Following a successful Human Papilloma Virus (HPV) vaccination pilot in 2013–2015 in Kitui county, Kenya introduced the HPV vaccine in October 2019 with a goal to immunize approximately 800,000 girls annually against HPV. Our study assessed the knowledge, attitudes, and practice of affected groups towards HPV infection and vaccination in two counties of Kenya. Semi-structured interviews from children aged between nine and thirteen years and key informants comprising of parents, head teachers, community leaders and health workers involved in HPV vaccination in health facilities from Mombasa and Tana-River counties were conducted. Content was analyzed thematically and coded for emerging themes using the QRS Nvivo 12 Plus  software package. From our findings, a significant proportion of participants, especially children, have limited knowledge of the subject. Vaccination of boys was opposed by most participants. Parents and the community members are not in favor of HPV vaccination, as compared to the other groups. A similar pattern of inadequate knowledge and strongly opposed attitudes was observed in Tana-River and Mombasa. Active community involvement in primary prevention strategies may promote the uptake of the vaccine which can be achieved by robust awareness, modifying the negative beliefs about HPV vaccine and encouraging the perceptibility of HPV vaccination. Human Papilloma Viruses (HPVs) are a group of sexually transmitted viruses that are implicated to cause cervical cancer . EvidencModelling projections suggest that high HPV vaccination coverage among girls in low-and middle-income countries (LMICs) can lead to cervical cancer elimination. Thus, the introduction of HPV vaccination is of especially urgent need in developing countries where there is a high burden of cervical cancer ,17,18,19Globally, the burden of cervical cancer is greatest in developing countries, including the Eastern Africa countries. In terms of cancer incidence in Kenya, cervical cancer is second only to breast cancer, with 5250 (11%) new cases per year in both men and women . In KenyGlobally, HPV vaccines were rolled out in 2006 with many countries showing a tremendous scale up by adopting the HPV vaccine in their national immunization schedules ,26. FollStudies in routine vaccination with three doses of HPV vaccine have been recommended for adolescent girls and boys at 11 or 12 years of age. However, vaccine uptake remains suboptimal globally. This has been associated with low levels of vaccine awareness ,33,34. TGenerally, the perception of the communities in Kenya in regards to HPV vaccination revolve around perceived mistrust towards new vaccinations, insufficient knowledge about HPV infections and HPV vaccination, and high levels of misinformation due to inadequate top down training of stakeholders ,37,38,40Our understanding of the views on HPV vaccination in Kenya is fragmented, little is known about HPV vaccine uptake in different parts of the country, and moreover, the attitudes of stakeholders towards vaccinating boys are not known at all. In this regard, our research work seeks to bring an insight on the status of the HPV vaccination program and perceptions about the introduction of HPV vaccination to the 10 to 11-year-old boys and girls in the coastal region of Kenya .The objectives of this study were twofold: (1) to assess the knowledge and attitude of HPV vaccination among school boys and girls, parents and other key informants comprising of head teachers, health workers and community leaders regarding HPV vaccination, and (2) to gain information about the practice of HPV vaccination programs in Mombasa and Tana-River counties in Kenya and potential improvements.The interviews took place in two counties, Mombasa and Tana-River, located on the Indian Ocean coast, where no similar survey has been conducted before. The two counties are characterized by a different socio-economic situation, which allows comparison of the results from urban settings (Mombasa County) and rural settings (Tana-River). Mombasa county has one of the highest Per Capita Gross County Product (GCP) of 271,039 Kenya shillings in 2013–2017 . The GCPIn this descriptive qualitative study, individual interview participants were purposively selected using a maximum variation sampling strategy, with the inclusion criteria of having at least a boy or a girl aged between 9–13 years, parent, head teacher, community leader and health worker related to HPV vaccination in both Mombasa and Tana-River counties. The interviewees were drawn from different population categories of economic class, gender, age, place of residence and religion. From both counties, we managed to interview 7 school boys and 19 school girls aged between 10–13 years all from different schools. Among the key informants, interviews were conducted from 10 parents, 23 head teachers, and 22 community leaders who comprised of chiefs, village elders, religious leaders and community health volunteers. The 21 health workers comprising of nurses and public health workers had been involved in HPV vaccination in health facilities. After transcription of interviews participants were assigned numbers randomly to preserve their anonymity.Data collection was conducted through semi-structured interviews of which the guide was drafted focusing on three broad themes: for participants’ knowledge related to cervical cancer, their attitude towards cervical cancer prevention and their views on possible ways to address the barriers in current practice, see the topics in the The audio files were transcribed verbatim. The original list of codes was based on research questions and literature review. Content was analyzed thematically, indexed, and coded inductively for emerging similar themes using the QRS Nvivo 12 Plus software package  for content analysis of unstructured qualitative data. The initial open codes were sorted into sub-themes based on their similarity. These subthemes were clustered and refined to form broad themes and debated in the research group. The knowledge nodes responses, based on current evidenced based knowledge, were categorized into three according to the accuracy of the response as correct, lack of an answer or severe misunderstanding. Under attitude nodes, the opinion of others was classified depending on the nature of the attitude as supportive, opposing or neutral. Data collection, analysis, and reporting followed the Standards for Reporting Qualitative Research (SPQR) guideline see  46]..46].n = 10) was structured to include a similar proportion of interviews from each county and each stakeholder group. Once satisfactory reliability was established, DN then proceeded to code the remaining data independently [We ensured consistency during protocol preparation, data collection, development of a coding system, interrater reliability, and data analysis by following Guba and Lincoln’s criteria for determining rigor in qualitative research ,47. Two endently . Cohen pPermission to conduct the research was granted by the University of Eastern Africa, Baraton (UEAB) Research and Ethics Board in Kenya and a research permit from National Commission for Science, Technology and Innovation (NACOSTI) License number NACOSTI/P/20/6514. Written informed consent was granted by all the adult participants prior to the interview and on behalf of the minors, the parents and teachers signed the informed consent, see Women dominated our sample, with 53 of the 76 adults interviewed being women. Among the 10 parents interviewed 9 were female, additionally, in other adults’ groups like the nurses in the health worker’s group consisted of females, exclusively. The age of parents, health workers and nurses ranged from 30–45 years, while the age of community health workers ranged from 35–60 years. The boys and girls ages ranged between 10 and 13 years.The burden of cervical cancer was assessed among the health workers and community leaders. The responses were consistent and emphasized that late diagnosis was rampant and the rate of mortality from cervical cancer is quite high. As participant 32, a health worker noted“...Yes, cervical cancer is a real problem in my community. We have had cases of several women who get diagnosed at very late stages and end up losing their life and practically we lost one of the community health volunteers to cervical cancer because it was diagnosed at a very late stage”.Additionally, an upsurge in the frequency of positives tests during cervical cancer screening was reported by participant 57“...Yeah it is, well of late we are getting cases because we have been encouraging people to do cervical cancer screening, and I think we got some few cases, so cervical cancer it is real in our community”.The burden of disease was not only observed by health workers, for example participant 19, a head teacher said that,“...Yes, it is rampant. So many people die with cervical cancer”.Participant 35, a community leader expressed that,“...It is a very serious problem, because, in the past, we did not understand the disease, but this time, we have seen women; it has become very challenging, because many are suffering from the disease. Before it is known, the mother loses her life, she dies“.The knowledge theme had seven nodes comprising of answers related to knowledge about HPV, goal of HPV vaccination, prevention of cervical cancer and HPV, risk of catching HPV or cervical cancer, what is cervical cancer, what is the cervix, and what is the goal of Pap smear. The answers were classified according to their correctness .Most responses by healthcare workers were correct while the highest percentage of incorrect or no responses were by children. The lack of appropriate biological knowledge was particularly noticeable for children see . The resConsiderable numbers of responses with serious misunderstanding were found, such as 37% of head teachers when asked what HPV is, 26% of community leaders when asked what the HPV vaccine is for, and 57% of children when asked what cervical cancer is. This is echoed by the quote by participant 