About 90% of these infections are naturally eliminated by the body’s immune system within one year .High-risk human papillomavirus (HPV) infection is supposed to be the main cause of cervical carcinoma . Its preIn addition to the classification of HPV types, this infection can also be analyzed in terms of variants. A variant lineage must show a difference between 1% and 10% in the nucleotide sequences of the protein L1. Since 2013, the classification of HPV-16 variants has utilized a numerical alpha pattern and are now grouped into four main strains: A, B, C, and D. Lineage A includes the sublineages that were previously known as European  and Asian (A4). Lineage B comprises the sublineages African 1a and African 1b . Lineage C encompasses the old African 2. Lineage D includes the North American (D1) and Asian American  sublineages . SeveralThe process that leads a cell infected by HPV to transform into a malignant lesion is a slow process, which is associated with the oncogenic type, the viral load, the affected site, and the persistence of the infection. Low-grade intraepithelial lesions are usually observed in productive viral infections. The progression of these lesions to malignancy is often associated with the active transcription of the viral genes E6 and E7, which promote cell growth and contribute to the immortalization of these cells, with the integration of the viral DNA through the host cell DNA ,16.Regarding treatment options, hysterectomy approaches include simple hysterectomy (type A), modified radical hysterectomy (type B), and radical hysterectomy (type C)—the latter being recommended for the treatment of cervical cancer . It is aThe role of genotyping HPV to determine a better outcome in cervical cancer treatment remains controversial. Some studies have proposed that the determination of the HPV type has no prognostic consequence in cervical cancer , and othDue to the importance of this topic on public and women’s health, the present study aimed to determine the prevalence of HPV and investigate the relationship between HPV-16 strains and their response to treatment with chemotherapy, radiotherapy, and brachytherapy in patients with cervical cancer.Patients with proven cervical carcinoma were requested to join this study, which was conducted between April 2016 and April 2018 at the Aldenora Bello Cancer Hospital and Tarquinio Lopes Filho Cancer Hospital, located in São Luis, Maranhão (Brazil). Samples of tumor material were collected from 125 women with cervical cancer. A follow-up was carried out, and the oncological treatment was recorded, according to the protocols of the hospitals, when the patients returned for a consultation to evaluate the treatment performed.This study was approved by the Institutional Ethical Committee under the number 1.289.419/2015. All patients were informed and given signed permission to participate before the trial’s initiation.Patients referred for outpatient care at the gynecological oncologist services at these hospitals were invited to participate in this study. If they accepted the objectives of the study, they signed an informed consent form (ICF) and were given a questionnaire for the collection of socio-demographic data.The patients in whom the presence of a tumor was demonstrated in a biopsy of the uterine cervix and who met the inclusion criteria were followed up after diagnosis. Treatment data were collected via a clinical questionnaire, which recorded the performed oncological procedures  until their first follow-up return with tests to assess their response to the treatment performed. The inclusion criteria were women over 18 years of age diagnosed with cervical cancer who agreed to participate in this research by signing an informed consent form.The exclusion criteria were women with small lesions in which the performance of a biopsy could interfere with staging, women undergoing psychiatric treatment, and women who refused to sign the informed consent form. The collected samples containing tumor fragments were placed in microtubes containing 1 ml of RNAlater and were transported in thermal boxes at 4 °C and sent to the Multiuser Laboratory located in the Biobank of Tumors and DNA of Maranhão following registration and storage protocols. After 24 h, the sample of RNA was removed and stored in a freezer at −80 °C until the procedures were performed in the laboratory.The extraction of genomic DNA from frozen samples was performed as per the protocol described by the DNeasy Blood and Tissue Kit user manual .For the identification of HPV DNA in samples of cervical tumors, the PCR nested amplification technique was used, according to Vidal et al. (2016) . The determination of HPV genotypes was performed via the automated sequencing of the PCR product using the MegaBACE 1000 sequencer . Reactions were carried out at the Molecular Biology Laboratory of the State University of Maranhão, located