We find that the magnetic properties of such substitutional impurities can be understood in terms of a simple model based on the Hund’s rule. The TM-doped black phosphorenes with Ti, V, Cr, Mn, Fe, and Ni impurities show dilute magnetic semiconductor (DMS) properties while those with Sc and Co impurities show nonmagnetic properties. On the other hand, the TM-doped blue phosphorenes with V, Cr, Mn, and Fe impurities show DMS properties, with Ni impurity showing half-metal properties, whereas Sc- and Co-doped systems show nonmagnetic properties. We identify two different regimes depending on the occupation of the hybridized electronic states of TM and phosphorous atoms: (i) bonding states are completely empty or filled for Sc- and Co-doped black and blue phosphorenes, leading to nonmagnetic; (ii) non-bonding d states are partially occupied for Ti-, V-, Cr-, Mn-, Fe- and Ni-doped black and blue phosphorenes, giving rise to large and localized spin moments. These results provide a new route for the potential applications of dilute magnetic semiconductor and half-metal in spintronic devices by employing black and blue phosphorenes.We present first-principles density-functional calculations for the structural, electronic, and magnetic properties of substitutional 3PACS numbers: 73.22.-f, 75.50.Pp, 75.75. + a As the allotrope of black phosphorene, blue phosphorene has the same stability as black phosphorene at room temperature, and its band gap is larger than black phosphorene [Two-dimensional 2D) materials, graphene and silicene, are currently the subject of intense theoretical and experimental research especially for their novel electronic device applications , 2. GrapD materiasphorene . These gsphorene –23.For the design of practical electronic devices, defects and impurities have been employed to tune the electrical, optical, and other properties. Over the last decades, the resulting dilute magnetic semiconductors (DMS) and half-metals have achieved important developments both in fundamental aspects and prospective technological applications , 25. IndMeanwhile, in spite of the success of 2D materials such as graphene, silicene, transition metal dichalcogenides (TMDCs) , and blad TM impurities (from Sc to Ni) in black and blue phosphorenes to investigate their dilute magnetic characters and half-metal properties. Using first-principles density functional theory (DFT) calculations, we study the structural, electronic, and magnetic properties of substitutional 3d TM impurities in black and blue phosphorenes. One of our key results is that the electronic and magnetic properties of these substitutional impurities can be understood by a simple model based on the hybridization between the TM d orbitals and the defect  levels. This model together with the calculated band structure provides an explanation for the non-trivial behaviors of the binding energy and the spin moments for all the systems considered. Concisely, we distinguish two different regimes that depend on the electron filling of TM-phosphorous hybridized levels: (i) completely unoccupied (occupied) bonding states for Sc (Co) lead to nonmagnetic and (ii) partially occupied non-bonding d shell for Ti, V, Cr, Mn, Fe, and Ni give rise to large and localized spin moments.In this work, we focus on substitutional 3This paper is organized as follows. After a brief description of the computational details, we present the geometry structures, binding energies, and magnetic properties of all the substitutional TM impurities studied. We also present the general ideas behind our model of the metal-phosphorus hybridization in the considered systems. Then, the electronic structure of the unreconstructed Cd TM impurity atoms, we also considered the effect of the on-site Coulomb interaction U on the magnetic property within the PBE + U method. The values of U are 4.0, 5.5, 3.3, 3.5, 4.3, 3.3, and 6.5 eV for Sc-, Ti-, V-, Cr-, Mn-, Fe-, Co-, and Ni-doped systems, respectively. The kinetic energy cutoff of the plane-wave basis set used was 500 eV, and for the structural optimization, convergence of Hellmann-Feynman residual forces less than 0.01 eV/Å per atom was achieved. Because the convergence with respect to the number of k-points was especially critical to obtain accurate results for the spin moment in the systems studied, we used an adequate number of k-points for all the different supercell sizes, equivalent to 9 × 9 × 1 Monkhorst-Pack [1The present DFT calculations were performed using the Vienna Ab initio Simulation Package (VASP) code with a plane-wave basis set . Projectrst-Pack  samplinga1=3.310 Å, a2=4.589 Å, and θ′=60°, which are in good agreement with previous DFT calculations [The typical structure of the systems studied in this paper is presented in Fig. 11ulations . Figure ulations .μB/unit cell, most of which is concentrated at the two P atoms with the unsaturated bonds, as seen in Fig. 1We begin to study pure black and blue phosphorenes with a monovacancy. Because the blue phosphorene with monovacancy has no magnetism, we only plot the spin charge density of the black phosphorene with monovacancy in Fig. 11θ1 and θ2 monotonically increase from Sc to Ni  of the TM-doped black phosphorenes, where Eb is defined as –. Here, Etotal is the energy of the whole configuration, Ephosphorene is the energy of the phosphorene with a vacancy, and Eatom represents the energy of an isolated dopant atom. We find a continuous increase of the binding energy from Sc to Cr, and then decrease from Mn to Ni, and the binding energies for the considered TMs are in the range of 0.375–5.466 eV. Interestingly, Cr-doped system has the maximum binding energy. This peculiar behavior is related with the interplay between the energy down-shift and the compression of the 3d shell of the TM as the atomic number increases. Although this explanation will be more clear when the metal-phosphorus hybridization levels are discussed below, we note that the behavior of the binding energies of the substitutional 3d TM arises from two competing effects: (i)d1 and d2 reflects an increase in the bonding strength between the TM and phosphorous atomsFrom Sc to Cr, the decrease of (ii)d shell is occupied, its hybridization with the phosphorous vacancy states is weakened to decrease the binding energyFrom Mn to Ni, as the 3Figure 2It is noticeable that this trend of the energetics for the TM-doped black phosphorenes is very similar to that for the TM-doped blue phosphorenes see Fig. f.μB from Sc to Ni, respectively. On the other hand, the TM-substituted black phosphorenes have the zero magnetic moment for Sc and Co, but 1, 2, 3, 2, 1, and 1 μB for Ti, V, Cr, Mn, Fe, and Ni, respectively, which are the same as the corresponding cases in blue phosphorene. For both of the TM-substituted black and blue phosphorenes, we analyze the charge transfer using Bader charge  in graphene is smaller by 1 μB compared to the corresponding one in black and blue phosphorenes. This may be attributed to the different bonding natures of graphene and phosphorene: i.e., sp2 bonding in graphene and sp3 bonding in phosphorene. Since one valence electron of TM impurities in graphene participates in π bonding with neighboring C atoms, the spin moment is likely to decrease by 1 μB. To understand this deeply, we draw the schematic diagram of spin moment according to Hund’s rule in Fig. 3d14s2, 3 d24s2, 3 d34s2, 3 d54s1, 3 d54s2, 3 d64s2, 3 d74s2, 3 d84s2, respectively. Briefly, we can distinguish the several regimes depending on the filling of electronic levels: ■■■(i) Sc-doped black phosphorene have the empty Sc-phosphorous bonding levels, leading to a zero spin moment.■■■(ii) Co-doped black phosphorene have fully occupied Co-phosphorous bonding levels, leading to a zero spin moment.■■■μB, respectively.(iii) Ti-, V-, and Cr-doped black phosphorene have partially occupied TM-phosphorous bonding levels with the spin moments of 1.00, 2.00, and 3.00 ■■■d levels with the spin moments of 2.00, 1.00, and 1.00 μB.(iv) Mn-, Fe-, and Ni-doped black phosphorene have partially occupied non-bonding 3Interestingly, as shown in Fig. 3s and d in the outermost orbital of TM atoms and phosphorus atom are very close to each other.It is notable that the spin moments of TM-doped blue phosphorene see Fig. c are theSM) have a dominant contribution for the nearest phosphorus neighbors (SP1 and SP2). The calculated spin moments of TM impurities for Ti, V, Cr, Mn, Fe, and Ni in doped black phosphorene are SM=0.986,1.977,3.082,2.207,1.097, and 0.953 μB, respectively, close to the above-discussed Hund’s analysis. Similarly, the spin moments of TM impurities for Ti, V, Cr, Mn, Fe and Ni in doped blue phosphorenes are SM=0.992,2.032,3.147,1.954,1.247 and, 0.967 μB, respectively.To explore the underlying mechanism of the magnetic moments in TM-doped black and blue phosphorenes, the Mulliken population analysis was performed to list the results in Table μB, indicating a dilute magnetic property.Before the analysis of the electronic structures of TM-doped black and blue phosphorene, we first examine the electronic structure of a single phosphorous vacancy in black phosphorene. As substitutional impurities in black phosphorene, most of the TM atoms studied here exhibit a symmetrical configuration of Cment}2h3 . For thiTo further shed light on the underlying mechanism of magnetic properties in the TM-doped black and blue phosphorene structures, we plot the spin-polarized band structures of TM-doped black and blue phosphorenes in Fig. 555Generally, substitutional TM impurities in black and blue phosphorenes exhibit very similar behaviors in their energetic and magnetic properties. This result indicates that the structural differences of black- and blue-phosphorene lattices are insensitive to determine the energetic and magnetic properties of TM-doped black and blue phosphorenes, as shown in Figs. U on the magnetic properties of the substitutional 3d TM impurities in black and blue phosphorenes. We perform the PBE + U calculations for all the considered