HPV vaccine is a prophylactic vaccine to prevent HPV infections. Recommended by the World Health Organization, this vaccine is clinically proven to be one of the most effective preventive measures against the prevalence of cervical cancer and other HPV-associated cancers and chronic genital conditions. However, its uptake rate among women in Hong Kong is insignificant—only approximately 2.9% adolescent girls and 9.7% female university students received HPV vaccination in 2014. With the notion of Critical Medical Anthropology, we aimed to identify if different influential factors, ranging from individual, societal, and cultural, are involved in the decision-making process of whether to receive HPV vaccination.We adopted a qualitative approach and conducted in-depth individual semistructured interviews with 40 women in Hong Kong between May and August 2017.We noted that the following factors intertwined to influence the decision-making process: perceptions of HPV and HPV vaccine; perceived worthiness of HPV vaccines, which was in turn influenced by vaccine cost, marriage plans, and experiences of sexual activities; history of experiencing gynecological conditions, stigma associated with HPV vaccination, acquisition of information on HPV vaccines, distrust on HPV vaccines, and absence of preventive care in the healthcare practice.HPV vaccination is promoted in a manner that is “feminized” and “moralized” under the patriarchal value system, further imposing the burden of disease on women, and leading to health inequality of women in pursuing the vaccination as a preventive health behaviour as a result. We believe that this ultimately results in an incomplete understanding of HPV, consequently influencing the decision-making process. The “mixed-economy” medical system adopting capitalist logic also molds a weak doctor–patient relationship, leading to distrust in private practice medical system, which affects the accessibility of information regarding HPV vaccination for participants to make the decision. HPV vaccine is a prophylactic vaccine to prevent HPV infections. Recommended by the World Health Organization (WHO) , it is eSince licensure in 2006, HPV vaccines have been introduced for women in many countries and included in the immunization program of these places in order to prevent cervical cancer . AustralHowever, the situation in the Asian Pacific region is different from the general trend. Except for Australia, HPV vaccination coverage in this region is relatively low. In more affluent countries, such as Japan and Korea, or less affluent ones, such as Thailand and Cambodia, the HPV vaccination coverage has been approximately 10% in the current decade . Hong KoThe acceptability of vaccines by women is apparently influenced by various factors, such as information pertaining to , 29, 32 It is not always straightforward for people to accept the idea of vaccination, and vaccine hesitancy , 45, whiPeretti-Watel et al.  suggesteBased on these theoretical viewpoints, vaccine hesitancy should not be interpreted as merely a behavioural outcome; it is more appropriate to consider it as a decision-making process , 48, sinThe Strategic Advisory Group of Experts , part ofThe formulation of vaccine hesitancy suggested by SAGE offers a tripartite model  to understand core determinants affecting the decision-making process regarding HPV vaccination. Although the “three Cs model” suggests that vaccination hesitancy should be interpreted as a decision-making process, it is a summary model without delineating the interaction of different individual, social, and cultural factors. This paves the gap of the vaccination studies in current literature. Health Belief Model and Theory of Planned Behavior are the most popular behavioral health theories that have been used in the vaccination studies , 17. HowThe HPV vaccination rate has been low among women in Hong Kong , and durWe adopted a qualitative approach to conduct an in-depth investigation of elements that influence the decision-making process of women regarding HPV (non) vaccination in Hong Kong. Individual semistructured interviews were conducted to gain an in-depth understanding of the complex social and cultural processes that govern this decision.Forty female participants were interviewed between May and August 2017. Purposive sampling was employed for participant recruitment, with the following sampling criteria: (1) women aged 18–59 years at the time of the study, (2) lived and received education in Hong Kong since birth, and (3) Hong Kong Chinese in ethnicity. HPV vaccination is suggested for women aged ≥9 years in Hong Kong ; howeverThe participant recruitment process was conducted in two stages. First, posters were put up in public facilities in a university campus in April 2017, which resulted in the successful recruitment of 10 participants. The majority of them were < 30 years of age and had received HPV vaccination at the time of the study. Second, to ensure a wider sociodemographic mix of participants, the next round of recruitment was conducted in the community, resulting in the recruitment of 30 women. Posters were put up in a primary care clinic at a residential new town—Tseung Kwan O—from May to June 2017, targeting women who were aged ≥30 years. Among all the residential new towns in Hong Kong, Tseung Kwan O had the third highest population, with the third highest percentage of population having attained postsecondary education, and with the second highest labor force participation rate and median monthly income  saw an advertisement about the cervical cancer vaccine. It is said that if we want to protect ourselves from cervical cancer, then we should get the jabs. The advertisement just mentions cervical cancer … It is an advertisement for cervical cancer. I don’t know if the vaccine can prevent other diseases. [Participant 18]Only a few participants knew that HPV can lead to genital warts; however, they rarely knew that HPV vaccination can also help prevent genital warts:HPV mainly results in cervical cancer? And other diseases such as … hmm … I am not sure … but maybe something related to the sexual organ, like [genital] warts. I have heard about HPV vaccination; it is for the prevention of cervical cancer. [Participant 6]The most prominent understanding among participants was that HPV vaccination can prevent cervical cancer; most were unaware of the other uses of HPV vaccine, although they knew that the vaccine has other preventive uses:I know that the vaccine can prevent cervical cancer and hmm … some kinds of viruses … I remember that I once got a leaflet stating that the vaccine can prevent some diseases … and cervical cancer. Sorry, I can recall cervical cancer only. [Participant 1]In most cases, participants called HPV vaccine “cervical cancer vaccine.” This “nickname” made them believe that the vaccine is exclusively for women and only for the prevention of cervical cancer:When I saw the information about the vaccine, I thought that it is great to have a new way to protect women. I think the vaccine is for women only, because the vaccine is a cervical cancer vaccine, so it prevents cervical cancer. Only women will suffer from it. Men will never have this disease. [Participant 37]The Chinese naming of HPV vaccine thus led participants to focus on its efficacy against cervical cancer only and overlook its other preventive uses. In addition, female celebrities involved in promoting the vaccine via advertisements, which most participants found impressive, further presented the vaccine as being exclusively for women:There are two brands of HPV vaccines. One has Ah Sa [a female Hong Kong singer] as the spokesperson, and the other has GEM [a female Hong Kong singer] as the spokesperson. We [my friends and I] call those vaccines as “Ah-Sa-vaccine” and “Ah-GEM-vaccine”. I think this vaccine is clearly for women only, because Ah Sa and GEM are women. [Participant 4]Besides the relationship between HPV and cervical cancer being the most prominent understanding among participants, the relationship between HPV and AIDS was also a prominent stereotype. HIV is literally similar to HPV, which seemed to confuse some participants as they misinterpreted HPV as HIV:HPV? Is it the cause of AIDS? I remember that AIDS is caused by a virus that has these 3 alphabets. [Participant 35]The participants’ perceptions on HPV and HPV vaccine could influence their health behaviour and their decision-making process. All participants had some understanding about the relationship between HPV and cervical cancer and about HPV vaccination being a preventive measure for cervical cancer. Most participants believed that HPV vaccination could only confer protection against cervical cancer:Although all participants had good knowledge about the preventive use of HPV vaccine against cervical cancer, not many non-vaccinated participants were motivated to get vaccinated. One of the barriers was the cost of the vaccine, in particular the high cost of the vaccine failed to make the vaccine to become prioritized in participants’ thoughts:I could get a discount [for the HPV vaccine] when I was studying at university. However, I didn’t have a stable income at that time, so I did not get vaccinated. It doesn’t mean that I didn’t want to get the vaccine, but just that I didn’t want to spend such a large amount of money on the vaccine at that time. It was more sensible to spend those thousands on other more important things at that time. Getting vaccinated was not a priority for me at that time. [Participant 7]It appeared that if the vaccine was offered at a discounted cost, participants had a higher incentive to get vaccinated and were thus more motivated:I took the jabs when I was a final year [undergraduate] student. There was a promotion booth [of HPV vaccine] in the campus … It was pretty expensive, but the cost had already been discounted. It would be even more expensive if I took the jabs outside the campus after I had graduated. [Participant 4]On the other hand, price of the HPV vaccine can be varied in different private practice healthcare providers, and some participants were suspicious about the varied costs of the vaccines, making them hesitant to get vaccinated:I wanted to get the vaccine before, so I asked [the clinic] about the cost [of the HPV vaccine]. I was told that there was a vaccine which could prevent 9 types of (HPV) viruses, costing around 2,000 dollars. I thought the cost was okay. But later when I asked [about the vaccine] again, the clinic told me that there was a new [HPV] vaccine which could provide more protection but would cost around 4,000 dollars. It was really expensive … I wondered whether launching a new vaccine is a way for pharmaceutical companies to make profit. Finally, I did not take the vaccine. [Participant 35]Although HPV vaccines are available on a self-pay basis to most middle- and high-income female population in Hong Kong, the cost alone cannot completely explain the decision-making process—to participants, the cost did not just imply how much would they have to spend, but it also referred to whether the vaccine was worth getting at all. Such an assessment of worthiness was in fact a complex process: it involved the perceived efficacy of the vaccine by participants in relation to their risk perception of developing cervical cancer and/or other HPV-associated conditions (if the participant could recognize those possible conditions). The perceived worthiness of the vaccine was correlated with marriage plans:I read the advertisement of HPV vaccination... I know that the vaccine can prevent cervical cancer. However, I don’t think I have an urgent need to get the vaccine, because I still do not have any plans to get married. There is no use to get vaccinated if you are not getting married. I may consider getting vaccinated if I am going to get married. [Participant 24]Non-vaccinated participants perceived the plan of getting married as remarkable to make the vaccine worthy for them. The perceived worthiness of the HPV vaccine was also related to the perceptions of participants about its protective value:I know the vaccine can prevent cervical cancer. However, I also know that there [the vaccine] is no 100% guarantee [for the efficacy]. I still have the chance of getting cervical cancer even after getting vaccinated. Then what is the point in spending such a large sum of money for a vaccine that cannot provide full protection to me? [Participant 25]The cost of the vaccine appeared to be a remarkable factor in the decision-making process. However, in addition to the actual monetary value of the vaccine, cost consideration was also based on the perceived worthiness of the vaccine, which was majorly influenced by the risk perception of developing cervical cancer—related to marriage plans in most circumstances—and/or other HPV-associated conditions as well as the perceived protective value