at the Center for Higher Studies in Caxias (CESC—UEMA). The sequencing was performed using the BigDye™ Terminator v3.1 Cycle Sequencing Kit , according to the manufacturer’s protocol. For the analysis and alignment of the nucleotide sequences obtained in the sequencing, the Chromas program was used, which obtained the electropherograms of the HPV DNA sequences present in the samples. For the confirmation and identification of the type of HPV, a comparison of the nucleotide sequences of these samples was performed, and the samples were then sequenced and then submitted to the world nucleotide database GenBank using the BLAST program (NCBI).After identifying the types of HPV present, the samples infected by HPV-16 were submitted to a new PCR amplification protocol of regions to the viral genome, which was capable of identifying the variant to which that type of HPV detected belonged.Two pairs of primers were used, which amplified the entire LCR region and the E6 gene.www.megasoftware.net, accessed on 20 September 2018). An analysis of the variants of HPV-16 and the construction of the phylogenetic tree was carried out at the National Institute of Cancer under the supervision of Dr. Miguel Angelo Martins Moreira.The PCR product was further purified and sequenced according to the aforementioned protocol. Consensus sequences were joined using the software Geneious version 2020.1 (Biomatters Ltd.), and all generated sequences were aligned according to the specific strains of HPV-16, using reference sequences proposed by Burk et al. (2013)  and usinThe staging system of the International Federation of Gynecology and Oncology (FIGO) was used to classify all patients. Contrast-enhanced computed tomography (CT) of the abdomen and pelvis was performed to assess lymph node involvement. Pathological features, such as tumor size, histological type, the grade of differentiation, hemoglobin levels, and parametrial and vaginal features, were recorded. We included patients treated with concurrent chemotherapy radiotherapy treatment (CCRT) for the purpose of identifying a cure.2 for 6 cycles weekly, with concurrent external radiation. Intracavitary brachytherapy was provided, employing a high-dose-rate (HDR) after the loading technique, which was supplied in four fractions, two times a week, with doses of 7–7.5 Gy per session to Point “A”, according to the clinical stage and tumor volume.Patients were treated according to the department protocol. The external beam radiotherapy (EBRT) was performed with a 4-field box procedure to the whole pelvis, protecting organs at risk, with prescript 45–50.4 Gy doses, daily fractions of 1.8 Gy, and five weekly fractions. An additional parametrial boost up to 54 Gy, protecting the midline, was provided with a dose planned according to the stage. External beam irradiation was executed using a Cobalt-60 or 6 MV linear accelerator (Siemens). The patients under CCRT treatment received cisplatin, 40 mg/mThe assessment of the local response to treatment was programmed to occur 12 weeks after the end of radiation, performed through a gynecological clinical examination and cervical cytology, as well as CT in all cases (with a necessary ultrasound or magnetic resonance imaging whenever needed) and cervical biopsies in uncertain cases, in order to assess the absence or presence of a tumor. They were classified as a complete response , partial response , stable disease , and the progression of disease .This study complied with all the principles set out in the Declaration of Helsinki and Resolution 466 from December 2012 of the National Health Council of the Ministry of Health, guaranteeing the secrecy, reliability, and dignity of the subjects in the research, as well as guaranteeing their autonomy and the defense of their vulnerability.The study project was approved by the Research Ethics Committee of the Federal University of Maranhão (CEP-UFMA) under Consolidated Opinion No. 1.289.419/2015.2 (squared) test was used, and p-values of ≤ 0.05 were considered statistically significant. Descriptive statistical analysis was performed using the Stata program (version 14.0), with data presented in the form of figures and tables. To evaluate the association between the HPV and sociodemographic and clinical variables, the χThe values referring to “does not know/did not answer” were excluded from the association analysis.The study population consisted of 118 women who were diagnosed with cervical cancer and treated at the Aldenora Bello Cancer Hospital and Tarquínio Cancer Hospital Lopes Filho. The age range varied between 25 and 89 years, with an average age at diagnosis of 50.6 years old. Most of the cases, around 75 (63.5%), occurred between 30 and 59 years of age. Most women declared themselves to be Brown (69.5%). Women who were married or in a stable union predominated (51.7%) Smoking was a habit reported by about 50 women (42.4%). The largest