There is increasing support for HPV vaccination in the pharmacy setting, but the availability of the HPV vaccine is not well known. Additionally, little is known about perceptions of medical providers regarding referring patients to community pharmacies for HPV vaccination. The purpose of this study was to determine HPV vaccine availability in community pharmacies and to understand, among family medicine and obstetrics–gynecology providers, the willingness of and perceived barriers to referring patients for HPV vaccination in a pharmacy setting. HPV vaccine availability data were collected from pharmacies in a southern region of the United States. Family medicine and obstetrics–gynecology providers were surveyed regarding vaccine referral practices and perceived barriers to HPV vaccination in a community pharmacy. Results indicated the HPV vaccine was available in most pharmacies. Providers were willing to refer patients to a community pharmacy for HPV vaccination, despite this not being a common practice, likely due to numerous barriers reported. Pharmacist-administered HPV vaccination continues to be a commonly reported strategy for increasing HPV vaccination coverage. However, coordinated efforts to increase collaboration among vaccinators in different settings and to overcome systematic and legislative barriers to increasing HPV vaccination rates are still needed. Human papillomavirus (HPV) is the leading cause of most anogenital  and oropharyngeal cancers in both men and women, and the number of cancer cases linked to HPV has increased significantly over the past 15 years ,3. HPV-rTo address vaccination shortfalls, the President’s Cancer Panel (2018)  and NatiWhile pharmacies could potentially serve a powerful role in providing HPV vaccine access, administration, and series completion, relatively little is known about the willingness of physicians to refer patients to a pharmacy setting for HPV vaccination. Campos-Outcalt et al. (2010) reported that 34.2% of family physicians referred adult patients to a pharmacy for routinely recommended vaccines, but the authors did not report if they would refer adolescents and/or adult patients to a pharmacy setting for HPV vaccination specifically . A recenThe purpose of this study was to determine HPV vaccine availability in community pharmacy settings in a southern region of the United States. Additionally, this study aimed to understand, among family medicine and obstetrics–gynecology providers, the willingness of and perceived barriers to referring patients for HPV vaccination in a community pharmacy setting. This was accomplished by surveying family medicine and obstetrics–gynecology providers at a single academic medical center in the same geographic region.The availability of the HPV vaccine in the pharmacy setting was determined by the percentage of pharmacies that administer and stock the HPV vaccine. To accomplish this, a list of all pharmacies in a southern region of the United States (consisting of 17 counties in Eastern Tennessee) was generated. First, a list of zip codes for the target counties was generated and then an online search for pharmacies located in those zip codes was performed. Each pharmacy was called by a research team member acting as a “secret shopper”, where the team member acted as a customer inquiring about pharmacy services from October 2020 through April 2021. A standardized script for data collection was developed primarily based on study outcomes, including HPV vaccine availability and other measures of accessibility . The script was discussed and confirmed by consensus among coauthors . Using this standardized script, data regarding HPV vaccine availability were collected. The pharmacy staff member was first asked if the pharmacy administered the HPV vaccine. If the pharmacy stocked the HPV vaccine, they were then asked how soon one could get the HPV vaccine at their location, and if an appointment was required. Pharmacies were deemed “successfully contacted” if a research team member was able to call the pharmacy and get a definitive answer to any of the HPV vaccine-related questions. All pharmacies were considered in analyses. Up to three attempts were made to contact each pharmacy.To better understand the impact of pharmacy type on HPV vaccine availability, pharmacies were categorized into the following groups: single independent, multiple independent, regional chain, grocery store chain , national chain , and mass merchandiser . To interpret the impact of pharmacy geographic location, categorizations of rural versus nonrural were created for each pharmacy location’s zip code based on Health Resources and Services Administration’s Federal Office of Rural Health Policy (HRSA FORHP) designations .An electronic survey was adapted from a previously published survey on adult immunization and preventative care practices by Hurley et al. . The surData analysis was primarily descriptive, using categorical data, means, and frequencies to determine vaccine availability and accessibility. Chi-squared analyses determined if HPV vaccine availability differed by pharmacy type and geographic location and if pharmacy type differed by geographic location. To determine HPV vaccine availability in the family medicine and obstetrics–gynecology providers’ practices and to understand HPV vaccine referral practices, survey data analysis was primarily descriptive, using categorical data, means, and frequencies. Data were analyzed using Microsoft Excel (Office 365) and SPSS .A total of 233 out of 240 (97.1%) pharmacies were successfully contacted. Characteristics of the pharmacies contacted are presented in p < 0.01) across pharmacy type (p = 0.704). Additionally, there were no significant differences in pharmacy type when stratified by geographic location (p = 0.704).HPV vaccine availability differed significantly , and the age of the respondents ranged from 26 to 69 years of age (mean = 35.9 ± 10.6 years). In terms of role, 55.0% (n = 33) were resident physicians, 41.7% (n = 25) were attending physicians, and 3.3% (n = 2) were midwife practitioners.The survey was distributed to 70 family medicine and Ob/Gyn providers; 60 providers completed the survey (85.7% response rate). Among the respondents, 34 (56.7%) were affiliated with the Department of Family Medicine at the University of Tennessee Graduate School of Medicine and 26 (43.3%) were affiliated with the Department of Obstetrics and Gynecology at the same institution. The majority identified as female (n = 59) respondents reported their practice administers the HPV vaccine, and 95.0% stock the vaccine. When asked if they had ever referred a patient to receive an ACIP-recommended vaccine outside of their practice, 81.7% (n = 49) reported they had referred a patient for vaccination. When asked specifically if they have ever referred a patient for HPV vaccination outside of their practice, 20.0% (n = 12) had referred a patient age 11–18 years, 21.7% (n = 13) had referred a patient age 19–26 years, and 20.0% (n = 12) had referred a patient age 27–49 years. Among those that had ever referred a patient for HPV vaccination outside of their practice, over 90.0% referred patients to a local health department for HPV vaccination and did so across all patient age groups. Regarding referrals to a community pharmacy for HPV vaccination, 50% of those ever referring a patient for HPV vaccination referred a patient age 27–49 years, 53.8% referred a patient age 19–26 years, and 33.3% referred a patient age 11–18 years.Most respondents indicated their practice administered and stocked the HPV vaccine. Nearly all  reported they had prescribed the HPV vaccine for patients age 19–26 years, followed by 5.0% (n = 3) and 3.3% (n = 2) for patients age 27–49 and 11–18 years respectively. Most providers (>90%) were willing or very willing to refer an eligible patient to receive an HPV vaccination at a community pharmacy across all age groups  of providers answered, “I do not know”. Among the few respondents  that provided a numeric answer to the question regarding the percentage of pharmacies that administer the HPV vaccine, answers ranged from 25% to 85%, which was similar to the answers provided in response to the question of percentage of pharmacies that stock the HPV vaccine (ranging from 10% to 90%).When asked what percentage of pharmacies in their region administer and stock the HPV vaccine, 88.3%  administer and stock the HPV vaccine. Family medicine and obstetrics–gynecology providers surveyed in this study were willing to refer patients to a community pharmacy for HPV vaccination, despite this not being a common practice. Most providers did not know the extent to which community pharmacies in their region administered and/or stocked the HPV vaccine. Providers also reported several perceived barriers to referring patients for HPV vaccination in a pharmacy setting. The most common barriers expressed included their desire for patients to be vaccinated in their office; concern that patients would not complete the HPV vaccine series if referred outside their practice for vaccination; providers not knowing or having documentation of vaccination if performed in a pharmacy setting; and potential financial burdens for patients, associated with lack of insurance coverage, for the HPV vaccine in a pharmacy setting.In the current study, a larger proportion of pharmacies (60.1%) reported administering the HPV vaccine  comparedReports indicate HPV vaccination coverage is lower in rural areas, despite these areas having higher rates of HPV-associated cancers ,8. In thIn the current study, family medicine and obstetrics–gynecology providers were willing to refer patients to a community pharmacy for HPV vaccination, despite this not being a common practice. A study by Hurley et al. (2014) reported on vaccination referral practices by alternate vaccinators, including general internists and family medicine providers, where financial barriers made them less likely to stock and administer vaccines . AlthougIt is worthwhile to mention that among the providers surveyed in the current study, none of them perceived HPV vaccination as outside the scope of a pharmacist. This suggests the training and knowledge of a pharmacist surrounding the HPV vaccine may not be problematic for many family medicine and obstetrics–gynecology providers. Overall, these findings are in contrast to a study by Welch et al. (2003) that found most family medicine physicians were neither very knowledgeable about nor supportive of pharmacists as vaccinators . It is pWhile the majority of pharmacies in the current study had the HPV vaccine available, the majority of providers in the current study were not actively referring patients to a pharmacy setting for HPV vaccination. Providers reported concerns their patients may not complete the HPV vaccine series if referred outside of their office for vaccination and expressed concern they would not be informed whether their patients received vaccines in a pharmacy setting . The lacIn the current study, we did not specifically ask providers to distinguish their opinions and/or practices regarding HPV vaccine series initiation versus booster. For example, it is possible some providers prefer to administer the first HPV vaccine dose that a patient receives in their clinic, but would be willing to refer patients to a pharmacy setting for HPV vaccine series completion. Additional studies are needed to determine if providers might be more willing to refer patients to a pharmacy for HPV vaccine series completion and to determine the rate of follow-up for HPV vaccination among patients that are referred to a community pharmacy for HPV vaccination series completion. A recent study by Douchette et al. (2019) described a coordinated delivery of an HPV vaccine program using a clinic–pharmacy partnership. In their study, less than 50% of patients referred to a pharmacy received an HPV vaccine . HoweverThis study has limitations. These results may not be generalizable beyond this specific region in the Southern United States, as HPV vaccination uptake and accessibility are impacted by several factors that are state- and region-specific. These may include legislation and policies regarding HPV vaccination, social and environmental factors, religiosity, political ideology, and vaccine hesitancy. However, these data suggest that more research is needed to better understand perceived barriers and opportunities for HPV vaccination among providers in a variety of clinical settings. The providers included in the current study were from a single academic institution, working in clinics that administer and stock the HPV vaccine. It is possible that providers working in different settings would not be as willing to refer patients to a pharmacy setting for the HPV vaccine. Future work should include providers that are not affiliated with an academic medical center and those that do not work in practices that administer and stock the HPV vaccine. Finally, this study did not attempt to evaluate pharmacists as facilitators of HPV vaccines or their comfort in counseling patients about HPV vaccination. Nor did this study attempt to evaluate perceptions of facilitators to HPV vaccination in the pharmacy setting among family medicine and obstetrics–gynecology providers. Additional studies are needed to understand barriers and overcome obstacles to HPV vaccination, particularly in the community pharmacy setting.Findings suggest that the HPV vaccine is commonly available in nonindependent pharmacies in Eastern Tennessee. Family medicine and obstetrics–gynecology providers report they are willing to refer patients for HPV vaccination in a pharmacy setting; however, several barriers were reported that might limit this practice. While pharmacist-administered HPV vaccination continues to be a commonly reported strategy for increasing HPV vaccination coverage and the availability of the HPV vaccine in the pharmacy setting is common, coordinated efforts to increase collaboration among vaccinators in different settings and overcome systematic and legislative barriers to increasing HPV vaccination rates are still needed.