of the vaccine.Sexual experiences and frequency of sexual activities were closely related to the perceptions of participants about the worthiness of getting vaccinated for HPV and thus played a role in their decision-making process. The more their sexual experiences and frequency of sexual activities, the higher was the perceived risk of having cervical cancer. With regard to the understanding of participants, HPV-related risk implied the risk of having cervical cancer, not other HPV-associated conditions. The following perceptions were frequently mentioned in the interviews:The advertisement said that all women need the vaccine … But as I know, this virus is sexually transmitted, so I think only those who have many sexual partners and frequent sexual activities are at a higher risk … I don’t think I am at a high risk; I am not that kind of person, so I don’t think I need the vaccine. [Participant 7]Sex is a way of transmitting HPV. If people engage in sexual activities more and if they have many sexual partners, they will have a higher chance of getting the virus and related diseases for sure. Also, sex can hurt the womb. More sex more harm … For those who do not indulge in sexual activities often or have just one sexual partner, I do not think they need the vaccine. [Participant 25]Hence, participants believed that there exists a close relationship between sexual activities and cervical cancer incidence. Most participants had the perceptions that HPV, and thus cervical cancer, is sexually transmitted. They commonly possessed a stereotype of being promiscuous, which, as per the participants, referred to having more than one sexual partner and indulging in frequent sexual activities. This in turn would be harmful to the uterus, increasing the chances of developing cervical cancer. As all non-vaccinated participants expressed that they were either abstinent or only engaged in sexual activities with one stable partner, they perceived themselves as being at a low risk of cervical cancer; consequently, they believed that there was no real need of being vaccinated for HPV.When I was about to take the first dose, the nurse said that the efficacy of the vaccine is better for those who have never had any sexual experience. As I have had no sexual experiences, I think I can get the most from the vaccine and the vaccine is worthy. However, some of my friends, after whispering to one another, decided not to get the vaccine; I guess they must have had sex before, and getting the jab would be a waste. [Participant 1]The pattern and frequency of sexual activities were thus interlinked with the perceived worthiness of getting vaccinated for HPV; these were the other key determinants affecting the decision-making process. The perceptions about sexual activities in relation to HPV vaccines as possessed by the participants, however, were to some extent contradictory. On one hand, having no sexual experience was believed to enhance the efficacy of HPV vaccine, whereas on the other, no sexual experience also reduces the risk of getting cervical cancer and thus the perceived need of getting vaccinated.Sexual experiences were a key determining factor in the decision-making process. The participants believed that sexual experiences affect the efficacy of HPV vaccine, and this discouraged them to get vaccinated:Irregular menstruation is a symptom showing that the uterus is weak. This indicates that the uterus is not strong enough to fight against the disease [cervical cancer]. Therefore, it is better to get vaccinated if you have menstruation problems. [Participant 40]The presence of gynecological conditions in the family and social network of participants was also closely related to their awareness and perceived risk of getting cervical cancer—such a presence motivated them to think about getting vaccinated:Having uterus-related problems is not rare in my family. I have three elder sisters and two of them suffer from [uterine] fibroids. Their daughters have [uterine] fibroids as well … We [my sisters and nieces] all concern about our uteruses, so we used to talk about the [HPV] vaccine. We have been thinking if the [HPV] vaccine can provide more protection to us … My sisters [who suffer from uterine fibroids] have had their uterus removed already, and my nieces got the [HPV] vaccine soon afterwards [after we have discussed the efficacy of the vaccine], hoping that the vaccine can provide more protection to them. [Participant 26]Besides the family members of participants, the experience of people getting cancer, particularly cervical cancer, in their social network also enhanced their awareness of HPV vaccination. Such experiences by those in their social network familiarized participants with cervical cancer, serving as a determinant in their decision-making process:I did not take the cervical cancer vaccine in the past. However, many of my friends have been suffering from cervical cancer in recent years. I know them, and I know they are well-behaved and have led a healthy lifestyle. I did not expect them to have cervical cancer. My friends’ experiences have motivated me to take the vaccine now, because cervical cancer can happen to good women as well. [Participant 9]However, in a few cases, the experiences of family members and those in the social network also had a negative influence on the decision-making process of a few participants, which in turn reduced their motivation to get vaccinated:Everyone can have cancer in any part of the body … so there is no need to take any special preventive measures against cervical cancer. To prevent cervical cancer, or I should say all types of cancer, I still believe we should use a more holistic approach to enhance our health … I live in a healthy way, so I don’t think I need the [HPV] vaccine. If I have been leading a healthy lifestyle but still I get that cancer [cervical cancer], then that is fate. You can do nothing to change your fate; even if you can save yourself from cervical cancer by getting vaccinated, you will still suffer from other cancers. [Participant 29]In contrast, the absence of gynecological conditions in the family and social network of participants, particularly in case of non-vaccinated participants, resulted in unawareness among them regarding the risk of cervical cancer and the need of getting vaccinated:I don’t think I am at a high risk of getting cervical cancer … None of my family members have cervical cancer, so I suppose I also have a very low chance of having it. Therefore, I don’t think I need to get vaccinated. [Participant 3]Thus, the decision-making process regarding HPV vaccination was influenced if participants themselves or people in their social network experienced gynecological conditions. Such experiences familiarized participants with cervical cancer, enhancing their awareness and perceived risk of cervical cancer, and eventually their motivation to get vaccinated.Another factor influencing the decision-making process was the history of experiencing gynecological conditions. Participants with a history of cancer or other physical conditions that are exclusively observed in women were noted to have a higher perceived need of getting vaccinated for HPV. For such participants, the nature of gynecological conditions, such as menstruation-related conditions, was similar to cervical cancer. They often interpreted gynecological conditions as the insufficiency of the uterus, and such “uterus insufficiency” enhanced their sense of awareness and vulnerability toward cervical cancer, remarkably affecting their decision-making process and serving as a motivation to get vaccinated:I chose that one [vaccine] with Ah Sa [female celebrity] as the spokesperson, because the clinic provided more information about that vaccine than the other one [vaccine] with GEM as the spokesperson. [Participant 5]On the other hand, difficulty in obtaining information and confusing information discouraged participants:I have been thinking about taking the vaccine. There are 9-in-1, 6-in-1, and 4-in-1 vaccines, but the information on these vaccines is rare and too confusing. I don’t really know the concrete difference among the three vaccines, and it is difficult to obtain more information. I think I will need to obtain more information before I can decide whether I would want to get vaccinated, and if so, which one I would choose. I don’t know where to get more information, so it is difficult for me to decide. [Participant 14]The efficacy and side effects of HPV vaccine were the most needed information that could influence the decision-making process of participants. Merely knowing its efficacy against cervical cancer was far from adequate for most participants. Rather, the eligibility to get vaccinated, duration of efficacy, and conditions that the vaccine could prevent were key insights that participants sought; such information was however seldom available:I know that the cervical cancer vaccine can prevent against cervical cancer, but I do not know if it is okay for me to get the jab. I suspect I am too old to get it. [She was 56 years old.] I have tried to search for the answer but failed. What I know is that there is a vaccine called cervical cancer vaccine from the leaflets and bulletins that I got from clinics, hospitals, or even from The Family Planning Association of Hong Kong [a non-government organization in Hong Kong providing medical and counselling service in sexual and reproductive health]. That’s all what I know about this vaccine. No one has told me whether I am eligible to get the jab. [Participant 36]The acquisition of information on HPV vaccines was crucial to the decision-making process. Sufficient information regarding the vaccine apparently served as an important motivation factor for most participants:Indeed, I want to ask the doctor about the cervical cancer vaccine. However, the consultation is too rushed. There is no time for me to ask any questions. Similar to most typical consultation scenarios that you can imagine, the doctor just asked me when I got sick and the symptoms, and then simply gave me some medicines and asked me to leave. [Participant 8]Lack of explanation by healthcare providers also served as a barrier:I have asked the doctor once in the past whether I need to get the jab. He responded by asking me how old I was, and then he said I didn’t need the jab. That’s all! The doctor didn’t explain anything to me. Is it because I am too old for the vaccine or could there be other reasons? I have no idea because the doctor did not explain anything. [Participant 17]Consultation with doctors in Hong Kong primarily involves discussions on curative and treatment methods, rather than on preventive measures. People visit doctors mainly when they are sick. Doctors thus do not show much enthusiasm in dealing with inquiries pertaining to vaccines. Moreover, several participants fail to realize that can in fact discuss issues pertaining to vaccination with doctors:I have many questions about the vaccine, but didn’t realize that I could ask my doctor. When you go to see a doctor, you are sick. Therefore, I don’t want to be in the clinic for long. I just want to see the doctor for my sickness, have it dealt with, and then leave as soon as possible. I have never thought of asking doctors about vaccines, because I go to them for getting treated, not for discussing vaccination. [Participant 25]Vaccination is a preventive intervention. In the typical clinical practice in Hong Kong, it is unusual for patients and doctors to discuss preventive care, such as vaccination, within the premises of consultation. A few participants still did mention that their doctors suggested them to get vaccinated against HPV as part of consultation; this however made participants suspicious of the intention of their doctors:The doctor has never mentioned this issue [HPV vaccination] in the past consultations. I didn’t ask him. However, he suddenly suggested the vaccine to me … I was a bit shocked and wondered if he wanted to make more money by selling the vaccine to me. [Participant 28]Although some participants already had an established relationship with their doctors, the suggestion of vaccination, in most cases, made them suspicious of the intention of their doctors:My gynecologist had suggested me to take the vaccination. However, I do not think I have any such need because the pap smear result was normal at that time, so why do I need to take the vaccine? After the doctor informed me that my pap smear result was normal, he then went on to ask me if I wanted to take the jab. His tone, facial expression, and gesture were quite suspicious to me. He smiled maliciously, making it seem as if he was selling the vaccine to me rather than giving professional advice. [Participant 36]HPV vaccines in Hong Kong are mostly available on a self-pay basis and administered by private practice doctors. As preventive care is not a