systems, where the values of U = 4.0, 5.5, 3.3, 3.5, 3.5, 4.3, 3.3, and 6.5 eV are chosen for Sc-, Ti-, V-, Cr-, Mn-, Fe-, Co-, and Ni-doped systems, respectively [U band gaps (Eg) of Sc-, Ti-, V-, Cr-, Mn-, Fe-, Co-, and Ni-doped black and blue phosphorenes are listed in Table Eg of the magnetic semiconductor obtained using PBE + U increases by ∼30 % compared to the PBE results. However, it is noticeable that the spin moment does not change depending on the PBE and PBE + U methods. Interestingly, we find that the PBE + U band structure of Ti-doped blue phosphorene shows a magnetic semiconductor property with a gap opening (see Fig. U in Ti-doped blue phosphorene splits the narrow half-filled bands crossing the Fermi level into lower and upper Hubbard bands. On the other hand, the half-metallic character of Ni-doped blue phosphorene predicted by PBE is preserved in the PBE + U band structure (see Fig. 5It is interesting to examine the effect of the on-site Coulomb interaction ectively –40. The EF and show a gap opening, indicating dilute magnetic semiconducting properties. We note that the DOS of Sc- and Co-doped blue phosphorene show nonmagnetic properties; those of Ti- and Ni-doped blue phosphorene show half-metal properties; V-, Cr-, Mn-, and Fe-doped blue phosphorenes show dilute magnetic semiconductor characters (see Fig. 7dxy and A general picture of the dilute magnetic and half-metal features of the TM-doped black and blue phosphorenes can be seen from the analysis of the spin-polarized total and partial DOS, as shown in Fig. 7d TM impurities in black and blue phosphorenes. We provided a simple model based on Hund’s rule for understanding the calculated electronic and magnetic properties of the considered systems, where the dilute-semiconducting and half-metal features, spin moment, and binding energy are varied depending on the atomic number of the TM atoms. The spin-polarized band structures and DOS calculations show that for black phosphorene, the Ti-, V-, Cr-, Mn-, Fe-, and Ni-doped systems have dilute magnetic semiconductor properties, while Sc- and Co-doped systems have no magnetism. For blue phosphorene, the Ni-doped system shows half-metal properties, while V-, Cr-, Mn-, and Fe-doped systems show dilute magnetic semiconductor characters, Sc- and Co-doped systems show non-magnetism.We have performed a first-principles DFT calculation for the structural, energetic, and magnetic properties of a series of substitutional 3d TM atoms in black and blue phosphorenes exhibit some intriguing electronic and magnetic properties, such doped systems can provide an interesting route to tune various functions for spin electronic devices based on black and blue phosphorenes. This functional ability together with the high stability of substitutional impurities can open a route to fabricate ordered arrays of these impurities at predefined locations, which would allow the experimental tests of the theoretical predictions of unusual magnetic interactions mediated by black and blue phosphorenes.Since substitutional impurities of 3


To estimate the prevalence of oral detectable human papillomavirus (HPV) DNA in HIV-negative men who have sex with men (MSM) attending a sexual health clinic in London and concordance with anogenital HPV infection. Such data are important to improve our understanding of the epidemiology of oral HPV and the potential use of vaccines to prevent oropharyngeal cancers.Paired oral rinse samples and anogenital samples were available from 151 HIV-negative MSM within a larger cross-sectional survey. All samples were tested in parallel for 21 types of HPV DNA using an in-house assay.The median age of participants was 30 (IQR 25–35). The prevalence of any oral HPV and of high-risk HPV (HR-HPV) was 13.7%  and 5.9%  compared with 64.9%  and 34.4%  in any anogenital sample, respectively. The prevalence of types prevented by the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccines was 1.3% (95% CI 0.2 to 4.7), 2.6% (95% CI 0.7 to 6.6) and 4.6% (95% CI 1.9 to 9.3), respectively. There was no concordance between HPV genotypes detected in oral and anogenital sites.HR-HPV DNA, including HPV 16/18, was detected in oral specimens from HIV-negative MSM attending sexual health clinics, suggesting a potential role for vaccination, but is far less common than anogenital infection. How this relates to the risk and natural history of HPV-related head and neck cancers warrants further study. Lack of concordance with anogenital infection also suggests that oral HPV infection should be considered separately when estimating potential vaccine impact. Human papillomavirus (HPV) infection is associated with cancers at a number of sites in the head and neck, most importantly oropharyngeal cancer, which has been rising in incidence in recent decades.6Estimating the potential benefit of vaccinating MSM requires knowledge of the epidemiology of oral HPV infection. To date, only three studies involving a total of 877 HIV-negative MSM have been conducted to estimate oral high-risk HPV (HR-HPV) prevalence, and results are not consistent 2%, 17%8. LiMost transmission models of HPV infection used to inform vaccine programme design assume that infection occurs through anogenital contact, ignoring the role of oral–anogenital contact. Indeed, estimates of concordance between oral and anogenital HPV infection not only have implications for vaccine assessment but also for understanding the key epidemic characteristics such as route of acquisition, whether anogenital infections are acquired simultaneously or via separate risk acts/partnerships, or whether men transfer infections from one anatomical site to another (auto-inoculation).We describe age-specific oral HPV prevalence and the concordance between detection of type-specific HPV DNA in oral and anogenital specimens from HIV-negative MSM attending a sexual health clinic in central London.Study methods, including sample size calculations, have been reported elsewhere.Participants who enrolled in the final five months of the study were also invited to provide an oral specimen involving a 30 s gargle/rinse with 15 mL of Scope mouthwash according to a published protocol.Here we report HPV prevalence and demographic and behavioural characteristics among participating MSM with both oral and anogenital specimens that were adequate for PCR-based HPV detection, for bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccine-preventable types together and individually, and for selected other HPV types: 35/39/51/56/59/68/26/53/66/70/73/82. CIs (95%) around prevalence estimates were determined by the Clopper–Pearson (exact) method.There were 522 participants in the full study (n=522) and 177 gave an oral specimen. Participant and specimen numbers are shown in online supplementary figure S1. The study population was slightly younger than MSM attending MMC during the recruitment period (data not shown) and were more likely to be a new patient at the clinic than those who declined to participate; 163/173 (94%) HIV-negative MSM provided oral specimens, 153/173 (88%) were adequate for HPV testing and 151/173 (87%) had at least one matching anogenital specimen . Also, 127/151 (84%) had an anal swab, 135/151 (89%) had an external genital swab and 143 (95%) had a urine specimen.Online supplementary table S1 displays characteristics of substudy participants. The median age of respondents with adequate paired specimens was 30 (IQR 25–35), 75% were of white ethnicity and 64% had >30 lifetime sexual partners.Nine MSM had HR-HPV DNA detected in their oral specimens, and three had LR-HPV. Our observed prevalence of oral HR-HPV of 6% was higher than that of the global estimate in healthy men and women  yet the CIs overlap.w1Differences in estimates of oral prevalence between studies could be due to both technical and population differences. Methods of oral specimen collection, processing, storage, DNA extraction and test sensitivity and specificity differ across studies. We followed the oral rinse collection protocol from the Human Papillomavirus Infection in Men (HIM) study that is thought to yield more HPV DNA from the entire oral cavity than oral swabs and used a similar processing method.w2 In a cross-sectional assessment, persistent infections cannot be differentiated from those that are transient, and we did not measure oral cavity symptoms, but our lower oral prevalence as compared to anogenital prevalence may be due to both a lower incidence at oral sites and a lower proportion of persistent infections. While we have grouped HR-HPV types, defined by their oncogenic potential at the cervix, there is only evidence for HPV16 being associated with head-and-neck cancers.w3In the longitudinal Multicenter AIDS Cohort (MAC) study, HPV, particularly HR-HPV, in MSM was more likely to persist at the anus than the oral cavity, while heterosexual men were as likely to have persistent oral HPV as MSM, but less likely to have persistent anal HPV.et al (predominantly MSM)w4 and Parisi et al.w5 However, Edelstein et al found that 15/17 men  had the same type detected at oral and anogenital sites.w6 Lower prevalence in the oral cavity and the lack of concordance with anogenital infection suggest that oral HPV infections are acquired independently of anogenital infections, or that they are less likely to reactivate from latency than anogenital infections, and would also suggest that auto-inoculation does not commonly occur. Differences in sensitivity of the detection methods may also have contributed to some disparity in HPV detection between anatomical sites but is unlikely to account for the magnitude of the difference observed.Our finding of a lack of concordance between oral and anogenital specimens is similar to those in HIV-positive men reported by Videla We have previously demonstrated that our study population is at greater risk of STI acquisition than MSM attending other SHCs in England and MSM who attend SHCs in the general population of Britain.The sample size of this substudy was too small to accurately estimate oral–anogenital concordance  but could estimate oral prevalence within 5% if the true population prevalence was 13%.w7 but whether they are effective against HPV-related head and neck cancers has yet to be shown. The lack of concordance between oral and anogenital specimens suggests that the additional potential benefit of HPV vaccination for preventing oral HPV-related disease should be considered in epidemiological and natural history models, in addition to anogenital HPV infection. Further studies, including meta-analyses, are needed to elucidate the epidemiology and natural history of oral HPV infection.HPV vaccines can prevent oral HPV infections,