In Hong Kong (HK), a single-cohort vaccination program for 10–12-year-old girls with the 9-valent human papillomavirus (HPV) vaccine  has been launched. This study assessed the public health impact and cost-effectiveness of implementing routine 9vHPV vaccination (12-year-olds) with or without catch-up 9vHPV vaccination (13–18-year-olds) in HK.The health impact and costs of implementing routine 9vHPV vaccination with or without catch-up vaccination over a 100-year time horizon were evaluated using a validated HPV-type transmission dynamic model adapted to the HK population; analyses were performed from a healthcare payer perspective. Routine vaccination (12-year-old girls) and catch-up vaccination (13–18 years) assumed vaccine coverage rates of 70% (base case) and 30%, respectively. The model also assumed herd immunity, lifelong vaccine protection, a discount rate of 3%, and a cost per dose of HK dollars (HKD) 858 [United States dollars (USD) 110] and HKD 1390 (USD 179) for the 2-valent HPV (2vHPV) and 9vHPV vaccines, respectively. HPV disease-related incidence and the incremental cost-effectiveness ratio (ICER) per quality-adjusted-life-year (QALY) were estimated. Cost-effectiveness was determined at a ceiling threshold of HK dollars (HKD) 382,046  or 1.0 times the gross domestic product per capita of HK.Compared with routine 9vHPV alone, routine plus catch-up 9vHPV is projected to reduce cervical cancer incidence by 3.4%. Routine plus catch-up 9vHPV will also reduce genital warts incident cases for males/females by 2.6%/5.4%. The incremental cost-effectiveness ratios were HKD 29,911 (USD 3847)/quality-adjusted life-year (QALY) for routine plus catch-up 9vHPV versus routine 9vHPV alone and HKD 25,524 (USD 3283)/QALY for routine 9vHPV alone versus screening only. Sensitivity analyses indicated that routine plus catch-up 9vHPV compared with routine 9vHPV alone remained cost-effective at coverage rates of 30% and 90%.This analysis predicts that the current HK vaccination strategy can be considered cost-effective and will provide maximum health benefit. These results support addition of the routine 9vHPV vaccine with or without catch-up 9vHPV vaccination to the regional vaccination program in HK.The online version contains supplementary material available at 10.1186/s12962-021-00328-x. Human papillomavirus (HPV) infection causes almost all cases of cervical cancer and is relevant in other cancers, including anal, vulvar, vaginal, penile, and head and neck . These cCervical cancer is the ninth most common cancer and the ninth leading cause of cancer-related deaths among females in Hong Kong, with crude and age-standardized incidence rates of 12.9 per 100,000 females and 7.6 per 100,000 females, respectively . The oveWorldwide, the five most prevalent types associated with cervical cancer are HPV 16/18/45/31/33, although geographic variations exist .There are currently two vaccines available for the prevention of HPV-related diseases on the market in Hong Kong. The 2-valent HPV (2vHPV) vaccine protects against HPV 16/18, responsible for 70% of cervical cancer cases globally .Both the World Health Organization and the Centre for Health Protection in Hong Kong recommend HPV vaccination along with regular screening for the prevention of cervical cancer , 11. In The Hong Kong government launched a vaccination program with the 9vHPV vaccine during the 2019/2020 school year in all eligible female primary school students in grades 5 and 6. An interim target vaccine coverage of 70% for the 2-dose HPV vaccination schedule was set by the Hong Kong government, with preliminary data reporting a vaccine coverage rate of 85% for the first dose as of December 31, 2020 . The decGiven the high prevalence of HPV 52/58 in Hong Kong, the low historical coverage of HPV vaccination, and plans for the Hong Kong government to introduce a routine HPV vaccination program, there is a need to determine the public health and economic impact of school-based 9vHPV vaccination. We use a model to assess every next cohort at 12 year olds receiving the vaccination with continued coverage of 100 years. Therefore, the aim of this analysis was to assess the impact of a school-based strategy comprising two-dose 9vHPV routine vaccination of 12-year-old girls with or without catch-up 9vHPV vaccination among females aged 13–18 years (two-dose catch-up among those aged 13–14 and three-dose catch-up with 9vHPV vaccination among those aged ≥ 15 years) along with screening in the Hong Kong setting.A previously validated HPV-type transmission dynamic mathematical model simulating the natural history of HPV infections and estimating the cost associated with HPV-related diseases  was adapThe target population for routine vaccination was 12-year-old girls, whereas catch-up vaccination was considered for females aged 13–18 years. The health impact was assessed for the entire Hong Kong population across all ages. Costs were assessed using a healthcare payer perspective and impact was measured over a 100-year time horizon because this was considered an appropriate time frame from which the system approached steady state and most benefits and costs of vaccination could be realized. The median age of diagnosis is 49 years for cervical cancer and 62–68 years for other HPV-associated cancers . Given tThe vaccination scenarios compared include: (1) screening only, (2) routine 9vHPV vaccination (routine 9vHPV) along with screening, and (3) routine plus catch-up 9vHPV vaccination (routine plus catch-up 9vHPV) along with screening. The focus of this paper will be on routine 9vHPV vaccination with or without catch-up 9vHPV vaccination along with screening.The age-structured mathematical model  is a sinThe model structure, equations used, and assumptions have been previously described in detail . At an aThe model comprised three connected modules: (1) a demographic variables model describing the age structure of the population  and behavioral variables describing sexual activity; (2) an epidemiologic model simulating the transmission of HPV 6/11/16/18/31/33/45/52/58, occurrence of genital warts, precancers such as CIN 1/2/3 and vaccine type-related cervical cancer; and (3) a disease variables model describing screening rates, HPV infection, and HPV-related diseases .The mathematical model simulated and tracked various outcomes, including numbers of cases of precancers , cervical cancer, vaginal/vulvar cancer, and anal cancer. The model also estimated quality-adjusted life years (QALYs) and total costs, including vaccine-preventable disease costs, and vaccination costs. The incremental cost-effectiveness ratio (ICER) was estimated as the ratio of incremental cost to incremental QALYs. Cost-effectiveness was determined at a ceiling threshold of Hong Kong dollars (HKD) 382,046  or 1.0 times the gross domestic product per capita of Hong Kong; this threshold reflected the maximum willingness of decision-makers to pay for an additional QALY .Variables input into the model are shown in Table HPV vaccination coverage varies by country. Given that this would be a novel program in Hong Kong, we assumed a 70% coverage in 12-year-old girls for routine vaccination for the base case. We assumed 30% coverage in females aged 13–18 years for catch-up vaccination.The model considered oncogenic HPV 16/18/31/33/45/52/58 for cervical cancer, anal cancer, and CIN 1/2/3, as well as nononcogenic HPV 6/11 for genital warts. For all other HPV-related diseases , the model only considered HPV 16/18.The model also assumed herd immunity, lifelong duration of vaccine protection, a discount rate of 3% for costs and QALYs, and a cost per dose of HKD 858 (USD 110) and HKD 1390 (USD 179) for the 2vHPV and 9vHPV vaccines, respectively. The cost per dose includes the cost of the vaccine plus the administration fee.Inputs used to calibrate the model include population size (2016 data) ; incidenDeterministic one-way sensitivity analyses were conducted to assess the sensitivity of ICER values to variables that have been shown to be impactful to cost effectiveness. One variable was routine vaccination coverage, which was assessed at rates of 30% and 90%. Rationales for selecting different coverage rates: (1) a rate of 30% was chosen, because the HPV catch-up program is more likely to be a public–private partnership with private clinics rather than school-based. As a result, a much lower vaccine uptake rate is expected, and (2) a rate of 90% was based on historical data showing that school-based programs of some vaccines  can reach VCR as high as 90% in Hong Kong . SensitiCompared with routine 9vHPV alone, routine plus catch-up 9vHPV is projected to prevent 769 (3.4% reduction) cases of cervical cancers, over 100 years Table . The modCompared with routine 9vHPV alone, routine plus catch-up 9vHPV will also result in 3.1%, 3.4%, and 3.0% reductions in the incidences of vaginal cancer, vaginal intraepithelial neoplasia 2/3, and vulvar cancer, respectively  (Table Vaccine-preventable disease costs were reduced by 2.1% [approximately HKD 61.4 million (USD 7.9 million)] for routine plus catch-up 9vHPV versus routine 9vHPV alone  and HKD 25,524/QALY (USD 3283/QALY), respectively  compared with routine female-only vaccination with 2vHPV  with or without catch-up vaccination .Our findings indicate that 9vHPV routine plus catch-up vaccination of females only yields the most public health benefits  and may be cost-saving relative to the two alternative options  included in this analysis. Sensitivity analyses at assumed vaccination rates of 30% and 90% also demonstrated that the model findings were robust to changes in vaccination coverage. Projections of reduced HPV-related disease incidence and cost-effectiveness with routine 9vHPV vaccination and catch-up compared with screening only in this analysis provides a rationale for implementing a regional vaccination program in 12-year-old females in Hong Kong. Given that the ideal scenario is completion of full-course HPV vaccination prior to sexual debut, the low rates of sexual activity among secondary-school students  in Hong Kong  further The cost-effectiveness of catch-up HPV vaccination programs have been previously evaluated, with most studies demonstrating that catch-up vaccination is cost-effective in females aged 12–18 years . HoweverThe current analysis demonstrates that a routine 9vHPV vaccination program for girls aged 10–12 