clinical norm in Hong Kong, doctors suggesting vaccination to patients is sort of exceptional; such advice can in fact lead to doubt and suspicion among patients. Also, as stated by participants, they had no intention to ask their doctors about getting vaccinated because the stereotypical linkage among doctors, sickness, and treatment is much stronger than the linkage between doctors and preventive care. Thus, if vaccination was recommended by doctors, participants became suspicious and assumed that doctors had commercial intentions. Such social norms in clinical practice thus negatively influenced the decision-making process of participants.Few participants had attempted to seek more information about the vaccine from their doctors, but they often failed to obtain any robust information. This negatively influenced their decision-making process:If it is an important vaccine for women, why doesn’t the government enforce all women to take it? Yes, if the government takes a more active role in promoting the cervical cancer vaccine, I will think it [vaccination] is important and urgent. [Participant 32]From an overall perspective, information pertaining to HPV vaccination was a significant factor facilitating the decision-making process. However, the information had to be perceived as trustable and credible. Unfortunately, such information was limited, constraining the decision-making process of participants.The standpoint of government health authorities about HPV vaccines, on the other hand, had a remarkable positive influence on the decision-making process. Participants perceived the information provided by the government as more credible and reliable than that provided by their doctors:The moral standard in our society is not good already. I feel some girls may think that being vaccinated will allow them to have sex more freely and openly. They would think they can do whatever they want after getting vaccinated. I think this is not good. Education is needed for these girls to have a correct attitude toward sex. They won’t care about these [moral] issues if they know that they are totally safe from cervical cancer after the vaccination. [Participant 23]Consequently, some participants were not in the favor of getting vaccinated:Probably one of the negative consequences of promoting cervical cancer vaccination is that girls may think that “I won’t get cervical cancer anymore,” so they have nothing to fear and may have casual sex with others more freely. [Participant 26]Thus, HPV vaccine was perceived as a facilitating agent that could encourage immoral, promiscuous, and unsafe sexual behaviour in vaccinated women, as they would no longer fear cervical cancer. This perception also represents a stereotype in vaccinated women who are to be perceived as violators of the moral value system. Such perception indicates that the cultural meanings of immorality and promiscuity in the context of HPV vaccines influence the decision-making process of participants. Such a cultural stereotype did not merely influence the need to get vaccinated, but it also intensified the moral burden on those who did get vaccinated.Promiscuity was commonly perceived by participants as an important cause of cervical cancer. They believed that everyone did not need HPV vaccination; rather, sex workers and promiscuous people with more than one sexual partners were perceived as having a higher need to get vaccinated. Considering the stereotypical relationship between cervical cancer and sexual activity, getting vaccinated for HPV was beyond a health issue to participants—it was more of a moral issue to them:I have read some news on the Internet reporting the serious side-effects of getting vaccinated. I’m really worried if the vaccine is safe or not, so I still have not made up my mind. I want to wait to see if there are any side-effects being reported … I cannot remember [the side-effects] exactly. I just have heard that some people died after getting vaccinated, while others have gotten paralyzed. I remember these side-effects happened overseas, but they sound horrible, so I dare not get the vaccine … I think the news is trustable. After all, I do not think doctors or drug companies [pharmaceutical companies] will inform you of these side-effects because they are selling the vaccine. [Participant 37]Most participants were not exactly aware of the side-effects of HPV vaccines; they still stereotyped the vaccine as being able to cause death and paralysis.Our study participants were also majorly concerned about the side-effects of HPV vaccine. Some were worried because of the first-hand experiences of people in their social network, but most were worried due to news reports on the side-effects of HPV vaccines, which they often obtained from the Internet. Such news reports remarkably served as a barrier and negatively influenced the decision-making process:As demonstrated by our study participants, the following factors intertwined to influence their decision-making process: perceptions of HPV and HPV vaccine; perceived worthiness of HPV vaccine, which was affected by its cost, marriage plans, and experiences of sexual activities; history of experiencing gynecological conditions; stigma associated with HPV vaccination; acquisition of information on HPV vaccines; distrust on HPV vaccines; and absence of preventive care in the healthcare practice. These factors involve the complex and interlocking relationship of the four social levels.In sociology, meanings are embedded in the institutional fabric of society, so reality, or more specifically the understanding of reality, is recognized as a result of social processes of meaning construction and interpretation . What peHPV vaccination is an effective preventive measure against cervical cancer. In addition, HPV vaccine can prevent other types of anogenital cancers and other HPV-associated conditions such as genital warts. Genital warts are indeed the commonest outcome of HPV infection . In the According to the Sapir–Whorf hypothesis, language and vocabulary can influence our perceptions . The “reSocial constructionism purports that the so-called reality is maintained by social and cultural systems, with its embodiment embedded in the continuing human activities and communication among people , 36, 59.Gender studies have indicated that differences between men and women not only pertain to biological sexual differences but also to hierarchical differences in terms of intuitive, ontological security, and power . Gender Feminization of HPV vaccines is also seen in the United States and causes different negative consequences to health promotion for both women and men, resulting in overburdening of women for screening and treatment of HPV-associated conditions and reduced protection from HPV-related illnesses for men . In our The complex moral implication of HPV vaccine served as another key determinant affecting the participants’ decision-making process. Following the argument of Sapir–Whorf hypothesis, the confusion between HPV and HIV led participants to have a stereotypical perception about the interrelationship between HPV, AIDS, cervical cancer, and immoral sexual activities. Such a perception served as an influential element in the decision-making process regarding HPV (non) vaccination, particularly for those were not vaccinated.HPV was perceived by our participants to be sexually transmitted. Cervical cancer was consequently stereotyped as a condition mostly affecting sexually active and promiscuous women. HPV vaccine, thus, was perceived to be most needed by women who engaged in promiscuous and frequent sexual activities, serving as a subtle encouragement for having casual and immoral sexual behaviour, both of which are regarded as cultural taboos in Hong Kong. This stereotype contributed to a low perceived risk among participants due to their perceived moral sexual behaviour, which thereby led to their low perceived needs of getting vaccinated.Advice from medical institutions embedded in the patriarchal value system also played a remarkable role in influencing the reputation of HPV vaccines. The vaccine has been presented as having the strongest efficacy for women without any sexual experiences . In our Such accentuation demonstrated the contradicting symbolic meaning of HPV vaccine. The power of cultural stereotype and stigma associated with HPV vaccination prevented participants from getting vaccinated, serving as a social control for women. Women are not only being culturally controlled for their  behaviours but also being deprived of having the rights to proactively protect their health, leading to their limited accessibility and health inequality in pursuing this preventive health behaviour. The cultural stereotype and stigma associated with HPV vaccination were remarkable elements that influenced the decision-making process, particularly in case of non-vaccinated participants.Participants were also reluctant to receive HPV vaccination considering the weaknesses of the macro-healthcare system and problematic doctor–patient relationship, which in turn affected their decision-making process. A recent study  investigThe healthcare system of Hong Kong follows a “dual-track system,” encompassing both the public and private sectors. While the former provides a “safety net for the entire community,” the latter offers “personalized choices and more accessible services to those who are willing and may afford to pay for private healthcare services” . Such a The healthcare structure of Hong Kong driven by “mixed-economy” and capitalism plays a remarkable role in influencing the perception of people regarding doctors, restraining the acquisition of information on vaccination and impacting their trust on doctors and the vaccine. There reportedly exists an embedded distrust on the private healthcare system and private practice doctors ; we alsoThe lack of the family doctor system in Hong Kong is also responsible for the lack of trust between doctors and patients, making preventive care at the primary care level, such as advice regarding vaccination, difficult. As majority of the primary care service is provided by the private healthcare system in Hong Kong , distrusOur participants widely perceived government health authorities to be the most trustable and credible sources of information on HPV vaccines. This finding was consistent with the past literature, indicating that people in Hong Kong have a higher trust on public than on private healthcare as there is no association between public healthcare and business . HoweverOur findings indicate that the decision-making process regarding whether to receive HPV vaccination is a complex one, involving interlinked factors. Based on the education level and socioeconomic status of participants, financial factors were a less important determinant affecting the decision-making process. However, this does not imply that vaccine cost was irrelevant; the decision of HPV vaccination was affected by the assessment of worthiness of the vaccine, which in turn was affected by diverse perceptual, social, cultural, and structural factors, rather than simply the monetary cost.Our study findings also somewhat consistent with the concept of vaccine hesitancy , as we rAs we mostly sampled women from a local university and a primary care clinic located in a middle-income district with a relatively high percentage of population with postsecondary education, hence our findings mostly reflect the perceptions and decision-making process of women who belong to a relatively high socioeconomic status. A more holistic view can be achieved by sampling women belonging to a low socioeconomic status and from different field sites. However, our sampling type allowed us to gain an in-depth understanding of the complex perceptual, social, and cultural issues that influence the decision-making process in women, apart from the financial concerns related to HPV vaccination.This study, from perceptual, social, cultural, and structural aspects, discusses the interlinked factors that influence the decision-making process regarding HPV vaccination in women in Hong Kong. The promotion of HPV vaccination is “feminized” and “moralized,” which consequently influenced the understanding of our study participants regarding HPV vaccination, and limited their accessibility of vaccination as preventive health behaviour. Health inequality in accessing HPV vaccine has thus been resulted. The “mixed-economy” medical system of Hong Kong driven by capitalist logic also makes preventive care absent in the consultation process between patients and doctors, molding a weak doctor–patient relationship, making the implementation of advice from private practice doctors regarding vaccination even more difficult. The government health authorities, therefore, should take more proactive action in promoting HPV vaccination considering the trust from public.