23, a head teacher on the importance of HPV vaccination,“…I don’t think it’s important at this point because I have never heard of a young child having the cervical cancer or something”.Another participant 40 who was a parent felt that,“…if she received this vaccine, even if she goes to get married, if she meets the man who is infected with the HPV virus, they do not get it. She will be safe”.The responses on how to prevent HPV and cervical cancer were acceptable in most groups, with the health workers and community leaders having 99% and 74%, respectively. However, others demonstrated no or limited knowledge on the prevention of cervical cancer and HPV. Participant 11, a community leader said,“…I can’t tell the prevention because I don’t know what is cervical cancer”.A parent had the feeling that,“…Preventing will be by giving medicine, try to prevent it by giving medicine that will prevent it from happening”.Severe misunderstanding was displayed on the prevention of HPV and cervical cancer by participant 1, a community leader,“…prevention mmmmmh mainly this disease we can prevent by your lifestyle maybe. The food you eat, that is your lifestyle”.While the answers to the question on knowledge of the risk of HPV and cervical cancer were adequate in all groups, many participants had difficulty in answering the question on what HPV is. Some said they had only heard about human immunodeficiency virus (HIV) and not HPV; participant 31, a health worker uttered,“…All I know is the one that is associated with HIV”.An answer by participant 23 showed a severe misunderstanding,“… acidic food actually, kind of thinking is a bit, delays it to the feelings of papilloma because once you eat this thing you feel some changes and then you relate it to papilloma”.Most adult participants gave a correct answer to the question what is cervical cancer. Some were shy and chose to stay silent and not respond, especially in the children’s (78%) and head teachers’ (19%) group. A boy said that,“…I have heard it is a terrible disease that is killing people”.Participant 56, a head teacher said,“…Yeah, you know I don’t have knowledge of health, otherwise I have heard about it”.The level of knowledge about the purpose of the Pap smear was moderate among the three groups asked, with parents (66%), head teachers (63%) and community leaders (30%) having a reasonable level of knowledge and giving a correct answer. This question on cervix was asked to all the groups except the health workers. A considerable portion of the community leaders (61%) gave a correct response then the head teachers (43%), parents (36%) and the children (20%). The children’s group responded most silently (78%).The attitude theme had six nodes which were access to information, efficacy, safety, opinion of others, cultural beliefs, and religious beliefs. With the exception of the opinion of others, these child nodes were linked to the attitudes and perceptions of individual participants. The opinion of others meant how the interviewee thought other people  felt about HPV vaccination. The opinions of others were categorized depending on the nature of the attitude .In regards to acceptance of the HPV vaccination, perception, and willingness to participate in the HPV vaccination exercise, the participants noted that challenging access to and inadequate availability of information as a factor influencing attitude. Participant 42, a community leader reported that the community lacked information,“…they still need to be educated because the information they have is still low”.n = 11) was also mentioned as a barrier to the uptake of the HPV vaccine.Low literacy (n = 13). A parent had this to say,Only a handful of the participants alluded to the efficacy of the HPV vaccine. A few did not have confidence in its ability to prevent cervical cancer  believed that the HPV vaccine could be ineffective in boys because they do not have a cervix. This view is depicted in a quote by participant 20, a head teacher,Quite a number of participants  was mentioned frequently by the participants. Participant 31, a health worker, articulated their fears,The fear of unknown  . This coAlthough knowledge gaps among health workers were evident, our findings proved the availability of information, to some extent. Information available in the community is derived mainly from seminars and workshops arranged by health authorities. Apparently, the information given to girls and parents prior to vaccination was suboptimal . Thus, aMisinformation about HPV vaccination is common among community members and has influenced attitudes towards HPV vaccination uptake. A majority of the participants insinuated that the HPV vaccine was a birth control method and it is alleged that it is laced with family planning components to sterilize the girls. Others even went to the extent to report that the HPV vaccine itself was an introduction of cervical cancer to the girls. This was further complicated by the fact that some religious leaders were sources of these statements as these arguments were already reported by Otieno et al. ,55. MisiA variety of reasons were given by participants for not vaccinating children in their communities, including irrational fear of unknown vaccines, deviation from cultural and traditional norms, pressure from community members, husbands barring their wives from vaccinating the girls, and absurd beliefs such as vaccination being an initiation into the Illuminati. Findings from our study confirm that cultural norms and religious factors have shaped the HPV vaccination landscape ,57. MostNot unexpectedly, safety concerns have been raised about the effectiveness of the HPV vaccine. Some reported that they had fear of the side effects or their children dying, the girls also expressed fear of being injected. However, there is no evidence of association of HPV vaccine and adverse effects  and HPV There were disparate responses to the question on whether to vaccinate boys or not. One of the boys expressed a desire to also be immunized and this agrees with Grandahl et al. findings on “I also want to be vaccinated!” where the boys were in favor for the HPV vaccine . Most paThe opposing attitude from the community and parents was quite conspicuous from both counties. The disapproval has been observed in other studies where community groups and parents have had controversy and opposed the HPV vaccination due to their irrational fears, concerns, and arguments. Active involvement of the health workers in dialogues to address the parents’ and community’s concerns is a definite way to mitigate this ,63. CapaThe parents and children were involved in the consent process. From our findings, the adolescent girls exercised high level of autonomy as demonstrated by the nurses’ response to the question on how the adolescent girls felt about being vaccinated. This is in line with a study conducted in South Africa on factors influencing vaccine uptake. However, in this study, the nurses did not express any difficulty initiating these conversations about sex with the adolescents. This contradicts with our findings on the role of the health care workers on the difficulty in initiating conversations about sex with the adolescents .The COVID-19 pandemic was seen to have affected the practice of HPV vaccination exercise. The safety and efficacy concerns towards the COVID-19 vaccine observed across countries and suspension of preventive activities greatly influenced the uptake of HPV vaccination ,65. It wFrom the health workers, it was revealed that the HPV vaccine has yet not been included in the national immunization schedule. They recommended that it should be added as this would curb the failure and forgetfulness to go for the second doses. Evidence from literature shows that countries will have to increase their national immunization budgets due to the inclusion of the HPV vaccination to the routine immunizations . CommuniThis study reveals the ailing obstacles to the HPV vaccination uptake from two counties in Kenya. Similar results for the two counties might be generalized to the country, as the Kenyan population is not as diverse and the majority of residents live in urban settings. The uniform recommendations from a portion of the participants, especially the health workers and community leaders on sensitization and community involvement from both counties demonstrates a willingness to promote HPV vaccination if efforts are concerted.The interviews were conducted in only two counties in Kenya, which is considered a shortcoming of our study. For our data collection, we used semi-structured, face-to-face interviews, which ensures a high degree of content validity as we collect first-hand detailed information on the subject. Selection bias is inherent in this methodology, and certainly affects this work. Selection bias can affect the interpretation of the data.The study adds to the existing knowledge on the impact of low HPV vaccination uptake in Kenya. Involving the community in primary prevention strategies may promote vaccine uptake. This can be achieved by raising awareness, changing negative beliefs about the HPV vaccine, and promoting HPV vaccine perceptibility. The personal presence of experts helps to spread knowledge about cervical cancer, HPV infection, and HPV vaccination. Considering the introduction of uniform methods for tracking HPV, vaccination programs will improve HPV vaccination coverage and influence policy making. A grassroots social mobilization is needed to improve the willingness of the population to vaccinate, with accurate information for parents and teachers, who are key implementers and promoters of HPV vaccination (yet often do not support vaccination). In addition, a campaign to reach children is critical; although they cannot decide on their own, our results demonstrate that parents in Kenya take their concerns into account. Future studies should focus on mass awareness and education about HPV vaccination and cervical cancer, as well as efficacy of innovative ways and tactics to deliver messages to the community.