years with or without catch-up 9vHPV vaccination for females aged 13–18 years is cost-effective. Routine plus catch-up 9vHPV vaccination is estimated to provide an additional 2.1% reduction [approximately HKD 61.4 million (USD 7.9 million)] in vaccine-preventable disease costs over routine 9vHPV vaccination alone, resulting in an ICER of HKD 29,911/QALY (USD 3847/QALY). Tay et al. reported similar findings using a validated HPV transmission dynamic model to determine the economic impact of 9vHPV vaccination over the 4vHPV and 2vHPV vaccines in Singapore for females aged 11–12 . The stuOur estimates of cost-effectiveness of the 9vHPV vaccine are conservative because our model did not account for indirect costs and, in its current form, only models all nine types found in 9vHPV for cervical and anal cancer. For all other cancers, it models only HPV 16/18. A subgroup analysis of 9vHPV vaccination in Asian participants from two international studies (N = 2519) found that HPV 31/33/45/52/58–related disease was prevented with > 90% efficacy  . The higA limitation of this study is that it does not account for potential changes to cervical cancer screening with the introduction of routine HPV vaccination. Additionally, there are limited data on the incidence of genital warts in the Hong Kong population because of the variable spectrum of disease manifestation, potential embarrassment for patients, and the transient character of the disease . The modThe model also assumed no cross-protection against HPV types not targeted by HPV 16/18. Clinical trial results show that the 2vHPV vaccine provided lower and less consistent protection against HPV types 31/33/45 and lasted for a shorter duration than against directly targeted HPV types (HPV 16/18) . EvidencThis analysis predicts that the current Hong Kong vaccination strategy can be considered cost-effective and will provide maximum health benefit, with greatest reductions in HPV-related disease incidence compared with all other vaccination strategies considered. Considering the low uptake of cervical screening and the high prevalence of HPV types 52/58 in Hong Kong, preventing HPV-related disease represents a concern for the Hong Kong government. These results support the incorporation of a catch-up strategy to the current routine 9vHPV female vaccination program for 12-year-old females in Hong Kong.Additional file 1: Table S1. Model Input Variables Implemented in Transmission Dynamic Model. Table S2. Cost-Effectiveness Analysis of the Routine 2vHPV Female-Only Vaccination Strategy vs Screening Only. Table S3. Sensitivity Analyses for Cost-Effectiveness of HPV Vaccination Strategies. Figure S1. Estimated healthcare costs avoided over 100 years by HPV type with routine plus catch-up FOV with the 9vHPV vaccine versus (A) FOV with the 2vHPV vaccine and (B) FOV with the 9vHPV vaccine.


This is particularly important for women living with human immunodeficiency virus (WLHIV) infection because of their exceptional risk for cervical cancer. The availability of HIV programmes in low- and middle-income countries (LMICs) provide unique opportunity for possible introduction “human papillomavirus (HPV) screening followed by visual inspection after application of acetic acid (VIA) with same day treatment of eligible patients”. This study piloted this concept.in this prospective, cohort study, 98 WLHIV had HPV and VIA screening for cervical precancer lesions in a HIV clinic in Nigeria. Participants positive to HPV and/or VIA had biopsies from the visible lesions or quadrant of transformation zone. Participants positive to VIA and/or HPV16 or HPV18/45 had same-day thermal ablation treatment and the number of cases documented. The HPV, VIA and scenario of HPV followed by VIA results were compared with histologically confirmed cervical lesion grade 2 or worse statistically.same day treatment was achieved in 95.0% of eligible cases. Statistically, sensitivity and specificity of VIA was 25.0% and 50.0% and HPV had 95.5% and 75.0%, respectively. In the HPV screening with VIA triage, sensitivity dropped to 45.5% but specificity improved to 100.0%.triaging HPV positive test with VIA for same-day treatment in cervical precancer screening among PLWHIV looks feasible. The improved specificity will reduce the overtreatment rate, loss to follow-up associated with repeat clinic visits and improve completion of continuum of care. Invasive cervical cancer (ICC) occurs about 7.9 times more among women living with HIV (WLHIV) than general population . It is tTo reduce this burden of ICC among WLHIV in Nigeria, cervical precancer screening and treatment was prioritized as routine service among WLHIV by Centre for Disease Control and Prevention (CDC) in Nigeria in 2019. The screening uses visual inspection after application of acetic (VIA), an effective and easy to implement method for low- and middle-income countries (LMIC) ,7. The mTo achieve this single clinic-visit for HIV and cervical cancer prevention services will require similarly effective and easy to perform HPV testing method with short turn-around time (TAT). The point of service GeneXpert HPV testing platform provides this possibility. The GeneXpert HPV test is a multiplexed, cartridge-based real-time polymerase chain reaction assay with integrated sample preparation that detects 14 hr-HPV types, grouped into 5 channels HPV 16; HPV 18 and/or 45; HPV 31, 33, 35, 52 and/or 58 (P3); HPV 51 and/or 59 (P4); and HPV 39, 56, 66 and/or 68 (P5) . The TATHowever, the efficacy of this two-stage, same day strategy among HIV population remains unclear. This study aimed to pilot the concept of HPV-based primary cervical precancer screening, same day triage of positive cases with VIA for ablative treatment among HIV positive women.Study design and setting: this is a prospective, cohort study that evaluated the feasibility of HPV-based primary screening for precancer lesions of the cervix followed by triage of positive cases to determine those that were eligible for same day treatment. The study was conducted between January and March 2020 in a large antiretroviral treatment (ART) programme situated at Infectious Disease Institute, College of Medicine, University of Ibadan, Nigeria.Study population: the study population were women living with HIV (WLHIV). The inclusion criteria were prior sexual exposure irrespective of age, CD4 cells count, viral load, ART treatment status and participation in the routine cervical precancer screening service in the ART programme. Those with previous treatment for cervical diseases and those diagnosed with suspected cervical cancer at presentation for screening were excluded from participation. A consecutive enrolment of purposively sampled 100 participants was done to pilot this test-of-concept study.Data collection: each participant underwent routine VIA by trained screening nurse , 72.4% had at least secondary school education, 71.4% were currently married, 69.2% reported more than one lifetime sexual partner and none reported previous cervical screening services uptake : all the 24 participants with positive HPV results and 20 participants that were VIA-positive had biopsies of VIA positive areas and the quadrants of the cervix for those with no obvious VIA positivity to ascertain the validity of HPV screening. Among the 22 participants with CIN 2+, VIA correctly identified the cases in 11/22 (50.0%) and GeneXpert HPV in 21/22 (95.5%). However, with scenario of GeneXpert HPV primary screening with VIA triage for same day treatment identified all the 22 (100.0%) cases with CIN 2+. In identifying cases that were truly negative (specificity), VIA identified 3/12 (25.0%) cases, HPV identified 9/12 (75.0%) cases and in a possible scenario of HPV primary screening and VIA triage identified all the 12 cases (100.0%) that were ≤CIN 1 (e ≤CIN 1 . The oveFeasibility of “same-day” treatment: thirty-three of the 34 participants (97.1%) that were HPV and/or VIA positive had same day cervical biopsies with histology of CIN2+ in 21 cases and the participants that was VIA positive but had biopsy one week later also had CIN2+. Overall, 19 of the 20 (95.0%) eligible participants had same day thermal ablation treatment.This test of concept of HPV-based cervical precancer screening and triage of positive cases with VIA for same day treatment if eligible is the first attempt in our environment. This study showed that this strategy is feasible in that 95.0% of the eligible participants had thermal ablation treatment same day. This represents the primary intention of this concept study. This is achievable because of the use of HPV test platform with short turn-around time with positive cases triaged with a test that provided immediate results.The GeneXpert HPV performed quite as well as previously documented in other studies as a screening test -20. Our Our study found that the gain in specificity by adding VIA to HPV testing was at the expense of loss of sensitivity. This might be a problem in mass screening program. However, in a facility based routine screening, this might not be of particular concern especially with a positive predictive value of the sequential testing of 100%.A major strength of this work is the use of histology as reference standard and reporting by an experienced pathologist with many years of collaboration -29, unliHPV allowed adequate detection of CIN2+ in our analyses, resulting in a sensitivity of 95.5%% (95% CI: 79.6 - 100%) and a specificity of 75.0% (95% CI: 70.6 - 78.1%). This sensitivity is comparable with what have been reported in some other studies in Africa among HIV population . In addiOur study was limited by the small size of the study population. Accuracy estimates based on a larger number of women would have provided more robust and probably generalizable results. In addition, the reference standard of cervical biopsy was not performed in participants with negative HPV or VIA test results, suggesting that limiting the biopsies to women based on HPV and/or VIA-positive results identified most women with CIN2+ in only this subset of participants .This study demonstrated the feasibility of same day ablative treatment of eligible patients from HPV-based primary screening for cervical cancer with VIA triage. However, there is need to conduct a larger study to validate this concept. Such larger studies with well calculated sample size and adequate power will provide insight into some of the other issues that have come up from this pilot and make the results obtained more generalizable. Other potential benefits will include establishment of more cost-effective screening strategy of longer screening intervals for screen negative women.Cervical precancer screening using HPV test is the most sensitivity method;There is need to combine HPV screening with another screening method for effective identification of those that need treatment to avoid overtreatment with associated disadvantage;VIA is one of such methods advocated for LMIC where logistics of cytology remain difficult to overcome.The screening for cervical precancer lesions with HPV and triaging to same-day treatment using VIA in an HIV programme is feasible;The accuracy to identify patients that do not require treatment was improved by two stage screening using HPV followed by VIA thereby eliminating the problem of overtreatment;Overcoming the problem of loss to follow up with associated poor optimization of benefits of screening for precancer lesions of the cervix looks achievable with this strategy.