The aim of this study is to assess whether 3q26 gain as a single genetic marker can predict the natural prognosis of high-grade CIN, by performing a review of the literature and pilot study. A literature review was conducted. Additionally, we performed a pilot study in 19 patients with histologically confirmed high-grade CIN lesions who were followed for a mean of 115 days, after which loop excision was performed. Fluorescent in situ hybridization analysis was performed on the initial diagnostic biopsies to determine gain of 3q26. Eight studies were included in the literature overview, with a total of 407 patients. Of these, only 22 patients had high-grade lesions. All studies found an association between 3q26 gain and disease prognosis. Positive predictive values (PPV) ranged from 50 to 93%, negative predictive values (NPV) ranged from 75 to 100%. Only five out of 155 patients (3.2%) without 3q26 gain showed disease persistence or progression. In our pilot study on 3q26 gain in high-grade CIN, the PPV of 3q26 gain for disease persistence was 67%, the NPV 100%. All four patients without 3q26 gain showed disease regression. In conclusion, the absence of 3q26 gain in diagnostic biopsies may be applied to identify high-grade CIN lesions with a high probability of disease regression.Approximately 20–40% of high-grade Cervical Intraepithelial Neoplasia (CIN) regresses spontaneously, but the natural prognosis of an individual lesion is unpredictable. Gain of the chromosomal 3q region, which contains the human telomerase RNA gene on  High-grade Cervical Intraepithelial Neoplasia (CIN) is caused by Human Papillomavirus (HPV)-infection and is considered to be the precursor of cervical carcinoma . ApproxihTERC), which is localized on the 3q26 locus. The hTERC gene encodes for the RNA unit of telomerase, which maintains the length of telomeres through cellular divisions. Overexpression of hTERC leads to the avoidance of abnormal cells with critically short telomeres to undergo apoptosis, which is a contributing factor in oncogenesis. Gain of 3q26/hTERC or copy number variations has been shown to correlate with disease grade in cervical lesions and could function as a diagnostic tool in cervical pathology [3q26/hTERC gain in the natural prognosis of CIN, but most studies focussed on low-grade lesions and/or evaluated 3q gain in cytological specimen. Evidence on 3q gain in histologically confirmed high-grade CIN is very scarce. The goal of this study is to provide an overview of the literature on the prognostic properties of 3q26/hTERC gain in the natural prognosis of CIN and to investigate the predictive properties of 3q26 gain specifically in high-grade CIN.It has been established that the development of CIN and concurrent progression to cervical cancer is influenced by a complex interaction between HPV, the host immune system and functional cellular mechanisms , 9. Cervathology –16. SeveThe study was performed according to the PROBE criteria for biomarker research, where possible and applicable.3q26 analysis was available for 19 patients. These patients were included in the pilot study.For the pilot study, the patient population was extracted from a prospective population based cohort study, conducted at the Stavanger University Hospital, Norway . The wom3q26 probe , were labeled with Digoxigenin (3c) and Biotin (3q) in a nick translation labelling . The probes were hybridized at a concentration of 2 ηg/μl (3c), 5 ηg/μl (3q); 10 x excess COT, and 75x excess of carrier DNA  in 50% formamide; 2x SSC; 10% dextran sulphate. The probe was applied under a coverslip, simultaneously denatured for 10 min at 80 °C and hybridized overnight at 37 °C. After hybridization, the preparations were washed for 5 min at 61 °C in a solution, containing 2 × SSC, 0.05% tween-20  and 0.1 × SSC (the washing was carried out twice). The hybridized FISH probe was detected with a triple layer detection method, consisting of 1. FITC-conjugated avidin  / Monoclonal anti-Digoxigenin ; 2. Botinylated Goat anti-Avidin  / Rabbit anti Mouse-TRITC  and 3. Av-FITC / Swine anti Rabbit-TRITC (1:100 dilutionDako). Finally, the slides were washed in PBS containing 0.05% Tween-20, dehydrated in an ascending ethanol series and mounted in Vectashield (Vector Laboratories), containing DAPI (Sigma: 0.5 μg/μl). Images were recorded with the Metasystems Image Pro System , mounted on top of a Leica DM-RE fluorescence microscope [FISH analysis was performed on the baseline biopsies. The 3q specific FISH was performed on 4 μm thick FFPE tissue sections fixed onto Superfrost Plus Microscope Slides (Thermo Fisher Scientific). The tissue sections were first heated for 15 min at 80 °C, then dewaxed, hydrated and microwaved for 10 min at 100 °C in a 10 mM Na-Citrate pH buffer and incubated at room temperature for 20 min to cool down. Subsequently, the sections were washed in demineralized water, rinsed in 0.01 M HCl and digested with 2.5 mg of pepsin in 0.01 N HCl and post-fixed in 1% formaldehyde in PBS for 5 min at room temperature. Subsequently, the 3 centromere probe (pα3.5) and The FISH signals were interpreted by two analysts , who were blinded to the outcome data. Dysplastic areas were identified based on p16 staining and were scanned for FITC and TRITC signal copy numbers. The copy number was estimated as previously described to detect disomy, tetrasomy up to nonasomy by means of the determination of the maximum copy number and heterogeneity in formalin fixed and paraffin embedded tissue sections. The validity of this strategy was independently proven by means of a statistical analysis of spot counting in tissue sections , 18. Les3q26 gain and disease persistence of high-grade CIN. No previous biomarker performance values are available for HLA types. The required test performance values include a high sensitivity and negative predictive value: lesions that will not regress spontaneously must be identified, as treatment is necessary in these women. The actual values depend on the follow-up term of observational management. Lower values can be accepted when strict histological follow-up is implemented to identify persisting lesions at an early stage.The outcome measure was defined as the correlation between Quantitative variables were described as mean and ranges. Qualitative variables were described as frequency and percentage. Sensitivity, specificity, positive and negative predictive values were calculated from a 2 × 2 table. Sample size calculation was not feasible, due to the lack of comparable biomarker performance values and limitation of the study population by the availability of material.3q26/hTERC gain in cervical squamous lesions [Eight studies were identified that evaluated the predictive properties of  lesions –26. All  lesions . Ravaiol3q26 gain showed disease persistence or progression.The main study results are summarized in Table 3q26/hTERC gain as a potential prognostic marker in cervical precancerous lesions. 3q26/hTERC gain seems more frequent in persistent or progressive lesions, but positive predictive values are generally low: patients with 3q26/hTERC gain often show disease regression during follow-up. Negative predictive values are consistently higher: absence of 3q26/hTERC gain seems to be a strong predictor of disease regression.All studies identify 3q26/hTERC gain in high-grade lesions. The baseline diagnosis was not determined uniformly: some studies included patients based on cytology, whereas others included only histologically confirmed lesions. Furthermore, follow-up periods and methods differed: both cytology and histology was applied. Regarding the FISH analysis, the different studies did not apply a similar signal interpretation method and threshold for gain. Another important limitation in the interpretation of the study results is that HPV testing was not performed or reported in most studies. It is therefore unclear whether all lesions were HPV-induced. This limits the applicability of the study results to high-grade lesions, which are usually HPV positive. Moreover, HPV genotype is an individual predictor in the natural history of CIN lesions. As such, information on HPV status would improve the interpretation of the study data.Nevertheless, several limitations of the individual studies and their review must be noted. Patient populations were generally small. Most studies included only patients with low-grade lesions, which limits the evidence on the prognostic properties of 3q26/hTERC analysis has been consistently identified as a prognostic marker in cervical precancerous lesions, with a high negative predictive value in mostly low-grade lesions. As such, evidence indicates a potential predictive role of 3q26/hTERC gain in the natural prognosis of cervical dysplasia, but clinical applicability is yet limited and the evidence on the predictive properties of 3q26/hTERC gain in histologically confirmed high-grade lesions is scarce (n = 5). This prompted us to perform a pilot study evaluating the predictive properties of 3q26/hTERC gain in histologically confirmed high-grade lesions.Despite all limitations, A total of 19 women were included in our study. The mean age was 31 years (range 25–41). The mean interval between the initial colposcopy and the follow-up colposcopy with LEEP was 115 days (91–154 days). Nine women (47%) showed disease regression during this follow-up period and ten did not (53%). The mean age and biopsy-LEEP interval did not differ significantly between women who showed spontaneous regression and those who did not .p = 0.5). In the original study, lesions were classified according to size in two categories: larger than 2.5 mm or equal to or smaller than 2.5 mm. There was no difference between these two categories in terms of the number of women with and without regression: a lesion larger than 2.5 mm was found in 5/9 (56%) women with disease regression and in 7/10 (70%) women with disease persistence (p = 0.54). All women carried high-risk HPV. HPV-16 was found in 5/9 (56%) women with disease regression and 7/10 (70%) women with disease persistence (p = 0.54). The biopsy material of all cases was p16 positive, confirming HPV infection.Sixteen patients were diagnosed with a CIN3 lesion and three with a CIN2 lesion. Of the patients with a CIN2 lesion, two showed regression and one showed disease persistence  and gain of hTERC are important associated genetic events in the progression of CIN to cervical cancer [3q26/hTERC. Furthermore, future studies should clarify the association between HPV genotype and 3q gain, with regard to the natural prognosis of high-grade CIN.Only five out of eight reviewed studies performed HPV typing, of which only one study reported on the association between HPV and 3q gain: a non-significant association was found between viral load and 3q gain . As discl cancer . On the l cancer . AssessmLimitations of the current clinical study include the small patient population. The patient population was extracted from a historical cohort of patients from a previous study, based upon the availability of sufficient biopsy material. Another limitation of our study may be the use of histological specimen instead of cytology for the FISH analysis, which has been shown to be more sensitive to the identification of cells with 3q gain , 19. We 3q26 gain could potentially serve as a prognostic biomarker for the identification of CIN lesions with a high probability of disease regression, preferentially as part of a broader biomarker profile. As such, 3q26 staining could aid in the selection of women with low-grade lesions who would not need immediate colposcopic assessment and women with high-grade lesions who would not need immediate treatment. Both strategies could result in reduced costs, patient burden and side effects of surgical treatment. To confirm this hypothesis further research is necessary. Research should focus on identification of a generalized methodology for 3q26 gain testing and interpretation. Subsequently, its prognostic properties should be confirmed in a larger patient population. Moreover, assessment of the association between HPV and 3q26 gain is needed. Upon confirmation of its prognostic properties, 3q26 staining could be considered as part of a biomarker profile to triage women with high-grade lesions for conservative follow-up measures.In conclusion, the results of the current review and pilot study show that the absence of