P = 0.039). Moreover, 37% of women showed cervical SIL: 14 ASC-US, 15 LSILs, 4 HSILs, and 1 in situ cancer. The presence of both LR and HR-HPV in women was independently associated with SIL (P = 0.003 and P = 0.0001). HR-HPV and atypical cytology were frequently identified in our cohort. HPV screening should be mandatory in HIV-infected subjects, and vaccine programs for HPV-negative patients should be implemented.The aim of this study was to assess the prevalence of HPV infection and determinants of abnormal cytology in HIV-positive patients. In a cross-sectional study, patients of both sexes, asymptomatic for HPV, underwent anorectal (men)/cervical (women) and oral swabs. Cytology and HPV-PCR detection/genotyping  were performed. A total of 20% of the 277 enrolled patients showed oral HPV, with no atypical cytology; in men, anal HPV prevalence was 81% with 64% HR genotypes. In women, cervical HPV prevalence was 58% with 37% HR-HPV. The most frequent genotypes were HPV-16 and HPV-18; 37% of men and 20% of women harbored multiple genotypes. Also, 47% of men showed anal squamous intraepithelial lesions (SILs); 6% had high- and 35% low-grade SILs (HSILs/LSILs); 5% had atypical squamous cells of undetermined significance (ASC-US). HR-HPV was independently associated with anal-SIL in men ( Human papillomavirus (HPV) is one of the most common sexually transmitted pathogens, responsible of several different diseases ranging from benign common warts to invasive carcinoma at a variety of anatomical sites, including the cervix, vulva, vagina, penis, anus, and oropharynx .While the immune system eliminates over time most HPV infections in immunocompetents individuals, HPV infections tend to persist in immunodeficient ones, such as HIV-positive subjects, probably due to the inability to control the expression and replication of HPV by HIV-compromised immune system . PersistMany studies have shown a higher incidence of HPV-related cervical cancer  in HIV-pThe effect of highly active antiretroviral therapy (HAART) on the incidence of HPV-associated infection and related neoplasia is controversial. Several studies have indicated that the incidence of anal cancer but not cervical cancer is increased with HAART , 8. At tEpidemiological studies on local  prevalence of HPV cervical infection in HIV-negative women published in recent years showed HPV prevalence ranging from 8.8%  to 38%  dependinGiven these considerations, the aims of our study were to assess the prevalence, genotype diversity, and determinants of HPV infection at different mucosal sites  in a cohort of HIV-positive men and women asymptomatic for HPV. Furthermore, we wanted to assess the prevalence of atypical cytology at different sites and to identify any demographic and clinical factors associated with the development of intraepithelial lesions, considered precancerous lesions. We performed a cross-sectional study in a cohort of HIV-positive men and women followed at the Clinic of Infectious Diseases, Department of Health Sciences, San Paolo Hospital, Milan, between January 2009 and February 2011. Inclusion criteria were HIV positive, age ≥18 years, routinely followed by the clinic, asymptomatic for genital diseases, and signed the informed consent to participate the study. Exclusion criteria were history of anal/cervical cancer, ongoing genital signs and symptoms , and refusal to sign the informed consent. http://dx.doi.org/10.1155/2013/915169).Patients were asked to complete an anonymous structured questionnaire on sexual behavior. The questionnaire was not validated; 14 self-reported questions were asked on the number of partners, genital intercourse, oral intercourse, and history of sexually transmitted diseases (STDs)  and anal specimens (men) were collected to analyze cytology and detect HPV. Oral specimens were obtained during the dentistry visit for both sexes for the same analyses. In particular, the oral sample was obtained by scraping the walls of the oropharyngeal cavity and gums using a dermatologic curette  with tangential movements at about 30 degrees on the mucosal. Then with the help of a Heidemann spatula, the material collected was smeared on a slide for citologyc analysis. Another sample obtained in the same way was collected in liquid-based cytology medium (PreservCyt-Hologic) for HPV detection and genotyping.Anal, cervical, and oral cytology samples were collected using a Dacron swab to perform a pap smear. The cytology was read by expert cytopathologists, with expertise in oral cytology and classified according to the 2001 Bethesda System terminology as negative, atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells that cannot exclude high-grade SILs (ASC-H), low-grade SILs (LSILs), high-grade SILs (HSILs), or carcinoma . Unsatishttp://blast.ncbi.nlm.nih.gov/) to identify the viral genotype. The oncogenic risk of the different viral genotypes was defined according to the epidemiologic classification by Muñoz et al. [Specimens from the cervical, oral, and anal mucosae were collected in liquid-based cytology medium (PreservCyt-Hologic). Total DNA was extracted using a commercial kit . HPV DNA was detected with PCR using both the L1 consensus primers MY09/MY11  and the z et al. .Demographic and immunovirological characteristics of the population were summarized using absolute numbers and percentages for categorical variables and medians and interquartile ranges (IQRs) for continuous variables. Categorical and continuous parameters were compared between HPV-negative and HPV-positive patients of the entire study population using Pearson's chi-square test and the Mann-Whitney test.Two univariate and multivariate logistic regression analyses were performed to explore factors associated with anal (model 1) and cervical (model 2) dysplasia in men and women, respectively. The following variables were included in the model: age, exposure categories for HIV infection , CDC stage C  [The analyses were performed using SPSS software (version 18.0).P = 0.0001), lower CD4 counts at Nadir , and a longer duration of HAART  compared with men. Demographic characteristic of the study population according to HPV infection status are shown in P = 0.01) and anal intercourse  more frequently than women; oral intercourse was reported by 87% of patients  were females. Female prevalence of the study population is consistent with the gender distribution in our clinic, with around 2/3 of patients that were males and 1/3 females, according to Italian data . Demograents see . A totalEach subject underwent a surgical (men) or gynecological (women) visit; 201 patients (72%) underwent also a dental visit (61 women and 140 men). The subjects were analyzed for both HPV infection and abnormal cytology at genital and oral sites. A total of 40 (20%) tested individuals harbored HPV infection at the oral site, and 18 (9.0%) had HR-HPV genotypes. The overall prevalence of anal HPV in men was 81% (145/180 men), and HR-HPV was detected in 114/145 of them (78.6%). Cervical HPV was detected in 56 (58%) of the 97 tested women, and 36/56 (64.3%) harbored HR-HPV. Globally, HPV was detected at genital sites  in 201 individuals (72.6% of the cohort), and 150/201 (74.6%) harbored HR types.A total of 78/201 subjects (38.8%) tested at both genital and oral sites showed concordant HPV serostatus (HPV positive in 32 cases and HPV negative in 46 cases); positivity at only the oral site was found in 7 cases (3.5%), and HPV was only detected at genital sites in 116 cases (57.7%). P = 0.0001) and more frequently infected through sexual routes . HPV-coinfected individuals were at a less advanced stage of HIV disease than HPV-negative ones, as documented by the shorter duration of HIV infection  and higher nadir CD4 cell counts . Current HIV RNA copy levels were higher in HPV-positive subjects . Atypical cytology was diagnosed in 18/76 (23.7%) HPV-negative and 99/201 (49.2%) HPV-positive subjects (P = 0.0001)  . Among males completing the questionnaire, having more than 25 sexual partners, anal and oral intercourses were more frequent in HPV-positive individuals than HPV-negative ones. Among women, those with HPV cervical infection had a higher occurrence of other STDs . The prevalence of different HPV genotypes at anal, cervical, and oral sites is shown in P = 0.049), 18 , and 58 , whereas there were no differences in the distribution of other LR and HR genotypes according to gender.Overall, men were more likely to harbor genotypes 11 .Up to 37% of men and 20% of women showed multiple genotypes. Patients with HR-HPV more often harbored multiple HPV strains compared with those with LR-HPV  and cervical (women) specimens. A total of 7/180 anal specimens (3.8%) and 3/97 (3%) cervical specimens were unsatisfactory for cytologic classification and were excluded from the analyses. P = 0.0002). Two variables were associated with a higher risk of atypical cytology in a univariate analysis: being infected through the homosexual route (odds ratio (OR): 4.05; 95%CI: 1.88–8.69) and harboring HR-HPV . Advanced age  and being on HAART  were associated with a lower risk. After controlling for demographic and HIV-related factors , only subjects harboring HR-HPV remained significantly at risk for atypical cytology compared with HPV-negative individuals (adjusted odds ratio (AOR): 3.48; 95%CI: 3.54–20.47)  showed atypical