For more than a decade human papillomavirus (HPV) vaccine have been implemented in most high-income countries, and more recently also in several low- and middle-income countries. The vaccines are safe and their impact and effectiveness in preventing HPV vaccine type infection and associated diseases has been thoroughly established. Currently, the primary recommended cohorts for immunisation are adolescents, 9–15 years of age but HPV is an ubiquitous infection that is mainly (but not exclusively) sexually transmitted. Sexually active adults remain susceptible to infection and continued transmission of the virus, representing a reservoir of infection in the population. A recent meeting, conducted by the HPV Prevention and Control Board (HPV-PCB), reviewed the current status of HPV vaccination of adults, discussed limitations, challenges and benefits of HPV vaccination of adults, evaluated the effectiveness of HPV vaccination after treatment of post cervical cancer and precancerous lesions, and discussed the potential impact of adult vaccination on cervical cancer elimination strategies in light of the current and future HPV vaccine shortage. HPV-PCB is an independent multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV prevention and control programs. The HPV-PCB concluded that, given the current data available on adult HPV vaccination and the ongoing vaccine supply constraints, it is too early to implement routine vaccination of adults. Many research gaps need to be filled before we have a better understanding of the efficacy and broader public health impact of HPV vaccination in adult women. ThThe direct assessment of the time lag between HPV infection acquisition and cervical cancer occurrence is unethical. The uncertainty about the time lag may affect the validity of the cervical cancer risk estimates and of the expected impact of preventive measures.Therefore, an attempt was made to estimate cervical cancer incidence rates in hr-HPV-positive women as a function of the time lag between a hr-HPV prevalence measurement (exposure) and cervical cancer detection (outcome). Based on this analysis, it may be possible to make longitudinal and cohort-specific projections of cervical cancer incidence from age-specific hr-HPV prevalence data. An additive Poisson regression model without an intercept term was used to comply with the restriction that cervical cancer rates should be zero if the HPV prevalence is zero. Using the average age at sexual debut, by birth cohort and by location, cervical cancer incidence projections could be made. These projections flattened from age 35 onwards. Moreover, the impact of the mean age at sexual debut was strongest in younger age groups.The effect of hr-HPV prevalence on annual cervical cancer incidence among HPV+ women increased with the age at HPV detection and the time lag between hr-HPV prevalence and cancer incidence assessment. Furthermore, below age 35, cervical cancer risk changed based on the average age at first sexual encounter, which is a proxy for the HPV infection duration. Both findings are consistent with the current biological model of HPV progression to cervical cancer. This allows short-term predictions of the annual cancer incidence from HPV prevalence data (which are relatively easy to collect) in countries without cancer registration.The United States Food and Drug Administration (FDA) approved expanding the age indication for the 9-valent HPV vaccine to age 45 in October 2018. Therefore, there is a need to perform cost-effectiveness analyses of middle-aged adult vaccination, more specifically, the cost-effectiveness of HPV vaccination for females  between ages 27 and 45. Five models were used to inform adult HPV vaccination policy decisions in the US: the HPV-ADVISE model ; a simplified model (CDC); the Merck model; the Harvard model; and the Policy1-Cervix model . All five models include a wide range of health outcomes , all account for herd effects and examine a long time period (~ 100 years).However, the models differ in structure, calibration, cervical cancer screening assumptions,vaccine uptake assumptions for middle-aged adults, the natural history of HPV parameters, HPV transmission dynamics, and cost and quality of life assumptions.Routine vaccination at ages 11 or 12 years with catch-up vaccination through age 26 years for females and age 21 years for males was shown to be cost-effective in all models, ranging from cost savings in the HPV-ADVISE model to $34,600 per quality-adjusted life year (QALY) gained versus no vaccination in the Harvard model. In June 2019, the Advisory Committee on Immunization Practices recommended to extend catch-up vaccination for males through age 26 year, making it the same as the existing recommendation for women.The vaccination of adults up to the age of 45 would prevent an additional 56,000 cases of CIN2/3 compared to the 13,000,000 cases prevented by the current recommendation (0.43%). Similarly, an additional 3000 cases of cervical cancer compared to the 653,000 cases prevented by the current recommendation (0.46%); an additional 124,000 cases of anogenital warts compared to the 32,000,000 cases prevented by the current recommendation (0.39%); and an additional 4000 cases of other HPV-related cancers compared to the 769,000 cases prevented by the current recommendation (0.52%)  2014 Roadmap provided a descriptive overview of five heterosexual couple-based longitudinal studies in its discourse of HPV transmission rates, suggesting greater rates of female-to-male (F-M) than male-to-female (M-F) transmission. A systematic review and meta-analysis were performed to assess the evidence for the differential transmission rate hypothesis in couple-based studies in regard to genital-to-genital HPV transmission . Seven l2 = 75%). Excluding two potential outliers did not alter the rates significantly; F-M transmission was still favoured. However, these findings must be interpreted with caution due to the presence of substantial statistical heterogeneity.The overall rate difference was 0.61 infections per 100 person-months (95% CI -0.27-1.49), indicating that F-M transmission is higher, although the result was not significant, and substantial statistical heterogeneity existed  in Amsterdam, the Netherlands, showed that the vaginal and anal hr-HPV prevalence were 46 and 55%, respectively, whereas anti-HPV seropositivity, against a least one of the high risk types included in the Gardasil 9 vaccine, was 37% . This leThere are several reasons to offer HPV vaccinations to SWs : SWs areAlthough HPV vaccination should be offered to all girls prior to sexual debut, studies are needed to directly or indirectly establish the effectiveness of vaccinating SWs. Although RCTs generally provide the best answer, these are not realistic in the current setting. Because vaccines are safe, a benefit/risk balance is not needed, and a cost-benefit balance will suffice.n = 1209) and after (n = 1235) the introduction of the program. This showed a slight and non-significant increase in HPV-6/11 types 6 and 11 and a significant decrease in HPV-16/18 types 16 and 18 from 37.9 to 31.8% (odds ratio (OR) 0.76, p = 0.0014). Although it is an indication of an early vaccine effect, confirmation will be necessary. Moreover, further work is underway to link the vaccine status to genital wart treatment prescribing data, HPV prevalence data, and, in the long term, HPV-associated cancers.As MSM are at a high risk of HPV infection and associated disease and have little to no benefit from the girls-only vaccination programme, a vaccination programme was recommended for MSM attending sexual health clinics in Scotland . The proThere is large global variability in cervical cancer incidence rates, with exceptionally high rates in the African region. However, even in regions with high incidence rates, exceptions exist, such as La Reunion in Eastern Africa and Niger in Western Africa, showing rates of approximately 10/100,000 women, which is well below the rates in some countries in northern, southern and eastern Europe Fig. .Fig. 3VThree HPV models, the Policy 1 model, the Harvard model and the HPV-ADVISE model, as well as an HIV model, the Spectrum model, were selected, as they are dynamic models that include vaccination, screening and treatment. These models were used to investigate three scenarios. Scenario 1 is based on girls-only vaccination, with no change in screening compared to the current situation. Scenario 2 is based on girls-only vaccination, with once-in-a-lifetime screening at 35 years of age. Scenario 3 is based on girls-only vaccination, with two lifetime screens at 35 and 45 years of age. All scenarios are based on HPV-based screening, 100% treatment efficacy, 10% loss to follow-up for screening and 90% coverage of 9 to 14-year olds, the lifelong duration of immunity, and 100% efficacy for 7 h-HPV types for the vaccine. While all scenarios indicated that low-income countries (LICs) will go below the 10/100,000 threshold, the 4/100,000 threshold was only reliably reached by scenario 3.Looking at the cervical cancer incidence, the addition of boys to the vaccination programme has shown little impact in India, Vietnam and Nigeria and some impact in Uganda, while catch-up vaccination up to the age of 25 has had no impact in any of these four countries.These data have led to the development of a global strategy directed towards the elimination of cervical cancer, aiming for all countries to get below the incidence level of 4 cases/100,000 women. The 2030 targets set to achieve this goal are as follows: 90% of girls fully vaccinated at the age of 15; 70% of women screened with a high-precision HPV-based test at the ages of 35 and 45; and treatment and care for 90% of women with identified cervical disease.Although 50% of all countries in the world have introduced the HPV vaccine, this only covers approximately 30% of all girls globally. Furthermore, while 86% of HIC and 58% of upper-middle-income countries (MICs) are covered, only 33% of lower MICs and 16% of LICs are covered, which are the countries where the burden is the highest.