Given the paucity of data and widely variable rates that have been reported, the main objective of this study was to examine the prevalence of HPV-positivity in oropharyngeal squamous cell carcinoma (OPSCC) in Middle Eastern patients presenting to one of the region’s largest tertiary care centers using polymerase chain reaction (PCR) amplification of the HPV E6/E7 oncogenes, a highly sensitive and specific method of detection.Medical charts and archived pathological specimens were obtained for patients diagnosed with biopsy proven oropharyngeal cancer who presented to the American University of Beirut Medical Center between 1972 and 2017. DNA was extracted from paraffin-embedded specimens and tested for 30 high-risk and low-risk papilloma viruses using the PCR-based EUROarray HPV kit (EuroImmun).A total of 57 patients with oropharyngeal cancer were initially identified; only 34 met inclusion/exclusion criteria and were included in the present study. Most patients were males (73.5%) from Lebanon (79.4%). The most common primary tumor site was in the base of tongue (50%), followed by the tonsil (41.2%). The majority of patients (85.3%) tested positive for HPV DNA.The prevalence of HPV-positivity amongst Middle Eastern OPSCC patients, specifically those from Lebanon, may be far greater than previously thought. The Lebanese population and other neighboring Middle Eastern countries may require a more vigilant approach towards HPV detection and awareness. On an international level, further research is required to better elucidate non-classical mechanisms of HPV exposure and transmission. Human papillomavirus (HPV) is well-established as a distinct etiological risk factor for oropharyngeal cancer . SeveralPatients with HPV-related OPSCC are reportedly more likely to be younger, white, male, married, and college-educated than their HPV-negative counterparts . AdditioThe prevalence of HPV-related OPSCC appears to differ widely by region, potentially owing to differences in social practices attributed to different cultures around the world. Data regarding the prevalence of HPV-related OPSCC in the Middle East region in particular is scarce. Given the paucity of data and widely variable rates that have been reported, the main objective of this study was to examine the prevalence of HPV-positivity in OPSCC in Middle Eastern patients presenting to one of the region’s largest tertiary care centers using polymerase chain reaction (PCR) amplification of the HPV E6/E7 oncogenes, a highly sensitive and specific method of detection. Secondary outcomes included investigating the impact of HPV tumor status on prognosis in this cohort, specifically overall survival and recurrence-free survival.This study was reviewed and approved by the Institutional Review Board at the American University of Beirut (AUB) in Beirut, Lebanon.International Classification of Diseases 9 (ICD-9) codes 141.0 Malignant neoplasm of base of tongue and 146.x Malignant neoplasm of oropharynx . Medical charts were retrieved from the medical records department and archived pathological specimens were obtained from the pathology department when available. Verbal consent was obtained over the telephone from living patients. No consent was obtained for the inclusion of deceased patients as this was considered non-human subject research.Patients diagnosed with biopsy proven oropharyngeal cancer who presented to our institution between 1972 and 2017 were identified according to the Patients of all ages and both genders with the following criteria were included: primary lesions of the oropharynx and its subsites, specifically the palatine tonsils, base of tongue, soft palate, posterior oropharyngeal wall, anterior pillars, posterior pillars, and valleculae; primary lesions of the oropharynx with extension to neighboring/distant sites or metastasis; patients originating from Middle Eastern countries.The following were considered as exclusion criteria: patients with metastatic disease from distant sites to the head and neck; patients with non-oropharyngeal head and neck cancers; patients with non-squamous cell tumors; patients who did not have any records or pathological specimens available at our institution.A retrospective chart review was performed whereby demographic and clinical data were obtained regarding age at diagnosis, gender, country of origin, history of tobacco and alcohol use, site of primary tumor, TNM classification, stage at presentation, and modality of treatment including surgery (resection +/− neck dissection), radiation therapy and systemic therapy (chemotherapy or cetuximab). Tobacco use was defined as a smoking history of ten pack years or greater, where one pack is equivalent to smoking 20 cigarettes, and a pack year is defined as the number of packs smoked per day multiplied by the number of years the person has smoked. TNM classification and staging information were retrieved directly from medical charts or inferred from clinical records and imaging reports according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 7th edition. Survival data was obtained, including status at last available follow-up regarding recurrence and death, up until five years from diagnosis. No patient identifiers were collected. Pathological specimens, including paraffin-embedded biopsy and surgical tissues, and cryopreserved fine-needle aspirates, were retrieved, coded and de-identified.DNA was extracted from all samples using Qiagen reagents. DNA aliquot was then tested using EUROarray HPV kit (EuroImmun). The test is designed for molecular diagnostic in vitro detection and typing of 30 human anogenital high-risk and low-risk papilloma viruses  from DNA preparations. The test system is based on detection of the viral oncogenes E6/E7. In the first reaction step, regions of the viral oncogenes E6 and E7 from HPV that are present in the sample are amplified and fluorescently labelled by means of PCR using a multiplex primer system. In the second reaction step the products are detected using an oligonucleotide microarray. The specific binding (hybridization) of a fluorescing PCR product to the corresponding oligonucleotide probe is detected using a special Microarray Scanner (EUROIMMUN). The EUROArrayScan (EuroImmun) software evaluates all spot signals and generates the test results. An additional primer system that amplifies a region of human genomic DNA is integrated into the test system. This serves as a positive control for the DNA preparation. Correctly taken smears will contain cervical cells and hence their genomic DNA.p-value less than 0.05 was considered statistically significant. Kaplan-Meier analysis with the Log rank test was used to conduct unadjusted survival analysis for overall and recurrence-free survival with time-to-outcome calculated starting at the date of diagnosis. Censoring for subjects with no reportable events was performed at date of last follow-up. All statistical analyses were performed using SPSS Statistics for Windows Version 25.0 .Associations between HPV status, and demographic and clinical characteristics were assessed using the Mann-Whitney U Test for continuous variables and Fisher’s exact test for categorical variables. A two-sided A total of 57 patients with oropharyngeal cancer was initially identified; only 34 met the above cited criteria and were included in the present study. Demographic and clinical characteristics for all patients were stratified by HPV status and are summarized in Table The majority of patients  tested positive for HPV DNA. There were no statistically significant differences regarding any demographic or clinical variables when comparing HPV positive and HPV negative groups. In particular, all 5 HPV negative patients originated from Lebanon. Out of 8 nonsmokers, 7 were HPV positive. The majority of HPV positive patients presented with advanced nodal disease . Only 4 HPV positive patients presented with distant metastasis. Interestingly, all 3 soft palate tumors tested positive for HPV DNA.Figure p = 0.125) or recurrence-free survival (Log rank p = 0.941) between HPV negative and HPV positive groups. Mean overall survival for the HPV positive group was 56.5 ± 3.4 months, and mean recurrence-free survival was 42.8 ± 5.4 months.Overall and recurrence-free survival data were available for 24 and 23 patients, respectively. There was no significant difference in overall (Log rank The prevalence of HPV-related OPSCC in our study sample was found to be 85.3%, which is comparable to the higher rates reported in many developed countries –5, 10. TWhile the largest number of studies on HPV-related OPSCC may have been conducted in North America and Europe, there is a multitude of studies performed around the world that echoes the importance of HPV in the development of OPSCC. A meta-analysis examining HPV-related OPSCC trends by region over time between 1970 and 2008 found that rates in North America increased from 50.7 to 69.7%, and those in Europe increased from 35.3 to 73.1% . One stuOral-genital and oral-oral contact has been implicated in the transmission of oral HPV infection and subsequent development of OPSCC . There iThere are over 200 subtypes of HPV that have been identified. The carcinogenic potential of high risk subtypes such as HPV-16, the most commonly isolated subtype from the oropharynx, was first established in cervical cancer . Other hMultiple methods for HPV detection in patient tumor samples have been described and are utilized in daily practice. The most prevalent method to date, owing to its cost-effectiveness, ease of interpretation, and high sensitivity, is IHC for p16 as a surrogate marker of HPV positivity . HoweverAs most of the patients in our study are Lebanese, the potential implications of these findings most strongly apply to the Lebanese population. An important aspect of our study will be its impact on health education and on raising awareness about HPV-related OPSCC, which could play a role in controlling the increasing prevalence of this entity and promoting vaccination among young adults. With the advent of vaccines for prevention of HPV-related cervical cancer, the incidence of HPV-related OPSCC might decrease with the decrease of HPV-positivity and transmission as a whole . HoweverOur study has some limitations, primarily owing to its retrospective nature. Because of the relatively low incidence of OPSCC in our population in general, we were required to obtain medical records spanning a somewhat large timeframe. As a result, the quality of the records obtained differed greatly depending on when the record was originally created. We were not able to obtain adequate survival data to completely analyze our secondary outcomes, due to the low number of HPV-negative patients and the high number of censored subjects. Additionally, we were only able to include patients who had either a biopsy or resected specimen available at our institution. Due to our utilization of a DNA based PCR detection method, we are not able to make definitive conclusions regarding genomic integration or disease association. However, the prevalence of high-risk HPV subtypes amongst our OPSCC specimens itself is impressive. Finally, as OPSCC is uncommon in our country, our sample size was low; however, this will be the subject of future studies.We have demonstrated that the prevalence of HPV-positivity amongst Middle Eastern OPSCC patients, specifically those from Lebanon, may be far greater than previously thought. The implications of this are many, as HPV-related OPSCC behaves much differently than HPV-negative OPSCC both clinically and prognostically, and often may benefit from a different approach to treatment. The implications on a national level are that the Lebanese population and other neighboring Middle Eastern countries may require a more vigilant approach towards HPV detection and awareness, starting from the earliest stages of possible exposure. On an international level, our findings indicate that further research is required to better elucidate non-classical mechanisms of HPV exposure and transmission, and that HPV-positivity in OPSCC may play an important role regardless of geographic location.