contingent of women were illiterate (33.0%), and only 22 women (18.6%) had 12 or more years of education. The per capita income in the families of 76 women (64.4%) was less than half the minimum wage (corresponding to an amount of BRL 880.00 at the time of the study). Most of the women, 52 (44.1%), came from municipalities with a low human development index (HDI).When evaluating the patients’ reproductive histories, it was observed that 75 women (63.6%) started sexual activity before the age of 18, and 63 women (53.4%) reported having up to two sexual partners throughout their lifetime. High parity was observed, with 62 women (52.6%) having more than five children. Most women, 87 (73.7%), reported having knowledge of birth control; 15 women (12.7%) reported not using birth control, while 48 women (40.7%) had used it regularly or irregularly over the last 3 years .There was a high frequency of advanced stages at diagnosis. EC IIB was recorded in 30 women (25.4%) and EC IIIB in 50 women (42.4%). Squamous cell carcinoma was the most frequent, with 94 cases (79.7%), while adenocarcinoma was observed in 11 cases (9.3%). About 67 patients (56.8%) had a tumor with a diameter greater than 4.0 cm. The presence of lymph node metastasis was observed in 12.7% of cases .Regarding the treatment performed, it was observed that surgery (either followed or not by an adjuvant with radiotherapy and/or chemotherapy) was the procedure performed on 25 women (21.1%), most of whom were in their initial clinical stage. Treatment with radiotherapy and chemotherapy, alone or in combination, was used for 64 women (54.2%), most of whom were in advanced clinical stages. A total of six patients (5.0%) underwent treatment in another city, and about twenty women (16.9%) did not undergo treatment.The HPV test was positive in 104 samples (88.1%). About ninety-eight samples were of oncogenic high-risk HPV , four samples were low-risk HPV (HPV-09 and HPV-53), and co-infection was observed in two samples. HPV-16, with sixty-three samples (53.3%), was the most prevalent, followed by HPV-18 with twelve samples (10.2%), HPV-35 with six samples (5.1%), HPV-45 with five samples (4.2%), HPV-52 with four samples (3.4%), HPV-9 with three samples (2.5%), HPV-33 with three samples (2.5%), HPV-31 with two samples (1.7%), HPV-58 with two samples (1.7%), and HPV-53 and HPV-59 with one sample (0.8%) each.Squamous cell carcinoma was observed in 53 samples (84.1%) of HPV-16 and in 8 samples (66.7%) of HPV 18. Proportionally, adenocarcinoma was more frequent in HPV-18, where it occurred in three samples (25%), compared to HPV-16, where it was recorded in four samples (6.3%).From a total of 63 samples for HPV-16, in 6 samples, it was not possible to identify the intratype variant, leaving 57 samples in which the variant was identified—33 samples (57.8%) of the A lineage, 2 samples (3.5%) from lineage B, 2 samples (3.5%) from lineage C, and 20 samples (35.0%) from lineage D.Regarding age, the average was 48.3 years for the A lineage, 58.5 for the B lineage, 58.5 for the C lineage, and 46.4 for the D lineage. Squamous cell carcinoma was detected in forty-eight samples (84.2%), followed by adenocarcinoma in four samples (7.0%), of which three belonged to the D lineage. Lesions larger than 4.0 cm were the majority from 37 samples (64.9%). Clinical stage III was the most frequently observed stage out of 28 cases (49.1%) . 2 for 6 weekly cycles, which is associated with conventional external radiotherapy (teletherapy). The dose varied between 45 Gy and 50.4 Gy in 25 to 28 h fractions with high dose-rate brachytherapy and a dose of 28 to 30 Gy at Point A. The treatment was generally well tolerated; the highest toxicity reported was gastrointestinal grade II in 12 patients (50.0%). There were few grade III reactions, which resulted in the necessity of halting treatment.Of the 118 patients, about 24 women (20.3%) underwent treatment with chemotherapy, teletherapy, and brachytherapy and were evaluated regarding their responses at their first follow-up visits. The treatment performed consisted of chemotherapy, based on cisplatin, at a dose of 40 mg/mAs for evaluating the type of HPV, twelve women had HPV-16, two women had HPV-18, four were HPV negative, and the rest, with one sample each, had HPV-9, HPV-31, HPV-33, HPV-35, HPV-58, and co-infection.The return for the assessment of responses to treatment occurred at 110.3 days, on average. Due to the reduced number of patients, the categories for partial response, stable disease, and disease progression were unified to be considered a “present tumor”, while the complete response category was considered an “absent tumor”.In this group of 24 patients, it was observed that 17 patients (70.8%) had a complete response to treatment on their first return visit. Ages ranged between 25 and 79 years, with a mean age of 52.5 years. A total of seven women (29.28%) had anemia, with