Vespula squamosa are typically headed by a single reproductive queen and survive for only a single season. However, in warmer climates, V. squamosa colonies sometimes persist for multiple years and can grow to extremely large size. We used genetic markers to understand patterns of reproduction and recruitment within these perennial colonies. We genotyped V. squamosa workers, pre‐reproductive queens, and males from perennial colonies in the southeastern United States at 10 polymorphic microsatellite loci and one mitochondrial DNA locus. We found that V. squamosa from perennial nests were produced by multiple reproductives, in contrast to typical annual colonies. Relatedness of nestmates from perennial colonies was significantly lower than relatedness of nestmates from annual colonies. Our analyses of mitochondrial DNA indicated that most V. squamosa perennial colonies represented semiclosed systems whereby all individuals belonged to a single matriline despite the presence of multiple reproductive females. However, new queens recruited into perennial colonies apparently mated with non‐nestmate males. Notably, perennial and annual colonies did not show significant genetic differences, supporting the hypothesis that perennial colony formation represents an instance of social plasticity. Overall, our results indicate that perennial V. squamosa colonies show substantial changes to their social biology compared to typical annual colonies and demonstrate variation in social behaviors in highly social species.Many social species show variation in their social structure in response to different environmental conditions. For example, colonies of the yellowjacket wasp  Vespula squamosa displayed remarkable variation in social behavior that resulted in extreme changes to colony structure and ontogeny. This shift in social strategy may help wasp societies survive and dominate the local environment when subject to variable conditions.Social species show variation in their social behaviors in response to environmental differences. We found that the social wasp  Individuals were preserved in 95% ethanol and transported to the laboratory for genetic analysis.2.2® protocol  and manual scoring of peaks. mtDNA amplicons were sequenced using the CB1 primer by Eton Biosciences.2.3V. squamosa colonies into this investigation for comparative purposes  within colonies contributed differentially to the production of gynes and workers. The resulting We then investigated the distribution of genotypes of workers, gynes, and males within perennial colonies to determine whether individuals of each caste were produced by more than one reproductive queen. For example, the presence of three homozygous genotypes among the workers or gynes, or three different alleles among the males, would indicate that these individuals arose from multiple reproductives. We then used the program COLONY   to determine the significance of the correlation between geographic and genetic distance.Then, we investigated whether the perennial and annual V. squamosa using the program GDA  and “colony within social form.” Estimates of theta for these levels  provided information of genetic differentiation of social forms, while controlling for genetic differences between colonies.Finally, we examined genetic differences between perennial and annual colonies of 2.4We obtained the sequence of 223 individuals from 8 perennial and 13 annual colonies at the PCR‐amplified cytochrome b fragment Table . MEGA X V. squamosa haplotype sequences, additional Vespula cytochrome b mtDNA sequences were downloaded from GenBank for inclusion in the analysis. These samples consisted of two additional Vespula squamosa sequences  for differences between social forms using a probability test.33.1p = .051, p = .9685, and p = .0584, respectively). Thus, we combined individuals from the MO parent and satellite nest together for all subsequent analyses.We identified one perennial colony, MO, that apparently had developed a small satellite colony near it Figure . A probap < .001). Thus, there is some evidence of genetic differences between castes in perennial colonies.We next investigated whether the distribution of gyne and worker genotypes within perennial colonies differed significantly. Our analysis uncovered evidence that the distribution of gyne genotypes differed significantly from that of workers in 3 of the 6 colonies .We next calculated the relatedness of nestmate workers, gynes, and males from perennial colonies Figure . We founV. squamosa social forms. Our analyses revealed that the mean number of alleles present within perennial V. squamosa individuals was double to triple the mean number of alleles in annual colonies at 6 of the 7 loci and differed significantly between social forms overall  except for LIST2019 (p = .0541). The effective number of alleles, however, did not differ significantly between the social forms, suggesting that many of the observed alleles in perennial colonies were present at relatively low frequency .We next investigated genetic differences between the perennial and annual FST between all pairs of colonies . Moreover, the pairwise FST values for intersocial form comparisons were more moderate and fell between the values for the annual and perennial colonies.Genetic differences between colonies were estimated by calculating s Figure . The FSp = .404, p = .541, p = .995, respectively). That is, colonies that were more distantly separated geographically from each other did not display significantly more genetic differentiation due to distance. Thus, overall, we find no evidence of population genetic isolation in V. squamosa.We used Mantel tests to investigate genetic isolation by distance for the annual and perennial colonies. Annual colonies, perennial colonies, and all colonies combined showed no evidence of genetic isolation by distance across their respective collection ranges (S). In contrast, there were substantial genetic differences among colonies within social form  had a similar haplotype diversity to perennial colonies (0.5641).We identified a total of five variable bases within our trimmed 338 bp sequence of the cytochrome b gene, indicating the presence of five unique haplotypes in our sequenced s Figure . OverallAll annual colonies displayed a single mitochondrial haplotype, which is to be expected in a closed system with a single reproductive queen. Notably, however, we also found that all individuals from 7 out of 8 perennial colonies possessed only a single haplotype, suggesting that all individuals belonged to a single matriline. The only multiple‐haplotype perennial colony (MA) contained a single worker that differed in haplotype from the rest of the sampled individuals in that colony. This haplotype was confirmed by re‐sequencing the individual in question.V. squamosa sorted into a monophyletic group when compared to the sequences from the outgroups V. maculifrons and V. germanica. We also investigated whether the social forms showed significant differences in mtDNA haplotype frequency using an abbreviated dataset consisting of only a single individual per colony. We found no significant differences in haplotype frequency between social forms using a test of genic differentiation (p = .2077).A maximum‐likelihood phylogeny was generated to understand the relationships among the five different haplotypes Figure . We foun4V. squamosa colonies. Our goal was to understand how the social structure of perennial colonies differs from that of typical annual colonies and provide insight into future changes in social behavior.The goal of this study was to gain a greater understanding of variation in the social structure of a highly social insect. We specifically investigated the social systems of large, perennial 4.1V. squamosa perennial colonies were always headed by multiple queens. The genotypes of sampled workers, gynes, and males were consistent with reproduction by multiple reproductive females. This was supported by maximum‐likelihood estimations of queen number that indicated that colonies could be headed by 20 or more queens. However, we note that the exact assessments of queen number are likely to be complicated by queen polyandry, suggesting that actual estimates of queen number should be viewed cautiously. Regardless, our data clearly demonstrate that perennial colonies are headed by many reproductive queens. This differs substantially from annual V. squamosa colonies, which are always headed by a single queen that produces all workers, gynes, and males as long as she is present  V. squamosa perennial colonies, including the multiple female reproductives, generally originate from their own parental nest.The overall result from our analysis of mtDNA was that workers, gynes, and males from perennial nests almost always possessed a singular mtDNA haplotype. There was a single worker from one perennial colony (MA) that possessed a mtDNA haplotype inconsistent with the rest of the colony. The importance of this individual is hard to interpret, as it could represent a rare event such as worker drift or even cross contamination. Therefore, overall, the data suggest that members of V. squamosa colonies recruit nestmate queens fits with general expectations from kin selection theory  or phenotypic plasticity. We