cytology; 11 patients  had HSILs, 62 (35%) had LSILs, and 10 (5%) had ASC-US. A total of 76/83 men with atypical cytology (91.5%) were HPV positive, and 63 (76%) harbored HR-HPV strains. HR-HPV was more frequently detected in men with more severe dysplasia  . in situ squamous cell cancer). Of these 34 women, 29 (85%) were HPV positive, and 20 (59%) harbored HR-HPV genotypes. HR-HPV was detected more frequently in women with more severe atypical cytology . In the univariate model, women infected via the sexual route were more likely to have atypical cytology ; no other demographic or clinical characteristics were associated with occurrence of atypical cytology. The detection of both LR-HPV and HR-HPV was associated with atypical cytology . In the multivariate model, only the presence of either LR-HPV or HR-HPV was confirmed to be associated with atypical cytology   women showed abnormal cervical cytology  .P = 0.09).Overall, men showed a nonstatistically higher risk of SILs compared with women  in a population of HIV-positive individuals in a high-income country. The overall prevalence of HPV infection in our cohort was 72.6% ; HPV was more frequent in men than in women (81% versus 58%), and oral localization was detected in up to 20% of individuals. Our results are consistent with those of previous studies conducted in HIV-positive populations, in which the prevalence rates of HPV infection were 48%–76.9% , 20 in wAs expected, these prevalence rates are higher than those observed in the general population –27. ManyThe estimates of oral HPV prevalence in the literature are highly variable , and it  In terms of viral genotypes, it is interesting to note that no concordance in HPV genotype was found in our cohort in concomitant infections at both oral and genital sites, which occurred in 38.8% of HPV-positive individuals, and this result is consistent with previous studies , 21. Dif3) or moderate (200–500 cells per mm3) CD4 T-cell count but not in women with a low CD4 T-cell count [Regarding the immunovirological profile of our cohort according to HPV serostatus, we observed that HPV-coinfected individuals showed higher median CD4 T-cell counts compared with HPV-negative subjects. These findings are in contrast with other studies  and mighll count . It coulWe did not find any associations between HAART usage and HPV infection. Data regarding the impact of HAART on HPV infection and HPV-related cervical abnormalities are inconsistent or controversial , 34. TheHigh-risk HPV genotypes are associated with the development of cancer . GloballRegarding cytological data, only 3% of the total specimen was not appropriate for diagnoses; this percentage is very low and could not affect the results, in our opinion. Concerning anal dysplasia, SILs were diagnosed in 47% of men; our results are in line with those of previous reports showing a 34%–71% prevalence of abnormal anal cytology , 37, 38.Both LR-HPV and HR-HPV genotypes were associated with atypical cytology in women of our cohort, with an 85% prevalence of HPV infection in 59% of cases characterized by HR genotypes. Data available on Italian women routinely screened for cervical dysplasia suggest that the prevalence of HR-HPV and LR-HPV infection is lower than in our cohort . Notably, up to 53% of men and 24% of women harbor HR-HPV without any cytologic damage; further studies are required to better evaluate this population of healthy HR-HPV carriers. The absence of oral mucosal abnormalities despite a 20% prevalence of HPV infection at the oral site is in contrast with recent studies in which HIV-positive individuals more frequently displayed an oral mucosal abnormality  than theThe main findings from this cohort study are the high prevalence of HPV and high-risk HPV genotypes in our cohort of HIV-positive men and women who are asymptomatic for genital distress. Of major concern is that almost half of the subjects suffer from genital or anal dysplasia with different degrees of severity. The long-term followup of subjects with dysplastic lesions will clarify their possible evolution in the HIV setting. On the basis of these results, we suggest mandatory screening for both HPV and related lesions in all HIV-positive subjects and the possible implementation of vaccination studies and programs in HIV-positive/HPV-negative patients.Questionnaire on sexual behavior: self-reported questions on number of sexual partners, type of sexual intercourse and history of sexually transmitted diseases.


In positive psychology optimal wellbeing is considered a broad, multi-dimensional construct encompassing both feelings and functioning. Yet, this notion of wellbeing has not been translated into public health. The purpose of this study is to integrate public health and positive psychology to determine associations between lifestyle behaviours and optimal wellbeing in a diverse sample of New Zealand adults.A web-based survey design was employed to collect data. Participants reported on their wellbeing and lifestyle behaviours including nutrition, exercise, sedentary behaviour, and sleep. Optimal wellbeing was calculated using a multi-dimensional scale designed to mirror the internationally recognised diagnostic criteria for mental disorders. Binary logistic regression was used to calculate associations between 10 lifestyle behaviours and optimal wellbeing.n = 9514), 24 % met the criteria for optimal wellbeing. Compared to reference groups, the association with optimal wellbeing was greater for those who reported exercising ≥7 times/week  and sitting “almost none of the time” . Optimal wellbeing was lower for those reporting restless sleep “almost all of the time”  and consuming sugary drinks 5–6 times/week .Of the total sample (Public health and positive psychology were integrated to provide support for a relationship between lifestyle behaviours and a multi-dimensional measure of optimal wellbeing. It is likely this relationship between lifestyle behaviours and optimal wellbeing is bidirectional giving rise to the debate that holistic approaches are needed to promote positive health. In 1946 the World Health Organization defined health as “a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity” –4. HowevRecognition that a fundamental shift was needed to study wellbeing in its own right has led to the emergence of the positive psychology field , 6. WithOnly recently have multi-dimensional measures of optimal wellbeing emerged which can be used to categorically determine those with the highest levels of wellbeing , 8. In tPositive psychologists recognise that there is a need to identify characteristics and behaviours which are associated with optimal wellbeing , 10. NonAt an epidemiological level, an integrative approach to understanding associations between lifestyle behaviours and optimal wellbeing is needed. If associated, promoting lifestyle behaviours may provide an opportunity for increasing wellbeing, or vice versa. Identifying lifestyle behaviours that are associated with optimal wellbeing will provide a useful step in guiding future research and interventions aimed at promoting positive health. The purpose of this study is to integrate measures from public health and positive psychology to determine (1) the proportion of a large, demographically diverse sample of New Zealand adults meeting the criteria for optimal wellbeing and (2) associations between lifestyle behaviours and optimal wellbeing. This study will contribute to the limited research on lifestyle behaviours and multi-dimensional measures of optimal wellbeing.Data for this cross-sectional study were obtained from the Sovereign Wellbeing Index (Round 1); a survey on the health and wellbeing of a large, demographically diverse sample of New Zealand adults . A web-bThe web-based survey design was chosen as it offered a number of advantages over traditional data collection modes (i.e. door-to-door or computer assisted telephone interviews). These advantages include the relative cost-effectiveness of the approach, the ability to overcome geographical constraints, and the minimisation of errors associated with data entry . Recent A commercial market research company  was contracted to administer the web-based survey. Participants were recruited from the SmileCity database; the largest commercially available database in New Zealand. The database comprises 247,675 active members recruited through both offline (51 %) and online (49 %) sources .The target sample size for the current study was 10,000 participants. The sample size was determined partly by financial constraints, and partly to obtain a reasonable precision of estimates. Eligible individuals included SmileCity database members aged over 18 years who had not participated in a survey within the last 7-days. There were no further exclusion criteria.Email invites—with a link to the survey—were sent to 38,439 individuals randomly selected from the 229,032 eligible individuals. The survey was open to potential participants for 7-days. No follow-up invites were sent to individuals who did not complete the survey within the specified timeframe. All participants provided informed consent prior to entering the survey.The web-based survey included 134 questions on wellbeing, health and lifestyle, and socio-demographics. To enable international and national comparisons, the wellbeing component primarily comprised questions drawn from the European Social Survey (Round 6)  whilst tI love learning new things’ and ‘There are people in my life who really care about me’. These items were replaced with ‘To what extent do you learn new things in your life’ and ‘To what extent do you receive help and support from people you are close to when you need it’, respectively [Optimal wellbeing was treated as a binary variable. The ten items ; and four out of five features of positive characteristics ; and three out of four features of positive functioning  [The ten items used to measure optimal wellbeing combined both hedonic (feelings) and eudaimonic (functioning) aspects