Data regarding human papillomavirus (HPV) prevalence and genotype distribution are limited in Shandong Province, China. Therefore, we investigated the recent HPV prevalence and genotype distribution among females in Shandong and aimed to provide comprehensive data to guide HPV-based cervical cancer screening and HPV vaccination for this population of Chinese women.HPV testing results of 94,489 females were retrospectively reviewed and extracted from the database of Jinan KingMed Diagnostics, the largest independent pathology laboratory in Shandong Province, China. HPV was detected by a HPV genotyping panel from January 2011 to June 2017. The overall prevalence, age-specific prevalence, and genotype distribution were analyzed.A total of 26,839 cases (28.4%) were HPV-positive, with 4.3% positive for low- or undetermined-risk HPV (lr-/urHPV)-only, 18.1% positive for high-risk HPV (hrHPV)-only, and 6.1% positive for mixed lr-/urHPV and hrHPV infections. Single HPV infections accounted for 62.8%, while the rest were multiple HPV infections of two or more genotypes. HPV16 (5.8%), HPV52 (5.1%), HPV58 (3.5%), HPV51 (2.6%), and HPV56 (2.3%) were the five most common hrHPV genotypes; while HPV81 (2.8%), HPV53 (2.8%), and HPV6 (2.3%) were the three most common lr-/urHPV genotypes. HPV18 (1.7%) was only the ninth most common hrHPV genotype. HPV16 but not HPV52 was more common in single infections than in multiple infections. The distribution of both mixed lr-/urHPV and hrHPV as well as overall HPV infections demonstrated a bimodal pattern across age groups, of which the first peak appeared in the younger group and the second peak was found in older women. A similar age-specific distribution was observed in multiple infections of three or more subtypes as well. Moreover, the proportion of mixed lr-/urHPV and hrHPV infection significantly increased, while those of lr-/urHPV-only and hrHPV-only infections declined as the number of co-infections increased during the study period.This large daily clinical practice report shows that HPV prevalence and genotype distribution are different in this population, who had limited cervical cancer screening service, compared to those in developed countries. Therefore, different strategies should be developed for HPV-based cervical cancer screening and vaccine-based HPV prevention in Shandong Province. Globally, approximately 85% of the estimated 528,000 new cases and about 87% of 266,000 deaths from cervical cancer occurred in developing countries in 2012 [Human papillomavirus (HPV) infection has been confirmed as the main cause of invasive cervical cancer and its precancerous lesions , 9. MoreAt first, hrHPV detection was an alternative approach to the triage of equivocal abnormal cytology of cervical cancer screening , 13. CurThe HPV prevalence and genotype distribution differ between nations –23 as weJKD is the largest independent pathology laboratory in Shandong province, China. This study was approved by the institutional review committee of JKD. The review committee waived the need of patients’ consent due to anonymous analyses of the data. The management and publication of patient information in this study was strictly in accordance with the Declaration of Helsinki, including the confidentiality and anonymity. A retrospective database review was conducted to identify all cervical HPV genotyping results reported from January 2011 to June 2017. All the HPV tests were performed at the JKD Genetics Laboratory. The HPV genotyping results and relevant clinical information, including age and clinical history available in the pathology database, were all recorded. Cervical samples for HPV genotyping were collected from more than 500 hospitals, women’s health centers, community clinics, and physical examination centers. These institutes were primarily in suburban and rural areas across 17 cities in Shandong Province, one of the largest and most populous provinces in eastern China. More than 90% of the HPV tests were operated by clinicians during routine cervical screenings, while very few of them were ordered as a triage test after an equivocal abnormal cytology result.Exfoliated cervical cells at the orifice of the uterus and endocervical canal were collected using a specialized cervical brush. Then the cervical samples were stored at 4°C in the standard media provided with the panel  and shipped to the JKD Genetics Laboratory for HPV testing within 48 h. DNA isolation and purification were conducted according to the manufacturer’s instructions .All HPV tests were performed with a HPV genotyping panel (polymerase chain reaction (PCR)-reverse dot blot hybridization method; Yaneng Bioscience, Shenzhen, China). This multiplex PCR technique can detect 14 hrHPV genotypes  and 9 lr-/urHPV genotypes . As reported previously –32, HPV P < 0.05 was considered to be statistically significant.Data were analyzed with SAS 9.4 . All subjects were divided into four age groups  to calculate the overall HPV genotype prevalence, or into seven age groups  for the other analyses. The age (women with unknown ages were excluded) and co-infection number trends of HPV infection were analyzed by the Cochran–Armitage trend test. From January 2011 to June 2017, a total of 94,640 samples were collected for HPV infection detection at the JKD Genetics Laboratory, but only 94,489 cases (99.8%) were suitable for final statistical analysis due to the presence of β-actin. The HPV test results demonstrated that 26,839 cases were HPV-positive, and the overall prevalence of detectable HPV infection was 28.4%, with 4.3% positive for lr-/urHPV-only, 18.1% positive for hrHPV-only, and 6.1% positive for mixed lr-/urHPV and hrHPV infections.Ztrend = -14.00, Ptrend < 0.001). The highest prevalence was found in the youngest age group (9.8%), and the infection rate declined gradually as the age increased . In contrast, the distribution of mixed lr-/urHPV and hrHPV infection showed a bimodal pattern in different age groups . The highest infection rate was found in women ≤20 years old (27.7%), which declined gradually and reached its lowest point in the group of 41–50 year olds (4.0%), before another increasing trend in the older age groups (5.6% for the group of 51–60 year olds and 5.9% for women >60 years old). A similar age-specific prevalence pattern was found in overall HPV infection , with the first peak in women ≤20 years old (56.0%), and the second peak in women in their fifties (25.9%). Besides, hrHPV-only infection was very common, with the infection rate exceeding 15% in all age groups .After dividing the subjects into seven age groups , the HPV infection prevalence in each subgroup was calculated. As shown in The prevalence of each HPV genotype is shown in For the lr-/urHPV genotypes, HPV81 (2.8%), HPV53 (2.8%), and HPV6 (2.3%) were the three most common types . ObviousPtrend < 0.001). Starting from 33.7% in the youngest group, the infection rate increased gradually and reached its peak in the 41–50 year olds, and then it remained at a relatively high level for women >50 years old. However, an inverse distribution was observed in triple , quadruple , and ≥ five  HPV genotype infections. The highest infection rate was found in women ≤20 years old , which declined gradually as the age increased, reached the lowest levels in the group of 41–50 year olds , and then rose again in women >50 years old. Besides, no obvious difference was observed in the distribution of double genotype infections, with proportions exceeding 20% in all age groups .The age-specific distribution of single and multiple (two or more) HPV infections is summarized in The genotype distribution for single and multiple HPV infections is presented in Ptrend < 0.001), hrHPV-only , and mixed lr-/urHPV and hrHPV infections  were observed in co-infections with different numbers. The proportion of lr-/urHPV-only and hrHPV-only infections had the highest level in single HPV infection , and it declined gradually as the number of co-infections increased. In contrast, the proportion of mixed lr-/urHPV and hrHPV infection was the lowest in double HPV genotype infections (45.0%), but it rose dramatically as the number of co-infections increased.As shown in This study provided an enormous amount of HPV genotyping data from a largely unscreened Chinese female cohort in Shandong Province, China. The results revealed that the overall HPV-positive rate was 28.4%, with 4.3% positive for lr-/urHPV-only, 18.1% positive for hrHPV-only, and 6.1% positive for mixed lr-/urHPV and hrHPV infections, which were consistent with the results from several large-scale investigations of HPV prevalence and genotype distribution among other Chinese populations , 33, 34.Previous studies have demonstrated that HPV prevalence varies considerably in women from different regions and nations , 33, 34.The age-stratified analyses indicated a bimodal pattern of hrHPV prevalence among different age groups. The first peak was in the younger age group, while the second peak was in older women from China , 33, 34 in vitro diagnostic tool approved by the Chinese Food and Drug Administration in 2008 , was employed. Our recent study [It is necessary to know the HPV genotype distribution to select the spectrum of HPV genotypes for both HPV-based screening and vaccine development. In this study, the HPV genotyping panel of Yaneng Bioscience, a clinical nt study  showed tet al. [The HPV genotype distribution varies geographically in the general population, in cervical cancer patients, as well as in patients with precancerous lesions. Our study found that HPV16 (5.8%), HPV52 (5.1%), HPV58 (3.5%), HPV51 (2.6%), and HPV56 (2.3%) were the five dominant hrHPV genotypes in the population. This genotype distribution pattern is similar to previously reported data from several other Chinese population-specific investigations –29, 33. et al. [Apart from HPV16, HPV18 is known as the second most common oncogenic genotype in the general female population , 22 and et al.  have repFurthermore, this study showed that the three most common lr-/urHPV genotypes were HPV81 (2.8%), HPV53 (2.8%), and HPV6 (2.3%), inconsistent with previous results showing that HPV6 was the most frequently detected lr-/urHPV genotype among Americans (2.9%), followed by HPV11 and 61 . Both CeInvestigation of the prevalence of multiple HPV infection is also of great significance to understand its carcinogenic role in cervical cancer. Although women co-infected with HPV16 and other hrHPV genotypes have no higher risk for cervical cancer than those infected with HPV16 alone , severalAlthough this study provided large-scale information on the recent HPV prevalence and genotype distribution in Shandong Province, China, several limitations existed. First, most cervical screening tests received by JKD were either for HPV testing alone or cytology alone, while HPV and cytology co-testing were rare. Cervical cytology or histology results were not available for women included in the study; therefore, we were unable to correlate HPV infection and genotype distribution to different cervical abnormalities. It still remains as a clinical dilemma to manage appropriately such a large cohort of HPV-positive women without cytological evidence of cervical cancer or precancerous lesions. Second, detailed information on geographic, cultural, economic, and other backgrounds of this population was diverse; however, it was not documented in this study. Therefore, we were unable to specify the effect of these different backgrounds on the prevalence of HPV infection. Third, very few cases had HPV testing due to an equivocal abnormal cytology result. This might lead to overestimation of the actual prevalence of HPV infection, which also has been shown in several other Chinese studies , 33, 34.To the best of our knowledge, this study was the most comprehensive routine clinical assessment to reveal the prevalence of HPV infection and genotype distribution in a female cohort in Shandong Province, China. This study confirmed a high HPV prevalence and indicated a high cervical cancer incidence in this region, where well-organized screening has not been well established and prophylactic vaccines against HPV have not been available. The results showed that HPV16, 52, and 58 were the three most common hrHPV genotypes. These findings were consistent with those among other Chinese populations. However, the HPV genotype distribution pattern was clearly distinct from those found in developed countries. Further trials are needed to determine whether a different triage strategy should be developed when hrHPV testing is adopted as the primary screening modality in China. Meanwhile, the genotypic spectrum of the next-generation HPV vaccine for Chinese women should include other predominant hrHPV genotypes, such as HPV52 and 58.