> 15 years) and multi-age cohort HPV vaccination strategies until all countries have access to the HPV vaccine. This will significantly relieve supply constraints in the short term and enable the allocation of doses to high-burden countries currently planning to introduce this vaccine. It is important to note that the above estimates were made prior to the coronavirus pandemic and so could not consider any reduction in vaccine uptake that might have resulted from interruptions in school and clinic-based programs.There is an insufficient vaccine supply to meet the overall demand of the Global Alliance for Vaccines and Immunisation (GAVI) countries, although all planned GAVI-supported HPV vaccine introductions are moving ahead with routine cohorts, without room for multi-age cohorts (catch-up). At least one MIC had to postpone introduction in 2019 due to the lack of supply. The supplies are expected to slowly grow over the next 1–3 years, followed by quicker growth in the mid- to long-term. Several scenarios have been used to compare dose requirements, including a 2-dose and a 1-dose schedule, with or without catch-up vaccination, and extended schedules with the second dose after 3 or 5 years. At a base supply level, all scenarios experience a shortage in the short term, with the 3-year extended interval being least affected, but supplies will be adequate in the mid- to long-term time period. However, in the case of low supply, only 1-dose schedules will have adequate supplies in the mid- to long-term, with the 3-year extended interval as a possible alternative. The introduction of catch-up programmes, including the vaccination of adults, may lead to postponed introductions in 1–27 countries in the short term, leaving 45,000–143,000 girls/women vulnerable to cervical cancer. Some HICs have already introduced gender-neutral vaccination, which requires 9 million (M) doses or 18% of the global demand. If other HICs add boys to the programme, this will require another 4 million doses, which might mean that introduction is delayed in 12 LMICs. This led to the Strategic Advisory Group of Experts on Immunization (SAGE) recommendation that countries should temporarily postpone the implementation of gender-neutral, older-age group  is re-opening its vaccine-producing factory, and the Innovax bivalent vaccine has now been licensed in China. While important, these developments would not be enough to solve the immediate problem of shortages. The shortage is foreseen to be resolved by 2023/2024.Intradermal immunization may be an alternative strategy to evaluate. It has been done for influenza at 1/10th of the dose. This solution has also been contemplated for polio and rabies vaccines. In some regions, e.g., eastern Europe, intradermal delivery is already quite common. However, proper intradermal delivery is more difficult, and switching from intramuscular to intradermal delivery will take time and requires effort.Older cohorts can be vaccinated for different purposes: 1) to benefit the community by reducing transmission or healthcare costs; 2) to benefit the individual, although the latter might be limited in older cohorts based on the studies reviewed during the meeting.If vaccinating entire older cohorts is not possible considering the higher costs or shortage of vaccine supply, the focus could be on high-risk groups, such as MSM or HIV+ women.Evidence is accumulating that the vaccination of women with CIN2+ before or after treatment reduces disease recurrence of disease. Provision of the vaccine treatment should be considered, regardless of age.Two sites are available to block HPV infection by antibodies: 1) the binding of the virus to the basement membrane and 2) the binding of the virus to L1 binding sites on keratinocytes for transport into the cell.To protect against HPV infection, low levels of antibodies may be sufficient, but maybe high avidity is necessary.Given the preventive effect of carrageenan, its use as a standard lubricant during pelvic exams should be considered. Three trials using carrageenan are currently underway; preliminary results show that it is 40% efficacious as a general use vaginal gel against incident HPV infection.The priority for HPV vaccination lies with the target groups: to achieve high coverage in girls and boys between 9 and 14 years of age first.The vaccination of boys is not just focused on cervical cancer prevention; it is also directed at several HPV-related cancers that also occur in men. For instance, in many HICs, there has been a steady increase in the number of HPV-related oropharyngeal cancers, with the HPV-related cancer burden in men approaching that in women. Furthermore, gender-neutral vaccination may be a way to increase protection against all HPV-associated cancers in countries with lower vaccination coverage in females.To date, the goals and policies for HPV vaccination have been focused on benefits for vaccinated individuals. It may be necessary to think more broadly: by blocking transmission, a rapid drop in HPV prevalence may be achieved.It may be too early to think about the elimination of cervical cancer. We should aim to increase HPV vaccination coverage in countries with the highest cervical cancer incidence first, even if formal elimination will only be possible if vaccination is combined with screening and treatment, which may be too costly for many LMICs.The impact of a pause/delay in the use of a valuable vaccine should not be underestimated. Anti-vaccine messaging can have a large negative effect on vaccine acceptance in both HICs and LMICs; therefore, these must be strongly countered.If the goal truly is to eliminate cervical cancer as a major public health problem, we need to immunize whole populations, analogous to the polio eradication effort. However, the eradication of cervical cancer may not be achieved: a rate of less than 4/100,000 women is not eradication of the cancer or the underlying HPV infections.We have to think globally, as the need for vaccines in HICs, MICs, and LICs is the same, with younger cohorts as a priority. However, we should not overlook the potential benefits such as reduced costs of screening programs it can offer in the future.Now that more data are available, revisit the efficacy of HPV vaccination in older womenInvestigate the impact of HPV vaccination on reducing transmission with tissue culture experiments, demonstrating that shed virus can be neutralized or with RCTs showing a reduced risk of transmissionDevelop more sensitive assays to detect mucosal anti-HPV antibodies and use these assays in combination with standardized sample collection to increase comparability between studiesInvestigate the risk of progress to cervical cancer development after primary HPV acquisition at different agesDevelop RCTs to investigate the collection of cytology samples in the presence or absence of carrageenanBased on large data sets, including HPV genotyping on cytology samples, after a change in sampling device: look for an effect on glandular disease before and after the new deviceIdentify a small, not previously vaccinated population, preferably on an island, and give everybody a single dose of vaccine. This should have a profound impact on transmission. At the same time, it may be possible to assess the potential for eliminationGiven the shortage in vaccine supply, intradermal immunization to save VLPs should be considered, so that a delay in vaccination in LMICs may be avoided. While switching to intradermal administration will take time and effort, it may be useful for other antigens at a later point Studies will have to be conducted to look at the effectiveness of the vaccination of SWs, both for SWs themselves (disease prevention) and for society, by reducing transmission from a potential reservoirFurther studies are needed to substantiate the evidence that vaccination after excision of pre-cancerous lesions helps to reduce the persistence and/or recurrence of the lesions.Many evidence gaps exist, making further studies necessary. The following studies were suggested:Based on the data presented and the discussion that took place, it can be concluded that it is premature to introduce routine vaccination of adults, as the information is incomplete and many further studies are needed (see above) to fill the knowledge gaps.Given the limited HPV vaccine supply in the short term, the vaccination of adults should not consume vaccine doses. Vaccination of younger age cohorts remains the priority, especially in LMICs, as these are the countries with the highest burden of HPV-associated cancers.


A fully government-funded human papillomavirus (HPV) vaccination program started in 2007 in Spain (only 11–14-year-old girls). The first of those vaccinated cohorts, with the quadrivalent vaccine (Gardasil), turned 25 years old in 2018, the age at which cervical cancer screening begins in Spain. The current study could provide the first evidence about the effectiveness of the quadrivalent vaccine against HPV in Spain and the influence of age of vaccination. The present ambispective cohort study, which was conducted on 790 women aged 25 and 26 years old, compares the rate of HPV prevalence and cytologic anomaly according to the vaccination status. The overall infection rate was 40.09% (vaccinated group) vs. 40.6% (non-vaccinated group). There was a significant reduction in the prevalence of HPV 6 (0% vs. 1.3%) and 16 (2.4% vs. 6.1%), and in the prevalence of cytological abnormalities linked to HPV16: Atypical Squamous Cells of Undetermined Significance (ASCUS) (2.04% vs. 14%), Low-grade Squamous Intraepithelial Lesions (LSIL) (2.94% vs. 18.7%) and High-grade Squamous Intraepithelial Lesion (HSIL) (0% vs. 40%), in the vaccinated group vs. the non-vaccinated group. Only one case of HPV11 and two cases of HPV18 were detected. The vaccine effectively reduces the prevalence of vaccine genotypes and cytological anomalies linked to these genotypes. The expected benefits of vaccination against human papillomavirus (HPV) infection are a reduction in the prevalence of infection, cytological abnormalities in the cervix and genital warts. The effectiveness of a population-based vaccination program with the quadrivalent HPV vaccine has been investigated previously ,3,4,5,6.®, covering HPV types 6-11-16-18) was established in 2007 for 11–14-year-old girls. Vaccine genotypes 16 and 18 cause preneoplastic lesions and cervical cancer, and vaccine genotypes 6 and 11 cause genital warts . Women vaccinated at 14 years old or younger had a prevalence of HR-HPV of 24.4% (81/332), while in women vaccinated at 15 years old or older the prevalence was 45.1% (37/82) [OR 0.39 (95%CI: 0.23–0.64) Regardless of the vaccination status, the five most prevalent HR-HPV types were 51 , 39 , 66 , 16  and 52 . Among the HPV positive population, HPV16 was 10.82% (33/314) and rose to 14.6% (33/231) among the HR-HPV population. The global prevalence of HPV-LR types 6, 11 and HR-HPV type 18 was 0.6 (5/790), 0.1 (1/790) and 0.3% (2/790), respectively. p = 0.009) was shown for HPV 16 between VG vs. NVG  (OR 2.63 (95%CI: 1.23–5.60)), which represents a reduction of 60%. Additionally, a significant reduction (p = 0.01) in the prevalence of HPV-LR 6 (1.3% vs. 0%) was observed, which represents a reduction of 100%, although the number of positives was very low. No significant differences were found for HPV 18, 31, 33 or 45. All results can be seen in When analyzing the genotypes targeted by the quadrivalent vaccine, a statistically significant reduction  of the total women studied had a normal cytological study, compared to 21% (165/782) with abnormalities: Atypical Squamous Cells of Undetermined Significance (ASCUS. 