of wellbeing . The iteips ≥ 4) . Table 1Self-reported socio-demographic variables including gender, date of birth, ethnicity, and household income were collected as part of the web-based survey. In accordance with Statistics New Zealand’s Statistical Standard for Ethnicity, respondents were provided with the option of selecting multiple ethnic response categories . ResponsTen lifestyle behaviours were included in the analysis including breakfast consumption, sugary drink consumption, fruit intake, vegetable intake, smoking, alcohol consumption, exercise, sedentary behaviour, sleep quality, and body mass index (BMI).never, 1-2 days, 3-4 days, 5-6 days, 7 days); how often during the past week they drank sugary beverages ; on average how many servings of fruit they had over the past week ; and on average how many servings of vegetables they had over the past week  [yes, no) [ [.Questions to measure breakfast consumption, sugary drink consumption, fruit intake, vegetable intake, smoking, and alcohol consumption were drawn from the New Zealand Health Survey (2006), an annual door-to-door survey conducted by the Ministry of Health . Respondngs/day) . For smoyes, no) . Alcoholes/week) .I didn’t exercise, 1-2 times, 3-4 times, 5-6 times, ≥ 7 times) [never, seldom, sometimes, often, always) [none or almost none of the time, a little of the time, some of the time, most of the time, all or almost all of the time).Exercise was measured using a single item exercise frequency question which asked participants to report how often during the past week they exercised (7 times) , 27. Sed7 times) . Respons always)  to reflenone or almost none of the time, some of the time, most of the time, all or almost all of the time).Sleep quality was assessed using a question drawn from the European Social Survey (Round 6) Survey . The quekg/(heightm2). World Health Organization thresholds were used to categorise BMI as: underweight (≤18.4), normal weight (18.5–24.9), overweight (25.0–29.9), and obese (≥ 30.0) [Body mass index was derived using self-reported height and weight measures and was calculated as weight(≥ 30.0) .With the exception of BMI, all lifestyle variables are reported as per their original response scales.Optimal wellbeing was treated as the dependent variable. Participants’ data were, therefore, only included in the final analyses if a response was provided for each of the ten items used to calculate optimal wellbeing. Binary logistic regression analysis was used to determine associations between both demographic factors and lifestyle behaviours and optimal wellbeing (IBM SPSS Statistics version 19 for Windows). Crude, partially adjusted , and fully adjusted  odds ratios were calculated. Bootstrapped 95 % confidence intervals (CI) were calculated using 1000 samples. The alpha was set at 0.05 to determine statistical significance. Missing data for lifestyle behaviours and socio-demographic variables were excluded pairwise.n = 12,170) and the completion rate was 82 % (n = 9962)  of the sample met the criteria for optimal wellbeing .The trend across the three models indicates the likelihood of achieving the criteria for optimal wellbeing increases with age. The fully adjusted odds ratios show those aged 70–79 years were significantly more likely to report optimal levels of wellbeing compared to those aged less than 20 years  but was negated for Asian people.No association was observed between ethnicity and achieving the criteria for optimal wellbeing in the crude model. However, when adjusting for age, gender, and household income, Asian people and Maori/Pacific people were significantly more likely to meet the criteria for optimal levels of wellbeing compared to European/Other people. In the fully adjusted model the association between ethnicity and optimal wellbeing remained for Maori/Pacific people  and 1.84  times more likely, respectively, to reach the criteria for optimal wellbeing compared to those in the lowest income tertile.Household income was significantly associated with optimal wellbeing in each model. In the fully adjusted model those in the middle and highest income tertiles were 1.30  of achieving the criteria for optimal wellbeing, compared to those who reported that they do not consume sugary drinks.Sugary drink intake was inversely and significantly associated with optimal wellbeing in the crude and partially adjusted models. In the fully adjusted model consuming sugary drinks 5–6 times per week was associated with a decreased likelihood  and 5-6 days per week  were associated with a decreased likelihood of being in the optimal wellbeing group.Compared to those that reported eating breakfast daily, eating breakfast 1-2 days per week  and partially adjusted  models; however, these associations were negated in the fully adjusted model.Compared to smokers, being a non-smoker was associated with an increased likelihood of reaching the criteria for optimal wellbeing in the crude , partially adjusted , and fully adjusted  models.Compared to those that consume alcohol up to four times per month, drinking alcohol monthly or less was significantly associated with a decreased likelihood of being in the optimal wellbeing group in the crude  increased likelihood of being in the optimal wellbeing group in the fully adjusted model.Exercise was positively and significantly associated with achieving the criteria for optimal wellbeing in all three models. Compared to those who reported doing no exercise, exercising seven or more times per week was associated with a 1.61  times more likely to meet the criteria for optimal wellbeing.An inverse relationship between sedentary levels and optimal wellbeing was observed in all three models; decreases in sedentary behaviour were associated with an increased likelihood of meeting the criteria for optimal wellbeing. In the fully adjusted model, those who reported sitting none or almost none of the time during the past week were 1.87  likelihood of being in the optimal wellbeing group compared to those reporting restless sleep none or almost none of the time.In all three models restless sleep was negatively associated with optimal wellbeing. In the fully adjusted model, having restless sleep all or almost all of the time was associated with a significantly decreased . One possible explanation for this somewhat unexpected finding is that those occasionally drinking may be doing so in social environments thereby benefiting from social interaction and enhanced positive relationships. Finally, consuming sugary drinks 5-6 times per week was associated with a 0.73-fold decreased likelihood of achieving the criteria for optimal wellbeing. Limiting sugar is, therefore, likely to have implications from both a health and wellbeing perspective.To a lesser degree, associations between optimal wellbeing and breakfast consumption, sugary drink intake, BMI, and alcohol consumption were also observed in the current study. Similar associations between breakfast consumption and happiness have been observed previously . In our The relationship between lifestyle behaviours and optimal wellbeing is complex and likely to be bidirectional. On the one hand, if individuals feel optimistic, energetic, confident, and supported they are probably more likely to engage in positive lifestyle behaviours . AlternaIt is pertinent to note that three quarters of the sample in the current study were not meeting the criteria for optimal wellbeing. It is therefore evident that further efforts need to be made promote and increase optimal wellbeing. Whilst the causal relationship between lifestyle behaviours and optimal wellbeing cannot be determined from our data, existing evidence supports the claim that the relationship is likely to be bidirectional. Our findings, together with the literature, provide support for holistic interventions which integrate the promotion of lifestyle behaviours and the dimensions underpinning optimal wellbeing . Our research shows the lifestyle variables which should be targeted in such interventions include sleep, exercise, and sedentary behaviour, and to a lesser degree sugary drink consumption and breakfast intake.The findings from this study should be considered in light of the limitations. Firstly, although the web-based survey design offered a number of advantages, the response rate was low (32 %). Comparisons to the estimated resident population during the September 2012 quarter indicate our sample was slightly over-represented by younger adults and slightly under-represented by those aged over 60 years. Secondly, the current study relied on self-reported lifestyle behaviours, rather than observational measures. There is therefore a possibility that individuals were subject to social desirability bias. Finally, the cross-sectional nature of the data precludes the ability to infer causation. The relationship between lifestyle behaviours and optimal wellbeing is complex and likely to be bidirectional. Intervention and mechanistic studies are required to further progress our understanding of this relationship. The findings from this study provide a starting point for determining the most pertinent lifestyle variables to include in such research.In this study, two research fields—positive psychology and public health—have been integrated to examine the relationship between lifestyle behaviours and optimal wellbeing. The current study contributes to the limited wellbeing research in New Zealand to show almost a quarter of a large and demographically diverse sample of New Zealanders are meeting the criteria for optimal wellbeing. This study also extends current international knowledge to show sleep, exercise, and sedentary behaviour, and to a lesser degree breakfast consumption, sugary drink intake, BMI, and alcohol consumption are associated with a broader, more complex notion of wellbeing. It is likely this relationship between lifestyle behaviours and optimal wellbeing is bidirectional giving rise to the debate that holistic approaches are needed to promote positive health.