attempted to explore this question by testing for genetic differences between the nuclear and mtDNA genotypes of annual and perennial colonies. We found no evidence of genetic differences between the social forms at either set of markers. In addition, there was no evidence of genetic isolation by distance within the social forms. Thus, overall, we find no evidence of genetic differentiation among the social forms. We note that this analysis, which includes the use of only a few genetic markers, is insufficient to provide a strong test of genetic differentiation between social forms. Nevertheless, our analysis can be viewed as providing preliminary insight into the question of whether annual and perennial V. squamosa colonies belong to the same gene pool, and our data are consistent with the idea that the perennial colonies represent an instance of phenotypic plasticity rather than evolution.We sought to investigate whether the formation of perennial V. squamosa social forms has not uncovered evidence of genetic differences at this time. But more in‐depth genomic analysis is needed to determine whether such genetic differences exist or whether they are likely to arise in the future.Previous investigations of other social species have sometimes uncovered evidence for a genetic basis to complex social behavior ; Formal analysis ; Investigation ; Methodology ; Writing – original draft . Henry G. Crossley: Data curation ; Methodology . Charles H. Ray: Investigation (supporting); Methodology (supporting); Resources (lead). Michael A. D. Goodisman: Conceptualization (lead); Formal analysis (supporting); Funding acquisition (lead); Investigation ; Project administration (lead); Resources (lead); Supervision (lead); Validation (lead); Writing – original draft .


Regard to this fact that the main transmission route of HPV and HHV-8 is via sexual activity, it is reasonable to speculate that coinfection of HPV and HHV-8 may have been played an important role in the development of cervical cancer. The aim of this study was to estimate the prevalence of HHV-8 and the frequency of HPV and HHV-8 coinfection in cervical samples of patients with cervical cancer and healthy individuals.In total, 364 samples from 61 patients with cervical cancer, 124 women with premalignant lesions, and 179 healthy individuals were investigated by nested-PCR.P = 0.308). The overall prevalence of coinfection between HHV-8 and HPV was shown to be 16.2%. The HPV prevalence was higher in HHV-8 positive samples than HHV-8 negative specimens in all three studied groups and this difference was reached a statistically significant level (P = 0.002). However, no significant differences were found between HHV-8 positivity and HPV genotypes (P = 0.08).The frequency of HHV-8 was found to be 22.9%, 17.7%, and 14.5% in cervical cancer, premalignant lesions, and normal specimens, respectively (Our results showed the higher rate of HHV-8 genome detection in cervical cancer group than control group. However, future studies with larger sample sizes and evaluation of expression of HHV-8 proteins are warranted. Cervical cancer is considered as the fourth most common cancer with an estimated 604,000 new cases and 342,000 new deaths worldwide in 2020 , 2. The Human papillomavirus (HPV) is the most prevalent viral sexually transmitted infection and is well-known as the etiological agent of cervical cancer . AlthougHuman herpesvirus 8 (HHV-8) has been documented to be the etiological agent of Kaposi’s sarcoma and two kind of lymphomas, including primary effusion lymphoma and Multicentric Castleman disease , 16. HHVRegard to this fact that the main transmission route of HPV and HHV-8 is via sexual activity, it is reasonable to speculate that coinfection of HPV and HHV-8 may have been played an important role in development of cervical cancer. To our knowledge, this is the first report of investigating the prevalence of HHV-8 in normal, premalignant, and malignant cervical samples among Iranian women. There are also few studies according to the HHV-8 prevalence in patients with cervical cancer in the world . The aimTo investigate the prevalence of HHV-8, a case–control study was designed. For the purpose of this study, 185 case samples  and 179 healthy individuals (negative pap-test result) were included. Regard to specimen types, all of 61 samples of patients with invasive cervical cancer and 53 samples of women with premalignant lesions were formalin-fixed paraffin-embedded tissues (FFPE) that were collected from Immam-Khomeini hospital in Tehran and Al-Zahra hospital in West Azarbayzan from 2017 to 2019. Seventy-one samples of women with premalignant lesions and all of 179 normal samples were Thin-Prep Pap Test specimens were obtained from three referral laboratories in Tehran from 2017 to 2019. Although the status of HPV infection and HPV genotypes in 114 FFPE specimens was unknown, they were previously characterized for 250 Thin-Prep Pap Test specimens. The mean age ± SD was 54.1 ± 13.4, 36.1 ± 9.4, and 36.6 ± 11.5 in women with cervical cancer, premalignant lesions, and normal cervix, respectively. All study participants gave informed consent to the study which was approved by the Local Research Ethics Committee  of Tehran University of Medical Sciences.Genomic DNAs from Thin-Prep Pap Test specimens were extracted using a High Pure Viral Nucleic Acid Kit  according to the manufacturer’s instruction. Extraction of DNA from FFPE specimens was achieved according to previous published procedure . Briefly2, 10 pmol of each primer, 50 mM of each dNTP, and 2 U of Taq DNA polymerase. PCR amplification cycles were as follow for the first and the second rounds: an initial 3-min denaturation at 95 °C, followed by 35 cycles of 95 °C for 30 s, 50 °C for 45 s, and 72 °C for 1 min (first round) and 35 cycles of 95 °C for 30 s, 52 °C for 40 s and 72 °C for 45 s (second round), and a final elongation for 5 min at 72 °C. A reaction mixture lack of DNA template, as a negative control, was included in each run of PCR. The PCR products were run on a 2% agarose gel.HPV DNA detection in all FFPE samples (114 samples) was carried out by nested-PCR using MY09/MY11 primer pair (outer primers) and GP5 + /GP6 + primer pair (inner primers) to obtain almost a 150 bp fragment of HPV L1 gene . The PCRhttp://www.ncbi.nlm.nih.gov/blast/).The PCR amplification products were sequenced using BigDye® Terminator v3.1 Cycle Sequencing Kit and a 3130 Genetic Analyzer Automated Sequencer as specified by Applied Biosystems manuals . Nucleotide sequences were edited with Bioedit software and converted to FASTA format. Then, sequences compared to other HPV types using the Blast server  using the XThe prevalence of HHV-8 in 364 cervical samples from 61 patients with cervical cancer, 124 women with premalignant lesions, and 179 healthy individuals were investigated in this study.The mean age ± SD was 54.1 ± 13.4, 36.1 ± 9.4, and 36.6 ± 11.5 in women with cervical cancer, premalignant lesions, and normal cervix, respectively.P = 0.308) (Table P = 0.98). Interestingly, no statistically significant differences were found between the prevalence of HHV-8 and sample types (P = 0.78) as HHV-8 was detected in 15.8% and 17.6% of FFPE and Thin-prep pap test samples, respectively .As shown in Table As presented in Fig. P = 0.08) (Table P = 0.0001) as coinfection with HPV 16/18 was more common in cervical cancer samples (78.6%) than premalignant (15.8%) and normal (20.8%) groups , respectively. However, no significant differences were found between HHV-8 positivity and HPV genotypes (P = 0.55). However, in three studied groups that were HHV-8 positive, a meaningfully significant difference was found regard to age groups  II–III and cervical cancer, respectively. HHV-8 DNA had been also detected in 9.2% and 14.3% of normal and CIN I samples, respectively . HHV-8 iIt is suggested in regions that the prevalence of HHV-8 is medium or low, oral shedding and heterosexual contacts are potential pathways for HHV-8 transmission , 27. A sA statistically significant difference was observed between the frequency of HHV-8 and HPV infection as the prevalence of HHV-8 was remarkably higher among HPV positive samples than HPV negative samples. In accordance to our data, a study from Spain was shown that HHV-8 was more common among HPV DNA-positive women (odds ratio = 2.5) and among women with an early age at first sexual intercourse (Odds ratio = 2.7) . HoweverIn this study, totally no significant differences were found between HHV-8 positivity and HPV genotypes. However, the prevalence of HPV genotypes was meaningfully different between cervical cancer patients and premalignant or normal subjects and this difference was statistically significant as HPV 16/18 was more prevalent in cervical cancer specimens (78.6%) rather than normal (20.8%) and premalignant samples (14.3%).HHV-8 infection synergistically with HPV can contribute to cervical carcinogenesis through several mechanisms. It is shown that HHV-8 coinfection in SiHa cell line could be promoted the increased expression levels of several inflammatory factors, including interleukin 6 (IL-6), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C–C motif) ligand 5 (CCL5), interleukin 8 (IL-8), macrophage migration inhibitory factor (MIF), and plasminogen activator inhibitor-1 (PAI-1) , 30. IndP = 0.015). While the most of normal (69.2%) and premalignant (54.5%) samples were in age group of < 40 years old, the most of malignant samples (78.6%) were found in group > 40 years old. These results are reasonable as the peak of cervical cancer incidence is shown to be in 55–65 year-old women in Iran [In three studied groups that were HHV-8 positive, a meaningfully significant difference was found regard to age groups ( in Iran . Regard  in Iran , 40.The most important limitations of this study were found to be the relatively small sample size.Our results showed higher rate of HHV-8 genome detection in cervical cancer group than premalignant and control groups. Moreover, our finding supports the likelihood of HHV-8 transmission through sexual route in Iranian population. However, future studies with larger sample sizes and evaluation of expression of HHV-8 proteins on cervical samples are warranted. It is also recommend that the frequency of HHV-8 shedding will be determined in saliva of all age groups to clarify the transmission routes of HHV-8 in Iran.