The aim of this study was to introduce the VaccinaTion & Hpv Knowledge (THinK) questionnaire to assess knowledge about human papillomavirus (HPV) and attitude to HPV-vaccination. Its reliability and validity was demonstrated in a sample of women living in Sicily .A cross-sectional survey was conducted on a sample of 220 women at the “Paolo Giaccone” University Hospital in Palermo (Sicily), aged 18–61. Data were analyzed through Cronbach’s alpha and exploratory factor analysis, followed by a structural equation model with measurement component. The two-level data structure was explicitly considered.Three dimensions were found: “knowledge of HPV infection (kHPV), “Attitude to be vaccinated against HPV (aHPV)” and “Knowledge about vaccines (KV)” . Internal consistency was good for the whole questionnaire (0.82) and the first dimension (0.88) and acceptable for the second (0.78) and the third dimension (0.73). 23% of women showed no or little knowledge of HPV and 44.3% of women had no or little knowledge about HPV induced lesions.The use of a validated questionnaire may serve as a useful measure to assess general knowledge about HPV and attitude towards vaccination against HPV in the primary prevention setting. Human Papilloma Virus (HPV) infection is the most frequent among sexually transmitted diseases in the world. Cervical cancer is closely related to virus action, which is the main cause of cervical intraepithelial neoplasia and invasive lesions .Three HPV vaccines are at the moment available in many countries throughout the world. The bivalent  HPV vaccine prevents infections with the high-risk (HR) HPV 16 and 18. These genotypes are responsible for approximately 70% of cervical cancer cases globally and are considered responsible for a significant number of cervical low- and high- grade squamous intraepithelial lesions  . The quaA cross-sectional study showed a prevalence of HR HPV infections of 24% in a group of young Sicilian women (18–24) . AccordiAwareness of the risks associated to HPV infection is extremely important. In a large systematic review, The aim of this study was to assess knowledge of HPV and attitude to HPV-vaccination in a sample of Sicilian adult women and to demonstrate reliability and validity of the questionnaire used. The choice of an adult target population for this study relates to the importance of disseminating the culture of vaccination, just increasing parental awareness and attitude. The VaccinaTion & Hpv Knowledge (THinK) questionnaire was developed to be used in the first approach to the patient both in hospital and in outpatient service.A cross-sectional survey was conducted at the “Paolo Giaccone” University Hospital in Palermo (Sicily) from April to December 2017. The study included 220 women, aged 18-61, consecutively enrolled from the Unit of Gynecology and Obstetrics (Ob/Gyn) (136 women) and from the University ambulatory clinic (UAC) (84 women). The Ob/Gyn is an outpatient service for women of all age groups while the UAC supplies free healthcare services to students and fresh graduates. Women apply to the Ob/Gyn either as they complain about some acute or chronic disorders or as they ask for a complete gynecological check-up. Alternatively, women apply to the UAC in order to receive information on contraception, sexually transmitted diseases (STD) and/or gynecological screening visits. Women already vaccinated against HPV were excluded from the study.Enrolled women were given advices about the aim of the study. This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures were approved by the Research Ethics Committee at “Paolo Giaccone” University Hospital (Reference number 8/09/2018). Verbal informed consent was obtained from all participants. The THinK questionnaire included 16 items , using aDescriptive statistics were calculated for participants’ general characteristics.As a first step, an exploratory factor analysis (EFA) was carried out to describe the joint variability of the dimensions of the THinK questionnaire. Factors were rotated using the varimax approach to ease interpretation. Internal consistency was assessed for each dimension using the Cronbach’s alpha coefficient. Higher values indicate that scores on the considered dimension are internally consistent. Internal consistency is considered poor if the alpha value is below 0.60, questionable if between 0.60 and 0.70, acceptable between 0.70 and 0.80, good between 0.80 and 0.90 and excellent if not less than 0.90 . The samp-value <0.05 was chosen for statistical significance. Statistical analysis was conducted using Stata SE/14.2.As a second step, a structural equation model with measurement component was estimated to confirm the factor structure obtained through EFA. It was assumed a generalized linear model for ordinal response and link logit. As a final step, in order to take into account that participants are nested within two groups Ob/Gyn and UAC, a two-levels measurement model was considered. The LR test, AIC and BIC were used for comparison between the one-level and two-levels SEM models. The Student’s t-test was used to assess statistical significance of the difference between two women’s groups with respect to questionnaire’s items and dimensions. A All five experts concurred that the measures should effectively capture any changes in the knowledge about HPV and attitude to vaccination and HPV vaccines, with concern to the first approach to the patient both in hospital and in outpatient service.Women enrolled at UAC were on average younger (23.1 ± 2.45) and more educated (100% high school and more) than women enrolled at Ob/Gyn (35.5 ± 9.89 years old and 63% high school and more) .Three dimensions were found trough EFA: “knowledge of HPV infection (kHPV)” (48% explained variance), correlated with items between Q9 and Q13, “Attitude to get vaccinated against HPV (aHPV)” (26%), correlated with items Q14-Q15-Q16, and “Knowledge about vaccines (KV)” (23%), correlated with items from Q1 to Q5. Three items  resulted with high uniqueness (≥0.80). Internal consistency was good for the whole questionnaire (0.82) and the first dimension (0.88) and acceptable for the second (0.78) and the third dimension (0.73) .p = 0.0223).Results of the 1-level measurement SEM model confirmed the three factors structure of the THinK questionnaire . By inclNotably, 23.1% of responders showed poor knowledge of HPV and 16.7% had never heard of it (Q12); For what concerns specific immunization, 21.8% of patients (Q14) responded that they are very little or not at all available to carry out vaccination. Poor knowledge of HPV induced lesions was expressed by almost half of the women interviewed (44.3% of women answered no or little at Q11), without any correlation with age or education. About the 19% of women expressed a clear refusal just to receive even simple information about HPV vaccination (Q16) (data not shown in tables).On average, women enrolled at the UAC reported scores significantly higher compared to women enrolled at Ob/Gyn for Q3 (2.49 ± 1.41 vs 1.95 ± 1.12), Q14 (2.60 ± 1.70 vs 2.14 ± 1.20), Q15 (2.96 ± 1.79 vs 2.44 ± 1.28) and aHPV (0.17 ± 1.27 vs -0.28 ± 0.93). Conversely, their score was significantly lower for Q6 (2.96 ± 1.41 vs 3.57 ± 1.14) and Q7 (3.15 ± 1.15 vs 3.68 ± 1.14) .The aim of our study was to perform a reliability and validity study of the proposed THinK questionnaire as well as to assess knowledge of HPV and attitude towards HPV-vaccination in a sample of women living in Palermo.The THinK questionnaire was found to measure three domains, which we named knowledge of HPV infection, attitude to be vaccinated against HPV and knowledge about vaccines, and it demonstrated adequate internal consistency as a whole and for each one of its three domains. We developed a short and succinct questionnaire with only 16 items in order to get it easier to be used in the first approach to the patient both in hospital and in outpatient service. There are many studies employing questionnaires about HPV issues, but just few use validated questionnaires, and their validity results are in line with those found for the THinK questionnaire. The HAVIQ questionnaire , which wThe context proposed in our analysis concerns adult females living in Palermo. Rationale for choosing this target was to have indications about women that are yet (or not yet) mothers of girls and boys in vaccination age. Parents’ attitude about immunization is extremely important to vaccination of younger girl ; disagreWhen analyzing results of our paper, it is necessary to keep in mind that two groups involved in the survey are representative of two different populations. In fact, participants from Ob/Gyn are adult women referred for therapeutic purposes while those from the UAC are students or fresh graduates mostly referred for prevention and contraceptive prescription. Results from the 2-levels measurement SEM model showed that the group information explains a significant share of the total variability of the responses. This finding strengthens the importance of validating the questionnaire to measure HPV knowledge in specific populations.One important finding of our study is that more than one in three of women were not conscious about HPV prevention and one in five would be only a little or not willing to be vaccinated against HPV. The roots of these disappointing results can be explained by a general poor knowledge of HPV , lack ofOur results are consistent with Censis data, which show that judgment on available information on HPV and vaccinations is not positive, in terms of clarity and quantity .By evaluating answers to the last question, it is possible to hypothesize a strong cultural resistance to vaccination and let us to reflect that a rooted resistance to immunization could play an important role in the HPV vaccine hesitancy . CompariDifferent authors showed the impact of socioeconomic variables on HPV awareness and vaccination: a few reported positive relationship between school education and mother’s school level, HPV knowledge and vaccination , betweenThrough this study, we have provided initial evidence for validation of the THinK questionnaire. There are some margins for improvement of the instrument, as deleting those items resulted with high uniqueness or including additional items to get it more HPV-specific, e.g., concerning sexual behaviors , knowledge about HPV induced lesions, smoking cigarettes, alcohol consumption, use of hormonal contraceptives or IUD, personal hygiene, prior infections of the cervico-vaginal tract, parity, HSV. Finally, more research is desirable to examine other aspects as concurrent validity and test-retest reliability with larger sample sizes.The THinK questionnaire demonstrated adequate reliability and validity in a sample of Italian women living in Palermo. This instrument, short and easy to complete and to score, may serve as a useful measure in the primary healthcare setting in order to assess general knowledge about vaccination and HPV vaccines. Even if, in agreement with the guidelines of the Italian Ministry of Health, HPV vaccination is offered free of charge to girls in the twelfth year of life in all Italian regions since 2007/2008, efforts must be made to create a sound basis for understanding HPV issues and related risks, with a view to preventing and protecting patients.10.7717/peerj.6254/supp-1Data S1Click here for additional data file.