a hemoglobin value below 10.0 g/dL, requiring a blood transfusion. About 20 specimens (83.3%) displayed squamous cell carcinoma. Tumors larger than 4.0 cm were the majority, at 13 cases (54.1%), and had a worse response to treatment than the group of patients with tumors measuring up to 4.0 cm. The analysis of the histological grade showed that the higher the grade, the greater the presence of a residual or recurrent tumor . Of the Of the 57 women who were identified as having the HPV-16 variant, a total of 11 patients underwent chemotherapy, external radiotherapy, and brachytherapy treatment—seven were from the European group, carriers of the A lineage, and four from the non-European group, two from the C lineage and two from the D lineage. The age range varied between 25 and 76 years, with an average age of 46.5 years. Squamous cell carcinoma was the most frequent histological type and was observed in 10 women (90.9%). The tumors were well advanced in nine women (81.8%) and measured more than 4.0 cm. Clinical stage IIIB was the most frequent in seven patients (63.6%). An assessment of the response to treatment took place three months after its completion. A complete response occurred in nine patients (81.8%), five of whom were from the A lineage, two from the C lineage, and two from the D lineage . Cases oAmong the works carried out in Brazil, the research carried out in Belém, Pará, stands out, where, in a population of 63 cases of invasive cervical cancer infected by HPV-16, 57 samples were obtained with the following lineage prevalence: A = 45.6%; B = 1.7%; C = 1.7%; and D = 50.8%. Also noteworthy is a cohort study carried out in Rio de Janeiro (RJ), where, in 334 samples of cervical cancer with the presence of HPV-16, the following frequency of strains was observed: A = 64.9%; B = 2.9%; C = 2.9%; and D = 29.0% ,25. In tThe variability in the genetic material of HPV-16 variants could provide a difference in the prevalence of histological tumor types, which is similar to what occurs in the different types of HPV, where the frequency of adenocarcinoma is higher in HPV-18 than in HPV-16 . A studyThere is strong evidence showing that non-European HPV-16 variants have a higher oncogenicity due to their association with high-grade lesions of the cervix and invasive tumors ,30,31,32Cisplatin-based chemoradiotherapy has become a cornerstone in the treatment of advanced cervical carcinoma over the last two decades. The quasi-simultaneous publication of randomized trials demonstrates an improvement in disease-free survival and overall survival ,35,36. MSince patients with the same pathological factors do not react the same way to the same therapy and the human papillomavirus is the most common origin of all cervical cancers, it has been hypothesized that these types and variants could be used as prognostic factors to estimate an individual’s response to treatment and survival. The use of the HPV type as a prognostic factor remains controversial; some studies demonstrated a worse prognostic for HPV-18-infected patients , while oA few studies have addressed the association between HPV variants and their response to chemoradiotherapy. The literature suggests that European human papillomavirus variants have a better response to chemoradiotherapy. As Moreno-Acosta (2017)  reportedDespite the literature registering a worse evolution in non-European strains of HPV-16, in our study, it was the European group that registered the worst response, with one case of partial response and another case of disease progression. The limited number of patients did not allow the degree of influence of the intratype variant to be precisely defined in response to treatment with chemotherapy and radiotherapy. Conducting studies with a larger number of patients could better answer this question. A major challenge that further studies still encounter is the situation of the state itself, as one of the poorest in the country, with a low HDI and few specialized services for cancer treatment that mostly serve a poor population. This causes delays and difficulty in accessing health care services with consequent worse results regarding the treatment of cancer.Regarding the variants of HPV-16, A lineage dominated by 33 samples and squamous cell carcinoma was the most frequent of the four lineages. Among patients with HPV-16 variants who underwent treatment with chemotherapy, radiotherapy, and brachytherapy, it was observed that most achieved a complete response, with cases of partial response and disease progression occurring only in patients carrying the A lineage.The small number of patients studied and the irregular distribution of lineages evaluated do not permit a stable association between HPV-16 lineages and their response to treatment. A multi-institutional cohort study, with a larger number of patients addressing various HPV-16 intratype variants, should resolve this issue.