HPV infections can cause substantial burden in females and males as it is associated with several genital cancers, in addition to genital warts. Traditional economic evaluations often focus on quantifying cost-effectiveness, however, it is increasingly recognized that vaccinations may generate broader benefits not captured in cost-effectiveness analysis. Τhe aim of this study was to evaluate the broader economic consequences associated with HPV vaccination in males and females and to conduct a lifetime cost-benefit analysis of investing in universal vaccination in Germany from the perspective of government. Methodologies from generational accounting, human capital and health economics were combined to estimate the broader economic consequences of HPV vaccination including the fiscal impact for the government. A cohort model was developed simulating the medical costs and average lifetime fiscal transfers between the government and 12-year-old immunized and non-immunized males and females. To estimate tax revenue attributed to vaccination-related changes in morbidity and mortality, direct and indirect tax rates were linked to differences in age- and gender-specific earnings. Based on HPV vaccination costs, the base case cost-benefit analysis demonstrated that investing €1 in universal HPV vaccination could yield €1.7 in gross tax revenue over the lifetime of the cohorts. After taking into consideration the governmental transfers, universal HPV vaccination in Germany could result in incremental positive net discounted taxes (i.e. tax revenue-transfers) from €62 million for the German government. The vaccination of males and females with the quadrivalent HPV vaccine is likely to have positive effects on public finances.The online version of this article (doi:10.1186/s13561-015-0054-6) contains supplementary material, which is available to authorized users. The human papillomavirus (HPV), in particular subtypes 6, 11, 16 and 18, is responsible for a number of conditions in both males and females including genital warts (GW) as well as vaginal, vulvar, cervical and anal cancers in females and penile and anal cancers in males . In addiIn Germany, since 2007, HPV vaccination has been recommended and funded for all females aged 12 to 17, in combination to a yearly cervical cancer screening starting from age 20. Several cost-effectiveness analyses suggested that vaccinating females against HPV is a cost-effective strategy both in Germany and elsewhere . PreventThe acquisition of vaccines for national vaccination programs are unique among healthcare purchases in that stakeholders often include treasury and other federal ministries necessary for procurement decisions , 8. To iTo estimate the broader economic consequences of HPV vaccination in males and females we estimated how resulting changes in HPV related morbidity and mortality may influence government fiscal accounts based on the efficacy profile for the quadrivalent HPV vaccine under a fixed economic scenario (“ceteris paribus”). Three analytic frameworks stemming from the health economic, economic and public economic theory were employed to quantify the economic impact of immunization and to compare the benefits and costs associated with HPV vaccination in Germany. The analytic frameworks utilized were health-care budget impact analysis, human capital economics, fiscal modelling and generational accounting. By combining these frameworks it was possible to estimate how preventable HPV-related morbidity and mortality would generate both short and long-term societal and fiscal consequences for the German government.The health-care budget impact analysis estimated how changes in HPV related mortality and morbidity influence short term and long term health-care public spending. The lifetime human capital of immunized and non-immunized male and female cohorts was projected to determine how changes in HPV related morbidity and mortality affect lifetime earnings. The government direct and indirect tax burden was then applied to wages to determine the expected fiscal revenues in terms of gross tax. Following the principles of generational accounting  the average lifetime transfer costs and tax revenues attributed to changes in morbidity and mortality resulting from HPV vaccination were also estimated. To avoid double calculations of health-care costs, non-HPV related health expenditure was not included in the analysis. In addition, educational costs were not considered in this analysis since the level of mortality and morbidity during the first years of life for both immunized and non-immunized cohorts were considered as similar. For the three analytic approaches, only those factors that have direct influence on government fiscal accounts were assessed.The analysis was conducted for a single cohort of 12 year old males and females. The latter age cohort was analyzed in order to quantify the benefits and costs for the German government from the prospective annual vaccination against HPV. Hence, this study economically assesses the hypothesis that, according to the German vaccination guidelines, each year the cohort of males and females that enters the age of 12 will be included in a universal vaccination program.A prospective single-cohort model was developed in Microsoft Excel. The model simulated the lifetime of 12 year old males and females with and without vaccination against HPV. Survival was projected based on lifetable methods hence, based on the current life expectancy in Germany . The cohThe age-specific incident cases of GW, CIN and HPV-related cancers were multiplied by the, per case, medical costs. The age and disease specific deaths were multiplied by the projected loss of earnings and tax revenue for the remaining statistical life. The above two were summed to estimate the burden of disease (BOD) with and without immunization for the society and the government .Firstly, a fiscal cost-benefit analysis (CBA) was conducted following a “government perspective”. The gross lifetime tax revenue loss, as a result of HPV-related deaths, of the immunized and non-immunized cohorts of males and females was projected. The projected lifetime tax revenue loss as a result of HPV-related deaths and the HPV–related health care costs were considered a measure of the fiscal BOD. The incremental BOD between the immunized and non-immunized cohort of males and females was considered as the benefit of vaccination which was subsequently compared with the cost of vaccinations to establish the net benefit [i.e. Benefits of vaccination – vaccination investment] and benefit cost ratio (BCR).A societal CBA was also conducted based on the societal BOD difference for the immunized and the non-immunized cohorts. The societal analysis took into account the foregone consumers surplus as a result of premature mortality. Foregone surplus refers to the productivity loss, in terms of lost earnings, for the remaining statistical life of individuals that die as a result of HPV infection. Thus, in the societal analysis in order to calculate the societal BOD, HPV-related deaths were multiplied by the present value of the remaining lifetime earnings lost due to premature deaths. The societal BOD included the HPV-related medical costs as a result of the disease and the productivity loss as a result of premature deaths. In the above CBAs, a positive benefit minus cost difference and a BCR greater than one signifies a positive economic effect for vaccination.Then, a government perspective analysis was conducted applying the “generational accounting” methodology to calculate the incremental net discounted tax (lifetime gross tax minus the lifetime transfers) . This anThe net discounted tax analysis uses a longitudinal timeframe that constructs the average life course for immunized and non-immunized cohorts. The model simulates how the cohorts influence fiscal accounts both in terms of lifetime taxes and government transfers received based on changes in morbidity and mortality attributed to HPV vaccination. The modified “generational accounting” framework applied here combines the three modelling approaches mentioned above to capture the influence of HPV vaccination on net discounted tax for government. A positive incremental net discounted tax signifies that the government has a benefit from vaccination after taking into account the additional transfer costs associated with increased survival. The mathematical details of the aforementioned economic appraisals are illustrated in the Additional file The cohort size of 12 year olds was set equal to the size  used in previous economic analyses of HPV vaccination in Germany . EvidencVaccine efficacy was obtained from the clinical trials of the quadrivalent HPV vaccine (Gardasil SmPC). The efficacy of the vaccine was weighted for the mortality and morbidity attributable to the HPV serotypes included in the vaccine i.e. HPV6/11/16/18  sensitivity analysis to most parameters modeled as well as a variation around discount, inflation and wage productivity rates. Additional analyses were conducted to evaluate a scenario considering a 3 doses vaccine course (previous vaccination schedule) and inclusion of head and neck cancers and sick days lost based on reported data for Germany .In the base-case analysis, over the lifetime of the male and female cohorts, the analysis demonstrated that vaccination against HPV (with a coverage rate of 55 %) prevented 857 HPV-related cancer deaths in Germany. Vaccination also prevented 1527 cervical cancer cases, 286 anal cancer cases, 228 vaginal cancer cases and 116 vulvar cancer cases. In addition, vaccination resulted in 45,809 less cases of genital warts and 127,464 cases of CIN I-III for the lifetime of the cohort.For the combined population of females and males the results showed that HPV vaccination resulted in reducing both the fiscal BOD in terms of the present value of lifetime gross tax loss due to premature mortality and the societal BOD in terms of the present value of lifetime earnings or productivity loss due to premature mortality. In addition, vaccination resulted in the reduction of HPV-related medical costs Table .Table 2EWhen comparing the investment costs and the benefits of vaccination from a government perspective, the fiscal CBA suggested that €1 invested in universal HPV returns €1.7 in terms of averted tax revenue loss and prevented HPV-related medical costs. Female vaccination yielded, as expected, higher returns compared to male vaccination. Investing in male vaccination may offset almost one third of the investment costs whereas, for females the returns are 3-fold the investment cost  resulted in positive fiscal BCR (>1). If three doses of vaccine were administered the BCR would decrease to 1.3. An additional scenario included the indirect costs of HPV related diseases in terms of sick days lost. As expected the results are more favorable for the vaccination compared to the basic scenario. Finally, the scenario including vaccine potential impact against head and neck cancers (for which the vaccine has currently no indication) resulted in increasing the fiscal BCR from 1.7 to 2. The latter influence of the results can be explained from the reduction of male mortality and the relatively higher lifetime earnings of males.Previous recommendations by the German Standing Committee on Vaccinations have found that vaccinating adolescent females against HPV is a cost-effective option in Germany . MoreoveThe distinction in the analysis described here is that we consider tax financed health systems to be within the government sphere; hence changes in HPV related morbidity and mortality can influence government transfers. This analysis demonstrates that investments in HPV universal immunization yield positive benefits for government in terms of cost savings and increased tax revenue. The fiscal CBA estimated that investing in universal HPV vaccination could generate a positive rate of return, equal to a BCR of 1.7 for every Euro spent on immunization by the German government. Moreover, this study showed that from a societal perspective, surplus societal benefits  could be achieved by vaccinating males and females against HPV.In recent years, preventative healthcare budgets, which account for approximately 3 % of total healthcare expenditures in Europe have been decreasing, suggesting a need to highlight the health and economic importance of prevention . Indeed,The analysis described here applies a lifetime horizon and financial metrics to estimate fiscal consequences associated with HPV immunization and suggests that, over a lifetime span, the vaccination of males and females offers positive fiscal benefits. There are many inherent weaknesses in making long-term projections based on current macroeconomic parameters due to uncertainty regarding the future. In this respect, the results described here should not be seen as a precise forecast of the future. Rather, the fiscal analysis reflects a potential scenario based on current economic and epidemiological conditions, that future changes in unemployment, growth rates, tax burden, government transfers or inflation could either positively or negatively influence the findings described here. This is particularly important to consider in relation to the static incidence rates applied in our analysis and failure to account for herd immunity which could influence incidence rates and the likely benefits attributed to vaccination. Consistent with the generational accounting framework on which our analysis is based, we have held parameters constant over time. We acknowledge this weakness but in the absence of knowledge of the future, the approach is useful for making policy decisions today, and, in this respect, is not different than any other funding or policy decisions made by governments.In addition, the modelled mortality and morbidity data in this study, do not take into account socio-economic status which may influence HPV incidence and mortality and treatment seeking patterns that, in turn, may affect labour productivity and tax revenue loss as measured by the human capital and generational accounting methods, respectively. Moreover, with the exception of cervical cancer, case-fatality rates were used to estimate age-specific mortality. It should also be noted that the results presented in this study are specific to the German macroeconomic setting. Given cross-country differences in macroeconomic parameters and the health system production functions, it is expected that the benefits from HPV immunization vary across countries. Further research should focus on the generalizability of the results to other country-settings.Probabilistic sensitivity analysis (PSA) is commonly applied in cost-effectiveness analysis to inform healthcare stakeholders of parameter uncertainty. Because our modelling approach does not follow the conventional “health service” cost-effectiveness perspective, it seeks to inform an audience within government about the fiscal impact of investing in immunization programs, and epidemiological outcomes have been translated into fiscal gains and losses for government. The model is based on a modified generational accounting framework which informs government about costs and consequences of investments in technology. As PSA is not a feature of this modelling approach, and not relevant to the target audience for this work, it has not been applied in our analysis. It is conceivable that PSA could be applied however, in the absence of distributions for each variable, arbitrary ranges can only be used which may provide limited uncertainty analysis outcomes. The univariate sensitivity analysis applied in this model was deemed as adequate for both understanding key areas of uncertainty, and informing stakeholders of the potential gains and losses from investing in HPV vaccination.Decision-making regarding funding of vaccines is a complex process involving numerous government stakeholders and health service officers. Even when vaccines have been approved by national advisory groups, it is acknowledged that funding should be independently sought from finance ministries . UnderpiConsidering the broader economic consequences of vaccine preventable conditions suggests that changing population health through vaccination can offer economic advantages for government in the form of future tax revenues and potential savings attributed to social care. Consequently, investing in vaccination can be viewed as a public investment stimulating economic growth and influencing government finances , 24. TakThe framework described here estimates how saving lives and influencing HPV infections in males and females can generate fiscal benefits for government. This raises questions about how to apply a fiscal accounting framework in healthcare decision-making when healthcare resources are often influenced by unmet need, burden of illness, affordability, equity and sometimes politics. While it is tempting to only invest in those strategies that yield benefits for government, it is questionable whether it is justifiable to exclude treatment from some groups on the basis of having a low fiscal return for government. Clearly this is not the case as resources are allocated for many interventions in terminal conditions that generate no fiscal benefits for government. On this basis, we do not expect decision-makers to abandon the core principles of decision-making which include unmet need, equity and fairness. However, this approach can be supplementary to existing analytic frameworks used by decision-makers to consider a broader range of benefits from the perspective of government. This can be particularly important for tax financed health systems that rely on younger, healthy generations to continue paying for the healthcare needs of older generations .