The study was to determine the practice desire, attitude and knowledge of mothers of adolescent girls on HPV vaccination in Western Kenya.this was a descriptive cross-sectional study design. Data was obtained using semi-structured questionnaires and analyzed using both descriptive and inferential statistics at 95% confidence level using the SPSS software version 22. A p-value ≤ 0.05 was considered statistically significant.ninety five percent of the mothers had intentions to vaccinate their daughters and also had a positive attitude and their response to HPV vaccination was significantly lower than those without intentions p=0.02, 95% CI, OR=0.48 (0.90-0.89). Vaccination against HPV was low at 9.4% with a mean age of 34 years. Our results found a high level of cervical cancer awareness (85.0%), HPV and vaccine awareness respectively . “Vaccination of my daughters will prompt early sexual activity and the cost of HPV vaccination being a barrier to vaccination” had a statistically significant influence on the practice of vaccination. Negative attitude to daughters´ early onset of sexual activity significantly reduced up take while positive attitude to cost of HPV vaccine significantly increased up take of HPV vaccination with p value of 0.007 and 0.04 respectively.awareness of HPV and HPV vaccine prevention is low among mothers of adolescent girls in Western Kenya. There was a positive attitude and high desire towards the use of HPV vaccination therefore a need for awareness, policy and unify efforts to reduce cervical cancer burden. Cervical cancer related deaths in 2018 accounted for 266,000 7.5%) of female cancer death worldwide with an estimated 528,000 new cases annually. In Kenya, cervical cancer is the second most frequent cancer after breast cancer and accounts for an average of 2000 deaths per year. Kenya has a crude incidence rate of 16.5 per 100,000 women and age standardized rate of 28.7 . Cervica% of femaHuman papilloma virus (HPV) is the most widespread sexually transmitted infection and studies have shown that 50-80% of sexually exposed are infected at least once in their life time , 7. HPV et al. (2005) and Harper et al. (2006) in their researches on prophylactic quadrivalent human papillomavirus  posited that the most effective preventive method against cervical cancer among adolescent girls and other women prior to sexual exposure is the primary prevention by the HPV vaccination [Villa cination , 15. Thecination . HPV vacHPV vaccination has been recommended for introduction into national immunization programs in various countries. HPV vaccine has been incorporated into the school vaccination program for young adolescent girls in some developed countries which include: USA, Australia, New Zealand and Sweden. This practice however faces the challenges which are common to new vaccines. Parental consent is needed for the vaccination of minors, for this reason, parental knowledge, attitude to the vaccine and acceptance to vaccinate their daughters would to a good extent determine the success of the HPV vaccination program. Factors influencing practice of HPV vaccination such as: vaccine awareness, child age, perceived access to the vaccine, societal norms, religious inclination, stigmatization against sexually transmitted infection, vaccine safety and suspect of potential long-term adverse outcome, perception about disease susceptibility and severity, interaction with clinicians, the need to involve the adolescent in decision and mother´s cervical dysplasia and cervical cancer experience are thought to influence the uptake of HPV vaccination in Kenya.The progress in the HPV vaccination programs and awareness creation about vaccination has remained slow in Kenya. Few studies in our environment have investigated the disposition, attitude, intention to vaccinate and practice of HPV vaccination of adolescent girls by their mothers. Few studies have evaluated the acceptability of the HPV vaccine in Kenya and we found no such studies in Eldoret in particular. Hence this study aimed at determining the knowledge, attitude, desire and practice of HPV vaccination of adolescent girls and factor that determine the intent and practice of HPV vaccination of adolescent girls by their mothers in Eldoret. In order to achieve the purpose of this study, the following research questions were answered: what is the extent of the practice of adolescent girls HPV vaccination by mothers in Eldoret? what is the level of Knowledge on cervical cancer, HPV and HPV vaccine? what is the attitude of mothers towards vaccination of their adolescent daughters? and what are the factors influencing practice of HPV vaccination among adolescent girls?This was a questionnaire-based cross-sectional survey carried out in Eldoret, Uasin Gishu County in Kenya at Moi Teaching and Referral and Gynocare Womens and Fistula Hospital. The study was conducted between January 2018 and July 2018. Eldoret is a principal city in Western Kenya. It is a capital of Uasin Gishu County with the location elevation varies from about 2100 metres above the sea level to more than 2700 metres (7000-9000 feet). Gynocare Womens and Fistula Hospital is a 100 bed hospital dedicated to fistula surgery, gynecological and obstetric care services. The hospital offers cervical cancer care. Moi Teaching Hospital is a 1000 bed national hospital dedicated to teaching and referral hospital in Eldoret. The reproductive health department has 45 beds dedicated to gynecology and 150 beds dedicated to obstetrics.The study was based on convenience sampling of consenting mothers who accompanied their daughters to gynecological and adolescents clinics. The study population included randomly selected mothers of adolescent girls as at the time of the administration of questionnaire aged above 18 years. Random sampling was used to determine the sample size and recruitment of the study participants. Random sample generator was used until the desired sample size was achieved.Face-to-face structured interviews were conducted by trained research assistants after the purpose of the study had been explained to the participants and their informed consent sought and gained. Women who did not give their consent were excluded from this study. Ethical approval was sought and given by the Institutional Research and Ethics Committee (IREC) and the Moi Teaching and Referral Hospital. IREC/2017/120.A standardized questionnaire assessing knowledge of HPV, cervical cancer, pap smear test, vaccine acceptability, and willingness to participate in HPV vaccination as well as demographic characteristics related to HPV and cervical cancer was administered to a total of 300 mothers of adolescent girls. The questionnaire was explained to those participants who could not read and understand English. This questionnaire consisted of 5 sections seeking information about the socio-demographic characteristics of the respondents such as age, marital status, religion, occupation and educational attainment, their knowledge of cervical cancer, HPV infection and HPV vaccination, and their attitude and practice of HPV vaccination of the daughters.The study was tested for validity: construct validity; establishing correct operational measures for the concepts being studied. Internal validity; for explanatory and casual studies only, not for descriptive or explanatory studies establishing a casual relationship, thereby certain conditions are shown to lead to another conditions. The depth of knowledge in the questionnaire was determined by grading respondent´s responses on knowledge into poor, good and excellent. Five points Likert´s scale was used to assess attitude; where various degrees of attitude were assessed using options of 1) strongly disagree; 2) disagree; 3) undecided; 4) agree; 5) strongly agree.In addition, the questionnaire was tested for reliability by using cronbach coefficient alpha to determine the internal consistency of the items. This method was used for estimating reliability of test scores by the use of a single administration of a test. Therefore, provided good measures of reliability because holding other factors constant, the more similar the test content and conditions of administration are, the greater the internal consistency reliability . Data was computed and analyzed using statistical software SPSS for windows version 22. Data was analyzed using descriptive and inferential statistics. Frequencies and percentages were determined where appropriate. Statistical significance was determined using p-value. P-value of 0.05 was considered statistically significant.Demographic characteristics of respondents: we sought to ascertain the demographic characteristics of the respondents and compare it with their knowledge, attitude, desire and practice of HPV vaccination on mothers and their adolescent girls and factors that determine the intent and practice of HPV vaccination of adolescent girls in Eldoret  and workshop/conferences (30.0%). With regard to risk factors for cervical cancer, the largest risk factors for cervical cancer reported by women were multiple sexual partners (35.5%). In addition, about 34.0% mentioned that early sexual intercourse while 20.0% identified HPV infection. Concerning on knowledge of HPV prevention measures, there was predominantly positive attitude towards the use of HPV vaccination for prevention of cervical cancer among respondents; hence the high rate of desire by mothers to vaccinate their daughters.Out of the 272/300 mothers who had positive attitude to HPV vaccination seen in this study, only 28/300 of them had actually had their daughters vaccinated. Vaccination practice of women with positive attitudinal response to HPV vaccination was significantly lower than those without p=0.02, 95% CI, OR=0.48 (0.90-0.89). Positive attitude significantly led to desire or intention to vaccinate daughters. P-values ranges from 0.00-0.04. The attitude of mothers to the statement “HPV Vaccination may lead to daughters early onset of sexual activity and HPV vaccination violates my cultural