Cervical Cancer is still a major public health challenge in low and middle-income countries. HPV testing has been an innovative approach, which was introduced in Argentina for women aged 30+ through the Jujuy Demonstration Project (JDP) carried out between 2012 and 2014. After a positive HPV-test, cytology is used as triage method. Under this protocol, the group of women with HPV+ and normal cytology are recommended to repeat the test within 12–18 months. Studies have shown that this group has increased risk of CIN2+, however, assuring high levels of repeating test among these women is difficult to achieve. We analyze those factors associated with lower re-test attendance among HPV+/ cytology negative women at a programmatic level in low-middle income settings.n = 49,565). We performed a set of different adjusted logistic regression models.We used data of women aged 30+ HPV-tested in the JDP and followed until 2018  tests/self-collected (SC) tests), and span between HPV-test collection and report of results.p < 0.001), aged 64+  were less likely to be retested; while women with clinician-collected samples had higher odds of being re-tested .Forty nine thousand five hundred sixty five women were HPV-tested and 6742 had a positive HPV-test. Among HPV+ women, a total of 4522 were HPV+/Cytology negative (67.1%). In total, 3172 HPV+/Cytology negative women (70.1%) had a record of a second HPV test as of March 2018. Only 1196 women (26%) completed the second test within the timeframe. Women with no record of a previous Pap (OR: 0.46, 95% CI: 0.4–0.53, Low re-test rates were found in HPV +/ normal cytology women. Tailored interventions are needed to increase the effectiveness of the screening in this group, especially for those women with characteristics associated to lower attendance. Cervical cancer is still a major public health challenge in low and middle-income countries. Unsuccessful screening strategies have been pointed out as one of the major barriers to reduce the morbidity and mortality . CytologNonetheless, screening strategies based on HPV testing as primary screening have opened new challenges; one is the fact that HPV-testing identifies women positive for HPV but does not inform which of these women have pre-neoplastic disease. In order to identify those women with lesions that need to be referred for further diagnosis, triage methods are used. Many countries use cytology for triage, including Argentina, and it is one of the recommended methods indicated by WHO guidelines . CytologAssuring high levels of re-test among these women is particularly important, as studies have shown that they are at increased risk of CIN2+, even when the repeat HPV test is negative , 9. Re-tHowever, despite the importance of following-up this group, evidence indicates that assuring high levels of re-test among these women is difficult to achieve , especiaEvidence from cytology-based programs has shown that in general, completion of follow-up steps and adherence to recommended timeframes is especially difficult to achieve for women with low socio-economic level, as well as for those who face geographic, and health system barriers to health care –16. ThesAs today, there is no study assessing factors that might be associated with lower rate of re-test among HPV+/ cytology negative women in programmatic context in low-middle income populations. In Argentina HPV-testing was first introduced through the Jujuy Demonstration Project (JDP), during 2012–2014 [We analyzed data collected for the JDP, carried out between 2012 and 2014 , but sucData of the JDP was registered in the National Screening Information System,  implemented by the National Cervical Cancer Prevention Program (NCCPP). SITAM is a unified database that collects data about screening, diagnosis and treatment of all women attending the public health system. Those that were initially screened by the public sector but continued their follow-up in private services were recorded in SITAM only upon confirmation by the provincial prevention program; otherwise they were considered as loss to follow-up. For this analysis, we included women aged 30 years and older HPV-tested between 2012 and 2014 for the first screening test and data until 2018 for their re-test. We do not consider second tests that were done after a five-year period. Detailed description of how data is collected by the NCCPP is described elsewhere . The datIndependent variables considered for this study were age, health insurance status, year of HPV-testing, record of previous Pap, HPV-testing modality (clinician-collected (CC) tests/self-collected (SC) tests), and span between HPV-test collection and report of results. This last variable is included as a proxy measuring the laboratories’ time efficiency processing the samples.Primary outcomes were re-test attendance, and re-test attendance within recommended timeframe, both recorded as dichotomous variables. Re-test was considered within the recommended time frame when was performed between month 12 and 18 after primary screening . Women wWe performed a set of descriptive statistics and different logistic regression models.p-values.First, a multivariable regression was used to examine the association with re-test attendance of the following variables: age, health insurance status, year of HPV-testing, record of a previous Pap test, HPV-testing modality, and span in days between HPV-test collection and when result report was available in the system. We report odds ratios with 95% confidence intervals and Secondly, we analyzed factors associated with re-test attendance within the recommended timeframe as outcome. Last, we performed a logistic regression including only women with re-screening test to assess the association of the covariates and the outcome within this group. This model worked as a sensitivity analysis model that helped to evaluate the association of the covariates and the outcome in this subset of women.In order to explore possible interactions between the covariates, we tested different regressions including interaction terms for each pair of variables. Furthermore, we ran a model stratifying the data by year to confirm the associations for each year data. R Statistical software and R-Studio were used to perform the analysis.For the period 2012–2014, 49,565 women were tested using HPV-test as primary screening test. Socio-demographic characteristics of these women are presented in Table p < 0.001). Moreover, those women aged 64+ were also less likely to be re-screened, having 0.46 times the odds of being re-screened when compared to those aged 30–34 . Women with CC tests had 1.42 times the odds of being rescreened compared to those with SC HPV-tests . Women HPV-tested during 2013 and 2014 were less likely to be re-screened . Stratifying by year, results are consistent, being age, record of a previous Pap test, and HPV-test collection modality significant predictors. No significant interaction was found in the model testing all the covariates pairs.Results of the multivariate regression are shown in Table p < 0.001), while women with no record of a previous Pap test were less likely to be-rescreened within 12–18 months .When the outcome considered for the model was re-screening within the recommended time frame, being CC HPV-tested increased 2.10 times the odds of re-screening within 12–18 months . On the contrary, women who had CC HPV-testing were more likely to be re-screened within the recommended timeframe. . The other covariates showed no statistically significant results.Among the subset of re-screened women, the odds of re-screening within the recommended timeframe were reduced for those without record of a previous Pap test  and Li (2017) found that women in this age group have a higher rate of HPV persistent infection and a higher incidence of cervical cancer , 34. FurOur study also found significant reduced odds of attending to rescreening among those women with no previous record of a Pap. In line with what other authors discussed, this factor seems to be linked to persistent socio-economic and geographic barriers to access health services, as well as the inadequacy of the health system to provide required services, indicating not only a barrier in the past, but a lasting obstacle to for appropriate follow-up , 31.Moreover, women with CC HPV-Tests were at increased odds of re-screening. Women offered SC tests in the JDP were socially vulnerable women, with reduced access to screening . ArrossiThere are different strategies described for decreasing the number of lost to follow-up in cervical cancer screening. Referral to colposcopy of these women implies a significant burden for the health system that will not be translated in better screening outcomes . SettingNotwithstanding the useful information provided by this study for future research on HPV+/Cytology negative women, and the contribution for further programmatic evaluations, a number of limitations exist. First, the population analyzed is that targeted and reached by the NCCPP, which might not be representative of the whole population. Also, the variables observed were those that the program collects as routine, other significant variables were not possible to include in the analysis. Further studies are needed to scale up these conclusions. Second, the nature of this study is observational, and it is not conclusive evidence of causal relationship between the variables analyzed and the outcome. Moreover, while in randomized study designs it is expected that unobserved confounders are randomly distributed among the groups without affecting the association between exposure and outcome, in this study -an observational study- unobserved confounder might be biasing the results.Furthermore, the lost to follow-up is also a limitation for this study, since women that opt to continue their follow-up using private health providers are not necessarily included in SITAM.The transition to HPV test-based screening programs has defined a new group of women, those with an HPV +/normal cytology result. Low re-testing and low adherence to protocol recommendations have been found in this population. Our study found three factors associated to low attendance to re-screening: women without record of a previous Pap test, being aged 64+ and being screened with SC-tests. Further studies are needed to properly assess the risk of this group of women, and specific interventions might be needed to increase the effectiveness of the screening programs among HPV+/Cytology negative women. Particularly, among the groups that this study found associated to higher lost to follow-up, setting tailored measures, such as the reduction of barriers in the access and the implementation of logistics changes on how to deliver the results should be considered for future interventions.