Oral manifestations (such as warts) of HIV infection are evident of disease progression, occurring in 30–80% of affected population. Recent evidence indicates that Human Papillomavirus (HPV) related diseases are increased in the oral cavity of HIV seropositive individuals irrespective of HAART. This study was undertaken to evaluate prevalence of oral HPV infection in Indian HIV seropositive women with/without oral warts.http://pave.niaid.nih.gov/#pavic.Detection of HPV was carried out from saliva of 60 women divided into equal groups of HIV seropositive with/without warts and age/sex matched healthy controls with/without warts by nested PCR using consensus primers MY09/11 and GP5+/6+ for L1 gene followed by sequencing and sequence analysis. The sequences were typed using the HPV L1 typing tool available on Only one sample was detected to be positive for HPV  and was from the HIV seropositive women with warts group. The HPV serotype was determined to be the low risk non-oncogenic HPV Type 6 by the L1 typing tool and multiple sequence alignment.While this was a preliminary study to determine prevalence of HPV in HIV seropostive women, our study has determined a positive correlation with multiple warts and oral sex as factors associated with presence of HPV. Our study also questions whether HAART has a beneficial impact on HPV induced cancer. We are of the opinion that this study is the first of its kind in Indian women and emphasize that extensive studies are necessary to establish the incidence of HPV in HIV seropositive population from India.


The causes of lung cancer in never-smokers remain unclear. The potential contribution of human papillomavirus (HPV) to the carcinogenesis of non-small cell lung cancer (NSCLC) has been reported. In 2008, a prospective registry of never-smokers with NSCLC was established at the Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan. Never-smokers with NSCLC were consecutively enrolled onto the registry. Of these patients, 114 with large tumor specimens, the majority of which were surgical tissues, were selected. In total, 23 of the most clinically relevant HPV types were assayed using polymerase chain reaction amplification of the viral genome. Following exclusion of samples with suboptimal quality, DNA was extracted from 96 formalin-fixed paraffin-embedded samples. These 96 cases consisted of 82 females (85.4%) and 14 males (14.6%), with a median age of 67 years . Almost all cases (93.8%) were of the adenocarcinoma histological subtype. Despite confirmation of the quality and amount of DNA, HPV type 6 was detected in only one case (1.1%). Furthermore, no other samples examined were positive for any other HPV types. The results therefore suggest that HPV does not play a major role as the driving oncogenic event in never-smokers with NSCLC. While lung cancer is the leading cause of cancer-related mortality and is predominantly caused by tobacco smoke, ~25% of all lung cancers worldwide are not attributable to tobacco smoke . In factA meta-analysis previously demonstrated that the prevalence of HPV in lung cancer is highly variable around the world, with higher HPV frequencies observed in East Asian countries compared with European countries . HoweverIn 2008, a prospective registry of never-smokers with NSCLC was established at the National Hospital Organization Kinki-Chuo Chest Medical Center. Subsequent to obtaining written informed consent, patients were enrolled prospectively and consecutively to determine if they had newly diagnosed or histologically or cytologically confirmed NSCLC. The patients were never-smokers (<100 cigarettes/lifetime) and had tumor tissue samples available for analysis. All patients were requested to complete a detailed questionnaire, including confirmation of never-smoker status and any family history of cancer and passive smoking status . A totalThis study was approved by the Institutional Review Board of the National Hospital Organization Kinki-Chuo Chest Medical Center.HPV genotyping was performed using a polymerase chain reaction (PCR)-based microarray system  to detect 23 HPV types, including high-risk , low-risk or risk-unknown types . This system uses type-specific primers and probes that are designed to detect the E2, E6, E7, L1 and L2 genes. The target HPV-DNA was amplified by PCR using a Mastercycler gradient . PCR was performed in a total volume of 20 μl, containing multiple primers for each of the HPV types  FastStart Taq DNA polymerase , dNTP mix, dUTP labeled with Cy3 and specimen DNA. A total of 100–1,000 ng/3 μl specimen DNA was used in each reaction. PCR conditions were as folows: 4 min at 95°C, followed by 40 cycles of 95°C for 30 sec, 65°C for 30 sec, 72°C for 1 min, and one cycle of 72°C for 7 min. The DNA samples were then applied to HPV genotyping arrays and hybridization was performed at 65°C for 1 h. Samples were washed and dried, and analysis was performed using a micro-array scanner ((EGFR) mutations (63.4%), five KRAS mutations (5.4%) and four EML4-ALK rearrangements (4.3%).Following the exclusion of the samples with suboptimal quality from the 114 patients, DNA was successfully extracted from 96 formalin-fixed paraffin-embedded surgical tissues. The clinical characteristics of these 96 cases are summarized in EGFR mutation (exon 19) with wild-type KRAS and ALK. The patient had previously undergone surgery twice for condyloma acuminatum, and had stage I adenocarcinoma. During a 25-year period, the patient was subjected to environmental tobacco smoke exposure . At five years post-surgery, the patient experienced a recurrence of the lung cancer. Following treatment with gefitinib (250 mg/day) for one year, the patient succumbed to brain metastasis subsequent to several rounds of chemotherapy.HPV type 6 was detected in only one case (1.0%) among the 96 tumor samples. The patient was a 49-year-old female who presented with an No other patients examined were positive for any HPV types, including high-risk , low-risk or risk-unknown types .In the present study, a low-risk HPV type was evident in one case among 96. However, no HPV of any type was detected in any other tumors. These results suggest that HPV does not play a major role as the driving oncogenic event in lung cancer in never-smokers in Osaka, Japan.et al demonstrated the presence of HPV in the exhaled breath condensate of lung cancer patients (It is known that HPV types essentially cause all human cervical cancers . During patients .Although the data from the present study suggest that HPV involvement in lung cancer is unlikely in never-smokers, the issue remains controversial. According to previous studies, the prevalence of HPV is not uniform ,17. RegiThere are several advantages to the present study. Firstly, the data in this study is accurate, as it was obtained by detailed questionnaires and interviews of the patients and their families. Secondly, the HPV genotyping used a high precision test and included a range of 23 HPV types, including low- and high-risk types. In order to further clarify HPV carcinogenesis, a nationwide prospective study of the viral molecular epidemiology of Japan is required. This should consider the association between viral infection and carcinogenesis, and regional differences in HPV prevalence .In conclusion, a low-risk HPV type was evident in one patient sample, and no other lung cancer tumors that were examined were positive for any HPV types in the never-smokers. These results suggest that HPV does not play a major role as the driving oncogenic event in never-smokers in Osaka, central Japan.