and religious beliefs and safety of the vaccine´s administration” was not statistically significant in influencing mothers desire to vaccinate their daughters against HPV. P=0.14 and 0.60 respectively. Only three attitudinal parameters; “vaccination of my daughters will prompt early sexual activity and cost of HPV vaccination being a barrier to vaccination” had statistically significant influence on the practice of HPV vaccination of daughters. Positive attitude to cost of HPV vaccine significantly increased up take of HPV vaccination of daughters while negative attitude to daughters early onset of sexual activity significantly reduced up take. P=0.04 and 0.007 respectively.This study describes the knowledge, attitude, desire and practice of HPV vaccination of adolescent girls by their mothers in Eldoret. It provides insights to the mothers in Eldoret's perspectives on whether cervical cancer is preventable and or curable. The introduction of HPV vaccination as a measure to combat cervical cancer in women is well commended but has involved a lot of concern and research. This HPV vaccination essentially targets adolescent girls classed as minors that need parental consent for vaccine administration. The parental awareness, attitude, intention and acceptance of HPV vaccination for their daughters have become relevant for the success of the cervical cancer preventive program. This study found a high level (85.0%) of cervical cancer awareness but much lower awareness of HPV (60.0%) and HPV vaccine 62.0%). Our results were similar to a study done in Kenya by health workers which found out that the level of awareness of cervical cancer to be 91% and 62.7% awareness of HPV vaccine .0%. Our .et al. 2012 on Parental knowledge, Attitudes, and Behaviours towards HPV Vaccination for their Children, an average of 74.0% of responders knew the relationship between cervical cancer and HPV, only 20.0% of this respondents population identified HPV as a risk factor for cervical cancer [et al.(2012), the awareness of HPV vaccine in our study was higher than that of the study in review of [Being a health worker was one of the main reasons that exposed them to the health information, which explains the higher awareness. While in research conducted by Trim l cancer . Althougeview of , but waseview of , 20.Majority of the respondents (70.0%) tertiary education, this was in conflict with the results from other studies which found no relationship between level of education and Parental knowledge, Attitudes, and Behaviours towards HPV Vaccination (ibid). However a study in Thailand on maternal acceptance, attitude and knowledge on human papilloma virus vaccination of daughters reported that the basic knowledge of HPV was found to be higher in those that had higher education this results are corresponding to our results which found out that the knowledge of HPV to be higher among the respondents who had achieved post primary education . Two hunet al. 2012 and Dahlstrom et al. 2009 on Attitudes to HPV vaccination among parents of children aged 12-15 years a population-based survey in Sweden [A study on barriers to HPV immunization for African American adolescent females reported that limited knowledge of HPV connection to cervical cancer led to reduced acceptability . Our stun Sweden , 23. On This finding, thus consistent with a study done by Pinto and colleagues, which also found out that the intent to vaccinate was directly related on attitude and apparent behavioral control. Positive attitudes nevertheless do not at all times lead to lead to parents accepting their daughters to be vaccinated . This poThe fear for cervical cancer, and life experiences of cervical cancer are the predominant reasons for mothers of adolescent girls to participate in HPV vaccination. Participating in HPV vaccination in our population while lack of awareness of HPV vaccine, concern about efficacy and adverse side effects of HPV vaccine, high cost of HPV vaccine and young age of their adolescent girls were explanation given by mothers that did not vaccinate their daughters. This concurred with other studies that identified fear of side effects of vaccine, perceiving the HPV vaccine as risky and belief that vaccine is experimental, low knowledge of HPV vaccine and cervical cancer and not participating in routine cervical smear as reasons for reduced intention to vaccinate and participating in HPV vaccination for their adolescent girls , 21, 27.Even though the results of this study may have limited generalized, they provide an insight into the knowledge, attitude, desire and practice of HPV vaccination of adolescent girls and factor that determine intent and practice of HPV vaccination of adolescent girls by their mothers in Eldoret from the parental perspective. We conclude that the awareness of HPV and HPV vaccine for prevention of cervical cancer is still suboptimal among mothers of adolescent daughters in our environment. There was predominantly positive attitude towards the use of HPV vaccination for prevention of cervical cancer among respondents; hence the high rate of desire by mothers to vaccinate their daughters. The practice of the HPV vaccination by mothers of adolescent girls was still low. There is need for increased awareness creation by government agencies and caring physicians. The government departments responsible for routine immunization should latch on this positive attitude by mothers to increase uptake by making HPV vaccination part of routine immunization for the adolescent. There is need for policy to guide and unify various stake holder efforts in the struggle against an increasing cervical cancer burden. On the other hand the policy will also save as a legal framework for service users, NGOs and activists to base their arguments on, when advocating for more financial and technical support from government and its partners that are playing different roles in combating cervical cancer in Kenya.Cervical cancer though preventable is a leading cause of mortality worldwide;Human papillomavirus is the main cause of cervical cancer and is preventable through vaccination.This study provides an insight into the knowledge, attitude, desire and practice of HPV vaccination of adolescent girls;The study also shows the factors that determine intent and practice of HPV vaccination of adolescent girls by their mothers from the parental perspective.


Recently, reanalysis of The Cancer Genome Atlas study demonstrated that human papillomavirus (HPV) genotypes in head and neck cancers other than HPV-16 have inferior survival to HPV-16-positive tumors. We aimed to examine the association of HPV subtypes and survival in a large cohort of patient samples from our institution.  Fresh frozen primary site biopsy samples were collected either in clinic or at the time of surgery. Patient demographic, staging, and survival data were also collected. Tumors were tested for HPV subtypes by quantitative polymerase chain reaction (qPCR). Univariable and multivariable analyses were performed using Cox proportional hazards regression. p=0.009) and progression-free survival . Similarly improved 5-year OS and PFS were observed for patients with HPV-positive versus negative disease . Patients with HPV-16 compared to other HPV diseases had worse 5-year OS and PFS .  280 patient biopsy samples were collected between 2011 and 2017. Mean ± standard deviation (SD) age was 61.9 ± 11.1 years and most patients (78%) were male. The majority of cancers were of the oral cavity (60%) or oropharynx (25%) and 30% had HPV-positive disease. Median follow-up was 3.76 years and 96/280 patients (34%) developed recurrences. Patients with p16-positive versus negative disease had significantly improved 5-year overall survival (OS, 77.6% vs. 53.3%;  In contrast to the data derived from The Cancer Genome Atlas, patients with HPV-16 tumors trended towards decreased PFS and OS compared with tumors driven by other HPV genotypes. Further larger multi-institutional studies are necessary to understand the relationship between other HPV genotypes and survival in head and neck squamous cell carcinomas. There has been a dramatic rise in a subset of head and neck squamous cell carcinomas (HNSCC) due to increasing rates of oral infection with human papillomavirus (HPV) leading to HPV-associated head and neck cancers , 2. Althp16-positive oropharyngeal squamous cell carcinomas (OPSCC) treated with radiation and chemotherapy compared with approximately 40% for those with HPV-negative tumors treated with similar regimens [HPV and its surrogate marker p16 have been definitively shown to be independent prognostic biomarkers for improved survival for cancers arising within the oropharynx in the context of prospective randomized controlled trials –10. Fiveregimens , 11. Sinregimens , 12–27.n = 41,950) with established HPV status (PMID 29801040). They found that patients with HPV-positive oral, oropharyngeal, laryngeal, and hypopharyngeal tumors faired better than HPV-negative patients , oropharynx , hypopharynx , and larynx ). Unfortunately, the HPV type for each patient was not available to draw type specific conclusions.However, significant questions surrounding the role of HPV in HNSCC remain, including particularly the following: (1) whether HPV plays a prognostic role in subsites other than the oropharynx, and (2) if HPV subtypes other than type 16 have the same prognostic significance. However, there have been recent high-quality data addressing each of these questions that were previously limited by smaller datasets. In contrast with many prior studies showing no difference in outcome outside of the oropharynx, Li and colleagues utilized the US national cancer database (NCDB) data and analyzed all HNSCC patients (n = 8), 35 (n = 3), and 56 (n = 1). This analysis revealed that HPV-tumor types other than HPV-16 had inferior survival when compared to their counterparts with HPV-16-positive disease, with similar survival rates to those seen in HPV-negative HNSCC. This suggests that patients with these genotypes may be inappropriate candidates for treatment deintensification [To address the HPV type question, Bratman and colleagues reanalyzed The Cancer Genome Atlas (TCGA) cohort and utilized viral reads derived from the RNA sequencing to determine definitive HPV status and HPV type.  