55.15% (91/165)); Low-Grade Squamous Intraepithelial Lesion (LSIL. 40% (66/165)) and High-Grade Squamous Intraepithelial Lesion (HSIL. 4.84% (8/165)). In VG, the rate of global cytological alterations was 21% (86/409), while in NVG it was 21.1% (79/373) OR: 1 (95%CI: 0.71–1.42). There were also no statistically significant differences when comparing the rates of ASCUS, LSIL and HSIL between the vaccinated and the non-vaccinated group .p = 0.0001) , compared to 12.4% (69/554) among HR-HPV-negative women OR: 5.11  .p = 0.001). For the remaining HR-HPV, there was no significant differences, except for genotype 56 for normal cytology, in which the frequency was significantly lower in the vaccinated group compared to the non-vaccinated (0.61% vs. 3.06%. p = 0.02)  and HPV 51 in VG (17.44%. 15/86). However, the presence of HPV 16 in abnormal cytology in VG was only 2.32% (2/86) ( = 0.02) . p = 0.13). The ≤14 years old vaccinated subgroup had a prevalence of abnormal cytology of 19.5% (64/328), while the ≥15 years old vaccinated subgroup was 27.2% (21/77). OR 1.54 , making it three times more likely to present an LSIL cytology if vaccination is performed after 15 years old.When we repeated the sub-analysis on vaccination age and rate of ASCUS and LSIL, we did not find significant differences for ASCUS, showing an OR 0.7 (95%CI: 0.30–1.62), but for LSIL, the prevalence is the highest in the group vaccinated late (16.8% vs. 6.4%) with an OR 2.96 , which means that the NVG is six times more likely to have an altered cytology related to HPV 16 than the group that was vaccinated. The OR of having an altered cytology related to HPV 16 according to the vaccination status is 6.22  (1/34 vs. 6/32) with p = 0.037. There was no HSIL in VG compared to two cases of HSIL in NVG (p = 0.206). In this study we show that vaccination against HPV at an early age (11–14 years old) in a cohort of Spanish girls is effective, diminishing the prevalence of HPV 6 and 16, as well as of cytological abnormalities.The overall prevalence of HPV infection in our study is 10% higher than that described in other reports previously published in Spain . In contAdditionally, in a similar report in the culturally close Italian population, Carozzi et al. (2016) found a HR-HPV infection prevalence 8% lower than we do for a comparable age group . In our study, NVG presents a lower use of condoms vs. VG (significant differences), which seems to indicate that women belonging to VG present greater awareness and take more protective measures against HPV. In both groups, a high number of sexual partners is observed, suggesting a change in sexual habits leading to greater promiscuity, which could explain the high global prevalence of HPV infection found. Although there is a tendency for vaccinated and unvaccinated women to have different habits, there are parameters of sexual habits that have not been collected in the study and therefore cannot be evaluated, constituting a limitation of the study.Although no statistically significant differences were found between the vaccinated and non-vaccinated population regarding the overall rate of HPV infection in our study, Steben’s review carried out in Canada showed an even higher prevalence of HPV infection in the unvaccinated population (47.2%), meanwhile the prevalence rate for the vaccinated individuals is similar to what we report (36.1%) .Our study reveals that there were differences in the detection rate of HR-HPV between the group of normal and altered cytology regardless of the vaccination status, which is similar to that described by Castellsagué  and the Critically, however, we show that HR genotype 16, which is highly prevalent in the unvaccinated population (6.1%) is found in just 2.4% of the vaccinated individuals, being displaced from the top five most prevalent genotypes found in this experimental group, undoubtedly due to the protective effect of the vaccine. Accordingly, Garland SM , this reOn the other hand, we found a prevalence decrease of nearly 100% for genotype HPV 6, which is even higher than that also reported by Tabrizi  (84%).Remarkably, we report no significant differences in the global HPV infection rate nor in global infection by high-risk HPV between the vaccinated and the non-vaccinated groups, coinciding with that reported by Carozzi et al. . This caA specific subanalysis focused on HPV-16 regarding the age at which the vaccine was received suggest that people vaccinated at age 15 or older could be more likely to be infected with HPV16 than those vaccinated at age 14 or younger. This could explain why 39.47% (33/76) of women who were vaccinated at 15 years of age or older had initiated sex prior to administration. These data, which suggest the importance of getting vaccinated at an early age, ideally before being exposed to HPV, are consistent with the report by Lei et al. ,20,21,22In our study, we found a global rate of cytological alterations higher than that reported by the College of American Pathologists (CAP)  , and by Importantly, when considering specifically HPV 16, we did find differences between the vaccinated and the non-vaccinated groups regarding the overall rate of cytological abnormalities present. Women vaccinated from 15 years of age are 1.5 times more likely to have an abnormal cytology with LSIL being almost three times more frequent. These findings are consistent with those reported by Castle et al. in 2019 , in whicThe presence of HPV 16, regardless of the vaccination status, is related to a greater risk of presenting an altered cytology compared to when HPV 16 is not detected. The presence of HPV 16 multiplies by 3.78 the probabilities of having an abnormal cytology when this group is compared to the rest of the studied population (including both negative HPV and other HPV genotypes), which stresses the importance of this genotype in the genesis of abnormal cytology.In the unvaccinated population, there are six cytological abnormalities linked to HPV16 for each abnormality found in the vaccinated group which reinforces the efficacy of the vaccine in preventing cervical lesions of cervical cancer.When we study the prevalence of ASCUS and LSIL related to HPV16, comparing the vaccinated and non-vaccinated groups, we found that both are significantly higher in the non-vaccinated. Differences in HSIL are also noted, but the low n of these cases means there is no statistical power to demonstrate differences. There was no HSIL in the vaccinated group versus two cases of HSIL in the non-vaccinated group. All of the above shows the clear effect of the protection developed by the vaccine. Not being vaccinated increases the probability of presenting an ASCUS or LSIL related to HPV 16 by five times. These data are consistent with what was reported by Ozawa .The differences found in the prevalence of HR-HPV and HPV16, in the incidence of cytological ASCUS and LSIL, are significant when comparing the group with early vaccination (14 or less) with late vaccination (15 or more), always with more unfavorable data. In this last group, which supports the importance of being vaccinated before the start of sexual activity, it is considered that these differences are due to this factor since 39% of the patients vaccinated subsequently (15 years or older) were already sexually active before being vaccinated, so they had been exposed to the infection before being immunized against only 5% of women who were sexually active before being vaccinated in the early vaccination group (14 years or younger).This study has some limitations related to a low value of n to evaluate some alterations (HSIL) that in themselves have a low prevalence. It would also have been necessary to expand this n to demonstrate differences with respect to less frequent vaccine genotypes (HPV 11 and 18). The non-differentiation in the vaccinated group of the age at which the vaccine was received may lead to a bias in the comparisons with the unvaccinated group given the lower effectiveness observed when the age of vaccination was 15 years or older.Finally, the five high-risk HPV types included in the nonavalent vaccine, compared to the quadrivalent vaccine  are present in 14.43% (114/790) of our study population. Assuming 100% preventive efficacy of the nonavalent vaccine against these five types, the use of the vaccine could lead to a reduction of 14.43% in their prevalence and a reduction of 6.58% (52/790) in the rate of cytological alterations produced by them. The vaccine effectiveness is demonstrated, showing a reduction in the prevalence of the HPV 6 and 16 vaccine genotypes in the group that was vaccinated as well as a reduction in cytological alterations related to HPV 16.


Human papillomavirus (HPV) vaccination disparities between urban and rural regions may moderate the vaccine’s impact on reducing cervical precancer (CIN2+) and cancer incidence. We assessed population-level trends in CIN2+ incidence (2008–2018) in urban and rural areas among Medicaid-enrolled women aged 18–39 years in Tennessee, United States. A sub-group analysis among women screened for cervical cancer was conducted to control for changing screening trends. CIN2+ incidence among young women aged 18–20 and 21–24 years, who most likely benefited from the HPV vaccine, declined similarly between urban and rural areas, although significant declines began earlier in urban versus rural areas. Our results suggest evidence of HPV vaccine impact regardless of urbanicity but demonstrate lagged impact in rural areas. These findings emphasize the importance of reducing barriers to HPV vaccination, particularly in rural areas, to improve the reduction of cervical precancer and cancer incidence, toward the World Health Organization’s goals of eliminating cervical cancer.Disparities in human papillomavirus (HPV) vaccination exist between urban ) and rural (non-MSAs) regions. To address whether the HPV vaccine’s impact differs by urbanicity, we examined trends in cervical intraepithelial neoplasia grades 2 or 3 and adenocarcinoma in situ  incidence in MSAs and non-MSAs among Tennessee Medicaid (TennCare)-enrolled women aged 18–39 years and among the subset screened for cervical cancer in Tennessee, United States. Using TennCare claims data, we identified annual age-group-specific  CIN2+ incidence (2008–2018). Joinpoint regression was used to identify trends over time. Age–period–cohort Poisson regression models were used to evaluate age, period, and cohort effects. All analyses were stratified by urbanicity (MSA versus non-MSA). From 2008–2018, 11,243 incident CIN2+ events  were identified among TennCare-enrolled women aged 18–39 years. CIN2+ incident trends (2008–2018) were similar between women in MSAs and non-MSAs, with largest declines among ages 18–20 : −30.4, 95% confidence interval (95%CI): −35.4, −25.0; non-MSA AAPC: −30.9, 95%CI: −36.8, −24.5) and 21–24 years . Significant declines for ages 18–20 years began in 2008 in MSAs compared to 2010 in non-MSAs. Trends were largely driven by age and cohort effects. These patterns were consistent among screened women. Despite evidence of HPV vaccine impact on reducing CIN2+ incidence regardless of urbanicity, significant declines in CIN2+ incidence were delayed in non-MSAs versus MSAs. The current nonavalent human papillomavirus (HPV) vaccine can prevent up to 90% of cervical cancer cases . DespiteIn the US, the HPV vaccine is covered for all children up to age 18 years under the federal Vaccines for Children program. While studies have documented overall declines in HPV-related adverse health outcomes among younger age groups who were most likely to have benefited from the introduction of the vaccine, disparities in HPV vaccination exist between urban and rural geographical regions ,5,6,7,8,Similar geographic disparities have also been demonstrated among adults, with 42% lower odds of HPV vaccine initiation for adults aged 18–26 years in rural areas compared to urban areas across eight US states . Given tLow- and middle-resource countries have added barriers to HPV vaccination, including lack of vaccine availability due to the high cost of the vaccine, difficulties with implementing routine adolescent immunization programs, and competing health priorities . Thus, eA few studies have examined trends in HPV-associated health outcomes by urbanicity ,13,14,15an HPV screening examination: International Classification of Diseases 9th revision (ICD-9) code V73.81 or International Classification of Diseases 10th revision (ICD-10) code Z11.51; ora Papanicolaou test: ICD-9 codes V72.31, V72.32, V76.2, V76.47, 795.06, 91.46, or ICD-10 codes Z01.411, Z01.419, Z01.42, Z12.4, Z12.72, R87.614, or Current Procedural Terminology (CPT) codes 88141-88145, 88147-88148, 88150-88158, 88164-88167, 88174-88175, or Healthcare Common Procedure Coding System codes P3000-P3001, G0101, G0123-G0124, G0141, G0143-G0145, G0147-G0148, Q0091; oran HPV deoxyribonucleic acid (DNA) test: ICD-9 codes 795.05, 795.09, or ICD-10 codes R87.10, R87.820, or CPT codes 87620-87622, 87623-87625.The Medicaid program is a federal public insurance program in the US that covers low-income individuals. In the state of Tennessee, the Medicaid program is called TennCare. We used TennCare billing claims data to identify women aged 18–39 years who were enrolled in TennCare from 2008 to 2018. For the subset of screened women, we identified TennCare-enrolled women who were screened for cervical cancer at least once during any given year using billing codes for:To examine CIN2+ trends by urbanicity, women with missing data on residence were excluded. Urbanicity was categorized by county of residence using the MSA definitions and boundaries set by the US Census Bureau . Urban arelevant diagnoses: CIN2+ tissue, non-specific CIN, high-grade squamous intraepithelial lesion cytology, CIN grade 1 tissue, low-grade squamous intraepithelial lesion cytology, and atypical squamous cells of undetermined significance; and/orcervical screening: HPV screening examination, Papanicolaou test, and HPV DNA test; and/orrelevant procedures: cervical treatment procedures and cervical or vaginal biopsies.Incident CIN2+ events, including cervical intraepithelial lesions grades 2 and 3, and adenocarcinoma in situ, were identified by a validated claims-based model using billing codes among women with cervical diagnostic procedures who were consecutively enrolled in TennCare for at least one year from their diagnostic procedure date, as previously described in detail . BrieflyAll corresponding billing codes have been provided previously . For theAnnual person-years for each age group  were estimated by counting the total number of women who were enrolled in TennCare on July 1 of each year with at least one year of consecutive enrollment. For example, total person-years for 2008 comprised TennCare-enrolled women who were continuously enrolled between 1 July 2007, and 1 July 2008. Screened person-years included the subset of total women who had a least one cervical cancer screening code during the year prior to July 1 of each year. Only women residing in an MSA or non-MSA county on July 1 of each year were counted toward the person-time estimation for MSA and non-MSA populations, respectively. Annual CIN2+ incidence rates per 100,000 person-years were calculated by dividing the total number of women meeting the incident CIN2+ event definition by the estimated person-time for each year and age group among all women and those residing in MSA and non-MSA counties and then multiplying by 100,000.We identified CIN2+ incident trends and significant changes in CIN2+ trends  over time using the Joinpoint Desktop Software version 4.5.01 , which calculated average percent changes  and average annual percent changes  from 2008 to 2018, by urbanicity [Age, period, and birth cohort effects were evaluated using the Clayton and Schiffler modeling approach for age–period–cohort analyses . Age efff, g, and h, represent the functions for each effect [The Clayton and Schiffler model building process begins with an age model, then adds a “drift” parameter  . Derivath effect . SynthetBecause of the linear dependency between age, period, and cohort effects (C=P-A), the simultaneous linear effects of all three effects cannot be estimated; therefore, any parameterization of the age–period–cohort model included two fixed levels and one slope among the three functions . We parap-values <0.05 were considered statistically significant.Model goodness-of-fit was examined using residual deviance statistics. Using the Clayton and Schiffler approach , model fBetween 2008 and 2018, we identified 7956 incident CIN2+ events in MSA counties, compared to 3287 incident CIN2+ events in non-MSA counties  .Of the total number of events, 10,540 (94%) women  had a cervical screening code identified in the year prior to their incident event. Among women residing in MSAs, CIN2+ incidence significantly declined from 2008 to 2018 for those aged 18–20 years , 21–24 years , 25-29 years , and 35–39 years  .However, after restricting to screened women, declines in CIN2+ were only observed for the youngest three age groups. Among women residing in non-MSAs, CIN2+ incidence significantly declined for those aged 18–20 years , 21–24 years , 25–29 years , and 30–34 years . Again, after restricting to women who were screened for cervical cancer, significant declines were only observed for the three youngest age groups.Several Joinpoint-detected inflections  were identified . Among wWomen residing in MSAs showed similarities in CIN2+ incidence rates by period and birth cohort compared to women residing in non-MSAs . Patternp < 0.001). The best-fitting model included all three effects (age–period–cohort), indicated by the lowest residual deviance, for women residing in MSAs  and non-MSAs . Model comparisons demonstrated notably larger cohort than period effects .Age–period–cohort Poisson regression models indicated decreasing CIN2+ incidence from 2008 to 2018 for both MSAs (EAPC: 0.90%/year) and non-MSAs (EAPC: 0.89%/year) . SignifiAmong screened women, age–cohort and age–period–cohort models had similar goodness-of-fit, with slightly better fit for age–period–cohort models , 301.1 versus 296.9 (non-MSA)) .p > 0.05); however, the drift, nonlinear cohort effects, and cohort effects adjusted for period effects were significant (p < 0.001).Among screened women residing in MSAs, cohort effects were larger than period effects (change in deviance for nonlinear cohort effects versus nonlinear period effects: 266.3 versus 15.6). Among screened women residing in non-MSAs, nonlinear period effects and period effects adjusted for cohort effects were not significant  and age effects , even after adjusting for period effects. Specifically, young women in more recent generations had lower rates of CIN2+ compared to young women born earlier. Cohort effects were likely due to generational differences in vaccine eligibility, vaccination behaviors, and screening recommendations in the US. When the Food and Drug Administration approved the first quadrivalent HPV vaccine in 2006 for females aged 9–26 years , older wOur finding of significant age effects may be explained by age-associated social and biological factors regarding the HPV vaccine. Among age-eligible adults aged 18–26 years, HPV vaccination coverage in the US has been historically low, ranging from 22.1% to 39.9% for initiation and 13.8% to 21.5% for completion from 2013–2018 . AdditioFor urbanicity-stratified CIN2+ incidence by age group over time, we found similar patterns and evidence of HPV vaccine impact on reducing CIN2+ incidence in both MSAs and non-MSAs, despite varying HPV vaccination coverage by urbanicity. In Tennessee from 2016 to 2019, HPV vaccination in MSAs ranged from 66% to 69% for initiation and 46% to 47% for completion, compared to 46% to 53% for initiation and 25% to 34% for completion in non-MSAs . While HAmong women who were screened for cervical cancer, HPV vaccine impact was still evident in MSAs and non-MSAs, with similar declining CIN2+ incidence in young, screened women (aged 18–20 and 21–24 years) residing in MSAs and non-MSAs. However, in MSAs, significant declines were observed in screened women aged 25–29 years, while declines in non-MSAs for this age group were not significant. This may be due to improved accessibility of HPV vaccination in urban centers upon first release. Delays in HPV vaccination access and distribution within non-MSAs due to lack of healthcare sites, limited transportation, or other barriers may have contributed to a smaller initial impact of the HPV vaccine. However, similar declines in CIN2+ incidence in both MSAs and non-MSAs for younger cohorts indicate that non-MSAs were able to overcome initial barriers to HPV vaccination to have a comparable vaccine impact to MSAs. Further, age, period, and cohort effects were all significant among screened women residing in MSAs, while only age and cohort effects were significant for those residing in non-MSAs. However, because our sample size for women residing in MSAs was roughly double that of non-MSAs, we cannot rule out the possibility that differences between MSAs and non-MSAs were also due to differences in power and sample size.Our study has limitations. The study represents a unique population of Tennessee Medicaid women; thus, results may not be generalizable to other geographical regions or to populations of higher socioeconomic status. For instance, Medicaid populations have very low cervical cancer screening rates compared to the general US population . AdditioOur study has notable strengths. This is the first study to describe CIN2+ incident trends by urbanicity using a validated claims-based model, demonstrating the applicability of utilizing claims data for CIN2+ surveillance research. Examining population-based CIN2+ trends in the US is costly and limited to populations with adequate surveillance of cervical biopsies through the New Mexico HPV Pap Registry  and the In summary, we demonstrated significant declines in CIN2+ incidence in both MSAs and non-MSAs among TennCare-enrolled women, particularly in younger women who likely benefited from the HPV vaccine. CIN2+ trends were mostly driven by age and cohort effects, but effects in non-MSAs were delayed compared to MSAs, suggesting an impact of lower vaccination rates and delayed increases in vaccination in non-MSAs. These results emphasize the importance of reducing barriers to HPV vaccination in lower resource settings, such as rural regions, to promote cervical cancer elimination.