We note fication , 29 and The study by Bratman had strengths such as relatively large sample size and definitive HPV detection and subtyping through RNA sequencing; however, it also had weakness including lack of an independent validation cohort, imperfect TCGA survival data , and theth edition), treatment regimen, and posttreatment follow-up information. P16 testing was performed on formalin fixed samples for the majority of patients (59/70) with oropharyngeal cancer primaries and a subset of other cases (27/210) as part of routine clinical care.Patients with head and neck squamous cell cancer set to undergo treatment with curative intent (with either primary radiation or primary surgery) were prospectively enrolled through the head and neck cancer clinic at London Health Sciences Centre. Patients with distant metastatic disease, treated with palliative intent, with known recurrence prior to biopsy sampling, or with missing HPV testing data were excluded. Clinical data was collected, including age at diagnosis, use of tobacco and alcohol, AJCC TNM staging .E7 regions of HPV −16, −18, −33, −35, and −56. We also included HPV type 18 in our analysis as we have previously identified its presence in head and neck cancer samples [In an effort to screen clinical samples for the presence of human papillomavirus (HPV), we designed a multiplex quantitative PCR to identify those samples that were HPV-positive and to confirm the HPV type in the positive samples. Tumor genomic DNA (gDNA) samples were screened with primer sets designed using MacVector Ver.15 software (Primer3) to amplify small stretches within the E6/ samples  despite  samples , 30 We dμl) were prepared using the QuantiTect multiplex PCR no ROX kit (QIAGEN) with 0.2 μl of template gDNA. A Stratagene Mx3000P was used for performing qPCR with the following conditions: one cycle of heat inactivation/enzyme activation at 95°C for 15 min, 40 cycles of denaturation at 94°C for 60 seconds, and annealing/extension at 60°C for 90 seconds.qPCR reactions  was used to determine the baseline for each probe to determine threshold cycle (Ct) values. Samples with GAPDH Ct ≥ 35 indicated poor gDNA yield. Signals for any fluorescent dye greater than Ct ≥ 35 were considered questionable and were repeated before an evaluation was made.p values <0.05 were incorporated into a multivariable regression model and sequentially removed using backward elimination techniques until all remaining covariates had p values <0.05. All statistical analysis was performed using SAS version 9.4 software  using two-sided statistical testing at the 0.05 significance level.Descriptive statistics were generated for all patients and stratified by HPV status , compared using the Chi-square test or Fisher's Exact test, analysis of variance (ANOVA), or Kruskal–Wallis test as appropriate. Overall survival was calculated as the time from date of consult to date of last follow-up and/or death (any cause), whichever comes first. Progression-free survival was calculated as the time from date of consult to date of last follow-up and/or recurrence and/or death (any cause), whichever comes first. The Kaplan–Meier estimates were generated for OS and PFS for all patients, patients receiving primary surgical treatment  and patients with oropharyngeal cancer only, stratified by HPV and p16 status and compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression was performed on all patients to identify significant predictors of OS and PFS. All eligible variables with univariable Between 2011 and 2017, biopsy samples from 280 patients with HNSCC meeting our inclusion criteria were obtained. Baseline patient and tumor characteristics are shown in p=0.034) and less likely to have T4 disease (p=0.113), perineural invasion (p=0.071), and extranodal extension (p=0.171). HPV-16-positive patients received more nonsurgical treatment (p < 0.001) and less adjuvant treatment (p < 0.001) compared to HPV-negative and other HPV patients. In addition, HPV-16-positive and other HPV patients were more likely to have oropharyngeal primaries compared to HPV-negative patients  and less likely to have oral cavity primaries .Compared to their HPV-negative counterparts, HPV-16 and other HPV-positive patients tended to be younger ; however, this was not significant . This remained not significant for both OS and PFS after incorporating HPV-negative patients . In contrast, patients with p16-positive disease had significantly better 5-year OS and PFS compared to patients with p16-negative/p16 unknown disease . Ninety-two patients (32.9%) were deceased and 96 patients (34.3%) had developed recurrences. Five-year OS and PFS for all patients were 57.9% and 46.3%, respectively. Compared to HPV-negative patients, HPV-positive patients had improved 5-year OS and PFS , alcohol abuse , T4 versus T1-T2 disease , N2-N3 versus N0 disease , stage IV versus stages I-II disease , perineural invasion , extranodal extension , and lymphovascular invasion  as significant predictors of worse OS. p16-positive disease was significantly predictive of better OS . Stage IV versus stages I-II disease  and perineural invasion  remained significantly predictive of worse OS from the multivariable analysis.Results from univariable and multivariable Cox proportional hazards regression models are shown in p=0.011), N2-N3 versus N0 disease , perineural invasion , extranodal extension , lymphovascular invasion , and receiving neoadjuvant treatment  as significant predictors of inferior PFS. p16-positive disease was significantly predictive of improved PFS . From the multivariable analysis, T4 versus T1-T2 disease , N2-N3 versus N0 disease , perineural invasion  and receiving neoadjuvant treatment  remained significantly predictive of worse PFS.Similarly for PFS, univariable analysis identified T4 versus T1-T2 disease , both not significant. HPV-16-positive patients compared to other HPV disease had worse 5-year OS and significantly worse 5-year PFS ; however, this was not significant after incorporating HPV-negative patients . Although patients with p16-positive disease had improved 5-year OS and PFS compared to patients with p16-negative/unknown disease, this was no longer significant .Two hundred and three patients received primary surgical treatment . Compared to the initial cohort of 280 patients, these patients were more likely to have oral cavity cancer (79.8% vs. 60.4%), to have received adjuvant treatment (71.4% vs. 52.5%), and less likely to be HPV-positive (19.7% vs. 30.0%), HPV-16-positive (16.3% vs. 26.8%), and p16-positive (6.4% vs. 17.9%). Similarly compared to HPV-negative patients, HPV-positive patients had improved 5-year OS but similar 5-year PFS . Patients with p16-positive disease compared to p16-negative disease had significantly improved 5-year OS and PFS .Some studies have suggested that the improved survival associated with positive HPV status is not present for carcinomas in subsites other than the oropharynx . For thiThe literature contains limited data regarding the prognostic implications of viral genotypes on oncologic control and survival. There are nearly 200 currently recognized genotypes of HPV, with several high-risk genotypes considered causative agents in OPSCC. These include HPV −16, −18, −33, −45, −52, and −58 . We inveIn contrast to the study by Bratman and colleagues, patients with HPV-16 disease did not experience superior survival to patients with disease due to other HPV genotypes. Rather, patients with disease due to the other type  appeared to fair better with a trend towards improved progression-free survival . PatientOur data support previous literature that p16 expression is strongly associated with improved survival, including sites other than the oropharynx . The pron = 9).Recent studies have suggested treatment deintensification for HPV-associated head and neck cancers as a promising therapeutic strategy with similar efficacy with decreased toxicity , 40–44. We suggest larger multi-institutional studies to determine the impact of HPV genotypes on patients with head and neck squamous cell carcinomas. Although HPV genotyping is not widely implemented in head and neck cancers, we believe that HPV genotyping should be routine in the management of HPV-positive head and neck cancers in the future. Our ability to risk stratify can be refined with the use of other potential adjunctive biomarkers to better assist physicians in selecting appropriate patients for deintensification. Future deintensification protocols should consider the pattern of relapse for the type of HPV-positive cancer. Patients with genotypes who have inferior survival rates comparable to those of HPV-negative head and neck cancers would then be excluded from consideration of treatment deintensification.Although our patient data collection and tumor collection were prospective, there were limitations to our study. Our cohort involved a variety of tumor sites treated with heterogeneous regimens that could potentially obscure important findings. In addition, the number of tumors with other HPV genotypes was relatively small, which may limit the ability to detect significant differences. Given the rarity of other HPV types, large multi-institutional institutional efforts are likely needed to have sufficient power to conclusively answer this question.To the best of our knowledge, this study is the first attempt to validate the findings by Bratman and colleagues on the prognostic significance of HPV genotypes in head and neck cancers. In contrast to their findings, patients with HPV-types other than 16 trended towards improved progression-free survival compared with HPV-16 related disease. Large, multi-institutional efforts are needed to conclusively determine the correlation of HPV type and survival in HNSCC.