This systematic review provided synthesized evidence regarding the effectiveness of the interventions promoting the human papillomavirus (HPV) vaccination in college-aged population. The HPV infection is the most prevailing sexually transmitted disease. Despite the availability and effectiveness of the 9-Valent HPV vaccine, the vaccine coverage among young adults remained low. In witness to the increasing burden of HPV-related infections and cancers, research focused on the vaccination interventions should be conducted to determine the effectiveness of the vaccination strategy and address the gap. The search was conducted through PubMed, Cochrane, and CINAL. Studies were included if they (1) included vaccination programs, (2) target population was young adults aged 17–26, (3) examined factors associated with the intervention effectiveness, (4) were published in English, and (5) were published between February 2010 and February 2020. HPV-related knowledge and intentions toward HPV vaccination were all reported increased after the intervention. Increased HPV vaccination intentions were found associated with the increased vaccine initiation and completion. Among bisexual or homosexual individuals, females were found more likely to complete the HPV dose 2 and 3. The review findings suggested using vaccination interventions incorporated with educational components to promote vaccine uptake among young adults. Supportive interventions tailored to different populations and settings are crucial to address the suboptimal HPV-related knowledge and vaccination status among the young beneficiaries. Human papillomavirus (HPV) infection has been found as the most common sexually transmitted disease and greatly linked with genital infections such as genital warts. Specific types of HPV virus are also found responsible for cervical cancers, oropharyngeal cancers, and cancers of the penis, vagina, or anus . Among wApproximately over 70 million people in the USA were found infected with HPV sometime during the late adolescence and young adulthood, and fourteen million people are newly diagnosed with the infection each year . RegardiThe available 9-valent HPV vaccine is found effective in prevention of more than 90% HPV-related cancers . The safDespite that the distribution of the 9-valent HPV vaccine started at the end of 2016, the vaccine uptake rates in the USA remained unsatisfactory and failed to meet the objectives of the Healthy People 2020 targeting for eliminating health disparities nationwide . As per In review of the previous research, systematic reviews of HPV were primarily related to the prevalence and disparities in HPV infections, the efficacy and safety of the HPV vaccines, the measurement used in vaccine acceptability, the predictors or factors regarding HPV vaccine acceptability, and the role of health care providers in improving the vaccination initiation. The evidence they had compiled provided some insights into vaccination interventions aiming at improving the vaccination coverage, but the comprehensive review combining the factors which contribute to HPV vaccination, with vaccination intervention development and vaccine uptake evaluations, is scarce , 17, 18.The aims of this study are to investigate the effectiveness of HPV vaccination interventions in college aged adults, critically evaluate and synthesize the intervention approach to improve vaccine coverage, also add insights into the feasibility and acceptability of the intervention, and further inform the practice and policy of the HPV vaccination among young adults. This present review embodies new emerging evidence and incorporates possible prerequisites for making informed decisions regarding HPV vaccination interventions at both the individual and community level. Countries out of the USA which achieved promising results of HPV vaccination campaigns were also included in the review to provide more insights across nations.This author searched the PubMed, Cochrane, and online version of Cumulative Index to Nursing & Allied Health Literature (CINAL) independently to identify peer-reviewed studies published between February 2010 and February 2020. The search was limited to English language and with keywords and relevant Medical Subject Headings (MeSH) subject terms, including HPV, human papillomavirus, vaccine or vaccination, immunization, uptake, intervention, and students. Finally, references from systematic reviews and references from the studies identified were also assessed for inclusion in the review process.Studies were eligible for inclusion if the following criteria were fulfilled: interventions were developed to increase HPV-related knowledge and vaccination rate and provided quantitative data for HPV vaccination coverage specifically. Interventional, observational, and systematic studies were all eligible. Studies that only provided qualitative results, only published as abstracts and protocols, or only assessed HPV knowledge, awareness, attitudes, intentions, and barriers to vaccination were excluded. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed during the search, both article titles and abstracts were scrutinized first, and then relevant full-text articles were obtained and reviewed by this author to further confirm that verification criteria were met.This author extracted information about intervention and assessed risk of bias. The risk of bias and the certainty in evidence were evaluated for each study by using the Cochrane Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. This approach results in three level of risk of bias and four levels of quality of evidence. Critical factors for determining the grade for each study are listed in detail for the approach, including the risk of bias, evidence quality rating scale, and descriptions of the ratings.Seventy-eight references had been screened, and a total of 10 relevant articles met the selection criteria for this review. One (10.0%) of the studies was a cross-sectional analysis . Three (n = 9) focused on college students, and one study included both employed women and undergraduate students for comparison. Three studies were conducted outside of the USA, including one in China and two in Canada. Sample size of participants in the studies ranged from 200 to 1703. Four studies recruited both male and female participants, with six studies focused on females only (see Table The study participants’ ages ranged from 18 to 38 years old. The majority of the studies (All the interventions targeted for boosting the human papillomavirus (HPV) vaccine acceptability and coverage among young adults. Among the ten interventions reviewed, five studies described the use of theory-based interventions, and key factors of the Health Belief Model (HBM), the Transtheoretical Model (TTM), and the Information, Motivation, Behavioral skills model (IMB) were reported to be applied to improve design of the interventions , 20, 23.α = .75~.95) [A range of pre- to post-intervention survey questionnaires and human papillomavirus (HPV) vaccine initiation and completion rates were used to evaluate the effectiveness of the interventions. Reasons stated for being unvaccinated were explored as well. The follow-up evaluations were conducted 3 months up to 1 year to measure the HPV vaccine dose initiation and completion. Instruments used in the studies examined the topics covering HPV-related and HPV vaccine knowledge and awareness, HPV and HPV vaccine beliefs and decision-making factors, self-efficacy, and vaccine uptake. Most of the studies used self-reported measurements, and two studies 20%) reviewed medical records for vaccine uptake assessment % reviewe. One stu.75~.95) , 19, 21..75~.95) .n = 7) did not address adequately follow-up, and nine studies had flawed measurement of outcomes due to the limited evidence of the instrument validity. Two studies were found to be of low risk of bias, four of medium risk, and four of high risk. Seven of the ten studies included in the review were graded as moderate level of quality of evidence, as a result of the majority of randomized controlled studies(n = 4) not specifying allocation concealment and blinding procedures, one study being observational and flawed design and measurements as potential threats to construct, internal, and external validity. Two randomized controlled studies discussed randomization procedures, one described the use of allocation concealment mechanism with sequentially numbered, opaque sealed envelopes, and another described that the investigators and research nurses in the field were blinded to the allocation sequence [All the studies lacked in-depth description of participant attritions, most of the studies -related infections, HPV vaccination intentions, and the vaccine uptake rates among college students aged 17–26. Constructs of the interventions and evaluations of the outcomes were also identified.In the review, all studies included vaccination interventions or programs that promoted the vaccination intentions and behaviors among college-aged students. Most of the studies assessed HPV-related knowledge, including the knowledge of cervical cancer, individuals’ perception of the risk of the disease, attitudes or intentions toward vaccination, and perceived barriers to the vaccination. The study participants’ intentions of receipt of the vaccine were found positively linked with improved awareness and knowledge of HPV-associated infections. These results imply that emphasizing the educational components in the development of vaccination intervention would improve the effectiveness of the intervention.A significant increase in the HPV-related knowledge, attitudes, and acceptability of the HPV vaccine were found in the study participants upon completion of the interventions , 19–22. Additionally, perceived severity of HPV infection, susceptibility to the HPV infection, and benefits of the vaccine were identified among the factors that positively affected the participants’ intentions to get vaccinated , 16. AddTwo major types of interventions emerged in the review, those with the theory-based approaches and those without. Promising health care outcomes were identified in both types in terms of the increased level of knowledge about the HPV infections and HPV vaccine. Increase in the HPV knowledge was found in the immediate post-intervention surveys while with one exceptional study identified significant improvement in HPV knowledge 3 months following the intervention –23. The The vaccination interventions identified in the review were also varied in settings and modalities to deliver. Most of the interventions had been completed in a one-time-only session, and reinforcement afterwards was provided in the form of reminding messages for the vaccine appointment or providing additional educational information –22. The This review only included peer-reviewed articles to facilitate the inclusion of relatively good quality work. During the review, a systematic approach was followed based on PRISMA checklist, and critical appraisal of each article was conducted following the guidance of the GRADE approach. The overall quality of the included studies was moderate, and campus-based convenience sampling, insufficient description of participant attritions and allocation concealment and blinding procedures in trial studies, self-reporting measures, and limited evidence of the instrument reliability and validity were found as the major factors that could possibly increase the risk of bias in the studies and jeopardize the transferability and generalizability of the study results. Several areas were prompted for future studies, which primarily centered on long-term assessments of the intervention effectiveness; development and evaluations of tailored vaccination interventions to manage the gender disparity, socioeconomic disparity, diversity in sexual orientation, and different ethnic groups; the difference in parental, peer, and interprofessional roles; and impact in health prevention regarding HPV-related infections and cancers. Moreover, in the light of generally low level of knowledge of HPV prevention and better immune response with the younger population, effective strategies addressing comprehensive and quality sexual health education at younger ages should be examined.On the whole, this review indicated the complex of contributing factors to a successful HPV vaccination intervention. The approaches adopted in the studies achieved higher level of HPV-related knowledge, vaccination intentions, and higher vaccination rates in comparison of the pre-intervention status. Insights and gaps identified in the review could possibly be applied to guide sexual health education and inform the policy of the HPV vaccination and other vaccine preventable diseases, especially for the vaccinations that are not included in the national program. More robust study designs for studying the associations between HPV vaccination interventions and vaccine uptake rates across different settings and populations are also underlined in the findings of the review.


The WHO recommends human papillomavirus (HPV) cervical self-sampling as an additional screening method and HPV DNA testing as an effective approach for the early detection of cervical cancer for women aged ≥30 years. This systematic review assesses end user’s values and preferences related to HPV self-sampling.We searched four electronic databases  using search terms for HPV and self-sampling to identify articles meeting inclusion criteria. A standardised data extraction form was used to capture study setting, population, sample size and results related to values and preferences.Of 1858 records retrieved, 72 studies among 52 114 participants published between 2002 and 2018 were included in this review. Almost all studies were cross-sectional surveys. Study populations included end users who were mainly adolescent girls and adult women. Ages ranged from 14 to 80 years. Most studies (57%) were conducted in high-income countries. Women generally found HPV self-sampling highly acceptable regardless of age, income or country of residence. Lack of self-confidence with collecting a reliable sample was the most commonly cited reason for preferring clinician-collected samples. Most women preferred home-based self-sampling to self-sampling at a clinic. The cervical swab was the most common and most accepted HPV DNA sampling device.HPV self-sampling is generally a highly accepted method of cervical cancer screening for end users globally. End user preferences for self-sampling device, method and setting can inform the development of new and expanded interventions to increase HPV screening. Self-sampling for human papillomavirus (HPV) DNA is effective at detecting cervical cancer and generally a highly acceptable form of cervical cancer screening to end users.Self-sampled specimens are seen as acceptable in terms of ease of use, convenience, privacy, and physical and emotional comfort .Preferences related to self-sampling including sampling device , method , setting  varied by region, subpopulation and age, though most end users found the process of self-sampling acceptable overall.End user preferences for self-sampling method, device and setting can inform the development of new and expanded interventions to increase HPV screening.Understanding end users’ preferences for self-sampling is critical for reaching the WHO global target of 70% HPV screening coverage by 2030.Cervical cancer is the fourth most common cancer among women globally, with the estimated 570 000 new cases yearly mostly affecting women between the ages of 30 and 49 years.5 6HPV DNA testing is recommended by WHO, the US Preventive Services Task Force and Australian, US and European national screening programme guidelines as an effective approach for the early detection of cervical cancer for women ≥30 years.14et al as the ‘collection of goals, expectations, predispositions, and beliefs that individuals have for certain decisions and their potential outcomes’.20Although previous reviews have found generally high acceptability of HPV DNA self-sampling, end users’ values and preferences regarding self-sampling method, device and setting have not been explored.We conducted this systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.21We defined HPV self-sampling as a process where a client who wants to know whether they have an HPV infection uses a kit to collect a cervicovaginal or urine sample, which is then sent for analysis by a laboratory. While self-sampled anal specimens can be collected for the detection of HPV DNA, these samples are likely to be indicative of risk for anal cancer rather than cervical cancer. Therefore, we only included articles that focused on cervicovaginal and urine samples given our interest in cervical cancer. Collection devices include lavage, brush, swab, tampon or labial padette and may occur in any setting . We defined HPV clinician sampling as any sampling method where a clinician or other healthcare provider obtains the cervicovaginal HPV DNA sample. HPV DNA testing does not provide a positive diagnosis for cervical cancer but rather identifies those end users at risk for developing cervical cancer in the future.Studies were eligible for inclusion if they met the following criteria: (1) included participants who performed cervicovaginal or urine self-sampling for HPV DNA; (2) measured general acceptability or characteristics of acceptability regarding cervicovaginal or urine self-sampling for cervical cancer or preference for setting for sampling ; and (3) published in a peer-reviewed journal prior to the search date. Both qualitative and quantitative studies were included.We searched four electronic databases  through 19 October 2018 using search terms for HPV and self-sampling. The full search strategy is described in a complementary review of the effectiveness of HPV self-sampling compared with clinician samplingArticles were screened based on relevance to each topic. Ongoing randomised controlled trials (RCTs) were hand-searched for through ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the Pan African Clinical Trials Registry and the Australian New Zealand Clinical Trials Registry. We conducted secondary searching of included articles and relevant reviews for additional studies that met the inclusion criteria. After initial title–abstract screening, full-text articles were obtained of all potential studies. Two reviewers independently assessed all full-text articles for study inclusion eligibility and resolved differences through consensus.Two reviewers independently used a standardised data abstraction form to capture information on location of study, study population, sample size and results related to values and preferences from each study. Differences in data abstraction were resolved through consensus, with a third reviewer as needed.For studies that presented quantitative data related to values and preferences, two reviewers extracted measures of acceptability and satisfaction and their ratings from the results related to values and preferences.For qualitative studies, we used an iterative approach to identify salient themes related to end users’ values and preferences. Codes were created based on recurring themes and applied to each article. One member of the study team read through each article and extracted themes inductively related to values and preferences for self-sampling. The study team met throughout the analysis process to discuss themes.We also stratified findings by end users’ age, location of study, self-sampling device, setting and subpopulation  to examine differences in values and preferences by these characteristics.A coding matrix was modified from the Evidence Project risk of bias toolMembers of the WHO patient safety working group provided feedback on the review during conceptualisation and protocol development. Patients were involved in a global survey of values and preferences conducted to inform the WHO guideline on self-care interventions; they thus play a significant role in the overall recommendation informed by this review.We retrieved 1847 records via electronic databases, with 11 additional citations reviewed from references listed in prior reviews, included studies, and hand-searches. After removing duplicate references and screening citations, we identified 72 unique studies presenting values and preferences data on HPV self-sampling .31–40Study populations typically included adult end users. Participants ranged in age from 14 to 80 years. Fourteen studies specifically targeted women who were under/never screened for cervical cancer.29Nine studies employed a qualitative design, specifically in-depth interviews and focus group discussions, to explore women’s preferences related to HPV self-sampling.Common issues with study quality were sampling/selection bias, lack of validation of survey measures and lack of transferability of values and preferences results. Twenty-seven articles reported sampling or selection bias as a limitation of the study.End users generally found HPV self-sampling acceptable and/or expressed willingness to undergo future HPV testing using self-sampling.Across most of the studies asking end users’ preference regarding self-sampling versus clinician sampling for HPV DNA, most end users chose self-sampling.27 28 31 33 35 37 39 40 46 52 59 65 69 70 72 73 77–80 89–91 94 95In nine studies, end users preferred clinician sampling over self-sampling.In 21 studies, end users self-sampled from their homes.70Other studies suggested strategies to increase end user’s confidence in performing self-sampling correctly.62 68 79 81Studies examined different HPV self-sampling devices. The cervical swab was by far the most common and well accepted. Other devices tested included the lavage,29Several studies assessed women’s preferences for different self-sampling devices and acceptability was generally high for all devices.51Two studies examined acceptability of an alternative method for cervicovaginal HPV DNA self-sampling, urine self-sampling.Three studies focused solely on the values and preferences of AGYW.63Twenty-five studies compared differences in sampling preferences by age group.24Only one study compared end users’ preferences across different regions and countries.Three studies examined HPV sampling preferences among end users living with HIV.Two studies conducted in the USA examined preferences among sexual and gender minorities. As mentioned previously, more than half of lesbian and bisexual AGYW surveyed reported willingness to self-sample at home.62et al, which reported a pooled estimate prevalence of women preferring self-sampling of 59% (95% CI 48% to 69%).et al.In this systematic review, we found general consensus that self-sampling is a highly acceptable method for HPV testing, regardless of study location and sampling method, device, setting or participant demographics. Our findings align with previous reviews, such as one by Nelson A number of studies examined acceptability of self-sampling in different settings, such as the clinic, home or community. More than half of home-based self-sampling studies took place in high-income countries, since a quick and reliable postal system was necessary for mailing the samples for processing. In some low-income and middle-income countries, community health workers collected specimens self-sampled by participants for processing during home-visits. Across studies, the home was regarded as a highly acceptable and convenient setting for self-sampling. However, women expressed that they would prefer clinic-based sampling if home-based sampling meant they would not have access to a healthcare provider. Ensuring that women have access to a healthcare provider to answer questions about screening or a potential positive result is an important consideration for the expansion of home-based testing programmes.The most common device for self-sampling was the cervical swab. Among studies comparing acceptability of different self-sampling devices, end users preferred the cervical swab over other devices such as the lavage or cervical brush, but this preference could be due to greater familiarity with cervical swab. Studies examining less commonly used devices  and methods  generally found high acceptability; however, only 15 studies examined these alternative self-sampling devices and methods. Therefore, preference for self-sampling device and method is an important area for further study.This review identifies a need for further research examining women’s preferences in low-income countries, which bear a disproportionate burden of new cervical cancer cases. Only 3 of the 72 studies included in this review were conducted in low-income countries, leaving a critical gap in understanding of end users’ preferences in these settings. HPV DNA self-sampling is a promising screening method that, when offered to women in low-resource settings, can address barriers that create inequalities in access to cervical cancer screening.97This is one of the first studies to systematically review both qualitative and quantitative literature on values and preferences for HPV self-sampling for cervical cancer screening. We synthesised end users’ values and preferences related to the setting of sample collection and the device used to collect the sample. We also examined values and preferences for HPV self-sampling among vulnerable populations.Findings from this review should be viewed in light of its limitations. We did not include conference abstracts or grey literature in this review, so our findings may not fully represent of the full body of literature on values and preferences for HPV self-sampling. Given the diversity of measures used to assess values and preferences, it is difficult to make comparisons across studies and therefore difficult to determine the specific aspects of self-sampling that clients find acceptable and whether these hold true for clients in different age groups, geographic regions and socioeconomic status.WHO strongly supports inclusion of self-sampling for HPV testing as an additional approach to sampling in cervical cancer screening programmes where HPV tests are used. HPV self-sampling is generally a highly accepted method of cervical cancer screening for women across the world. This systematic review of values and preferences builds on previous reviews on self-sampling acceptability. Understanding women’s preferences for HPV self-sampling is a critical factor for expanding choice, coverage and uptake of cervical cancer screening. This will be critical to reach WHO’s target of 70% cervical cancer screening coverage by 2030.98