Type-specific association was observed for genital HPV infection and HPV seropositivity among women but not among men. A positive correlation between the number of lifetime sexual partners and positivity for oncogenic HPV DNA and/or antibodies was found in men but was absent in women. Among 762 couples, the presence of HPV DNA and/or antibodies in one partner was positively associated with the identical HPV type in the other partner. These findings may reflect a site-specific natural course of HPV infection and further understanding of the epidemiology of HPV.Data on simultaneous analysis of human papillomavirus (HPV) DNA and serology and the correlations within a single general population are limited. Among 1603 men and 2187 women enrolled from rural China, serum antibodies against bacterially derived GST-L1 fusion proteins of HPV were assessed with multiplexed serology and HPV DNA was evaluated with PCR-based sequencing. Few subjects were dually positive to HPV DNA and serum antibodies for any HPV (6.6% of men and 3.1% of women). The proportion of men ever having been infected with any HPV (DNA and/or antibody positive) was higher than that of women (71.0%  Genital human papillomavirus (HPV) infection which is mainly sexually transmitted is an etiologic factor for malignant lesions of the cervix, vagina, vulva, and penis, and genital warts3However, until now much remains to be known about simultaneous status of HPV DNA and serology and its associated factors within given general populations worldwide, especially in men55Previously, we reported an overall seroprevalence of 64.8% for HPV-3, 6, 11, 16, 18, 45, 52, 57, 58, and/or 75 in 5548 healthy males and females aged 25–65 in rural Chinavs. 1.6%) (vs. 0.1%).Among 4996 eligible subjects, 3790 (75.9%) participants showed valid results for genital HPV DNA and serological outcomes. The chief reasons why the remaining 1206 individuals who were generally more likely to be younger men, were not included in the analysis, were either failure to respond due to employment outside of Anyang, or negativity for beta-globin. Among these 3790 subjects, the median age was 44 years  and the male-female ratio was 0.7 (1603/2187). Most subjects had less than 9 years of education (91.7%) and were married or cohabiting with a partner (94.9%). More males habitually worked for long periods outside of their local areas of residency as compared to females (27.9% s. 1.6%) . Cigaretvs. 65.2%, P < 0.001). The same pattern was seen for oncogenic HPV  and HPV-16 , which was the most prevalent type for both genders. Of the other four oncogenic HPV types evaluated, the proportions of HPV positivity ranged from 5.4% (HPV-52) to 10.2%  among men and ranged from 3.8% (HPV-52) to 11.0% (HPV-58) among women.Both overall and age-specific HPV seroprevalence was higher than DNA prevalence . In termThe percentage of HPV DNA positive men who were positive for HPV antibodies of the same oncogenic type was 11.3% among men and 14.3% among women (Data not shown). Regarding type-specific positivity for HPV antibodies of the same oncogenic type as the HPV DNA, the proportions were 0.0% for HPV-45, 5.6% for HPV-18, 8.9% for HPV-16, 27.3% for HPV-58 and 33.3% for HPV-52 among men. The proportions were 0.0% for HPV-18, 12.5% for both HPV-16 and HPV-52, 20.0% for HPV-58, and 25.0% for HPV-45 among women.Ptrend = 0.017) and was characterized by a highest peak value at 56–60 years (36.8%). The age-stratified prevalence for oncogenic HPV was relatively constant with age among men except for a peak at 46–50 (42.5%).The pattern of the age-related HPV positivity (DNA positive and/or antibody positive) was driven mainly by HPV seroprevalence . The oncP = 0.066). However, among males, none of these correlations of genital HPV DNA positivity with seropositivity was found.In type-specific analysis among females, the presence of antibody against one specific HPV type in sera was associated with the presence of the same HPV type in a cervical specimen  . With stPtrend = 0.017) and higher education levels (Adjusted Ptrend = 0.008) were positively associated with oncogenic HPV positivity (vs. 0–2 partners).Among females, increasing age  . With stThis is the first population-based study to investigate HPV DNA positivity and seropositivity together with correlations between these two HPV markers in both men and women within a single defined test population from rural China. In this study more subjects were simultaneously negative for both HPV DNA and serum antibodies than positive for both HPV DNA and antibodies. Type-specific association of genital HPV infection and HPV seropositivity was observed in women but not in men. The proportion of ever having been infected with HPV differed significantly with gender, sexual behavior and spousal infection status. These data improve our knowledge of the epidemiology and natural history of HPV infection.In this study population, a very small percentage of individuals were positive for both HPV DNA and serum antibodies for any oncogenic HPV . For HPV-16, which was most frequently evaluated previously, the proportion was even smaller , in agreement with most studies591415Despite the rarity of concurrent detection of genital HPV DNA and serum antibodies and weak concordance of these two indices of HPV exposure, we observed that women who were HPV DNA positive were significantly more likely to be seropositive for antibodies against the same HPV type, as compared with HPV DNA negative women. However, no such DNA and antibody type-specific association was found in men. This gender difference may reflect a natural course of infection which is site-specific. Infection in the dry keratinized epithelium of the male genitalia may result less frequently in seroconversion than infection in the soft mucosal surfaces of the cervix171821vs. 65.2%; oncogenic HPV: 34.6% vs. 31.2%; HPV-16: 13.0% vs. 11.9%) in this population. These gender-related disparities in HPV positivity are of uncertain cause. However, much higher genital HPV DNA prevalence  in combination with higher HPV seroprevalence  was observed in males as compared with females of this study population. This together with the fact that men have a lower likelihood of developing an immune response after natural HPV infection27Approximately 2/3 of this study population  was simultaneously negative for oncogenic HPV DNA and antibody, which indicated that there was no evidence for current or past oncogenic HPV infection among this subset of subjects . Data from clinical trials have demonstrated that HPV vaccination would be most effective at protecting against HPV-related cancer among these “unexposed” individuals2325vs. 15.5%, P < 0.001; ≥3 partners: 0.1% vs. 9.2%, P < 0.001). Thus, in addition to potential underreporting of sexual partners, conservative sexual behavior may partly explain the lack of statistical association of HPV positivity and sexual behavior indicators in females. Taken together, sexual practices may play a more important role in HPV exposure among men than among women in rural China.Regarding risk factors, the number of lifetime sexual partners in men was positively associated with oncogenic HPV positivity (DNA positive and/or antibody positive) as expected. However, no such association was found for non-oncogenic HPV, which may be due to insufficient statistical power because of underreporting of sexual partners. We observed that working outside the hometown area and away from the family, which is an indirect indicator of potential increased risk in sexual behaviors30Evaluating spousal concordance for HPV positivity, our results confirmed that in a large population-based sample HPV positivity in one partner increased the risk of type-specific HPV positivity in the other partner, in line with findings of spousal concordance analysis at other levels including HPV DNA level and sero-status level7Several limitations of this study must be noted. First, the nonparticipation and exclusion of beta-globin negative participants may undermine the generalizability of study results. Second, underreporting of risky sexual behaviors resulting from concern about the potential for social stigma may dilute their true effect on HPV positivity. Finally, in order to more accurately assess the prevalence of HPV exposure and the association of HPV DNA positivity and seropositivity, longitudinal data regarding HPV infection and antibody response both in adults and youngsters would be more informative.In summary, the higher proportion of HPV DNA and antibody positivity in men as compared to women, and differing patterns of HPV DNA and antibody association across gender in rural China suggest a site-specific natural course of infection. These findings together with the risk factors and spousal correlations for ever having been infected with HPV provide a basis for further understanding the epidemiological profiles of HPV infection and developing HPV prevention programs.A population-based esophageal cancer cohort study was initiated in rural Anyang, China in 2007–2009As previously described3233Computer-aided interviews were administered in private rooms by interviewers of the same gender as the participant. Information on demographic characteristics, cigarette consumption (defined as at least 1 cigarette per day for 1 year or more), alcohol consumption (defined as use of Chinese liquor at least twice per week for 1 year or more), and characteristics of sexual behavior was collected during these interviews. Information on spouses was also obtained to identify couples among the study subjects, which provided us an opportunity to examine correlation of HPV positivity within couples.DNA was purified on a Biomek 3000 automated workstation using the E.Z.N.A.TM Mag-Bind Tissue DNA Kit . The human β-globin gene was evaluated in all extracted and purified DNA samples. For β-globin positive samples, PCR was used to evaluate for HPV DNA using a highly sensitive primer set (SPF1/GP6+)35353638et al. has been previously described in detail7The expression and preparation of recombinant proteins, and the multiplex serologic assay developed by Waterboer Sera from quadrivalent HPV  vaccine recipients were pooled and included as the positive standard on each plate every day. The inter-plate coefficients of variation (CVs) for HPV-16 L1 across all days ranged from 2.0 to 24.0%, with a median of 15.2%. Reproducibility of measurements for serologic response to HPV-6 and 16 L1 was assessed by randomly selecting 419 sera for blind replicate tests. The correlation coefficients for the MFI values from two assays were 0.78 (HPV-6) and 0.87 (HPV-16).Seropositivity thresholds of MFI levels for each mucosal HPV type  were defined using data from 123 Chinese female students (age 18–24) who reported no history of sexual intercourse. The cut-off was set at three standard deviations above the mean level of MFI reactivity among the remaining samples after an iterative process to exclude positive outliers16Ten HPV types  evaluated for both HPV DNA positivity and seropositivity were included for analysis. A sample was considered positive for any HPV if at least one of these 10 HPV types was detected. Groups of oncogenic  and non-oncogenic types  were classified according to previous reports35Multivariate logistic regression models were used to examine the association of HPV DNA positivity and seropositivity. The primary exposure variable was the presence in the genitalia of HPV infection of a particular type, and the outcome variable was the presence of serum antibody of the same HPV type. Three sets of models were considered: 1) positivity for any HPV type in the list above in this statistical analysis section; 2) positivity for any oncogenic HPV type in the list; 3) positivity for any non-oncogenic HPV type in the list. Because each participant contributed more than one observation (there is one HPV outcome for each HPV type) in each set of models, generalized estimating equations (GEEs) with an exchangeable correlation structure were applied to adjust for possible correlations of different HPV types . To assess the type-specific association of HPV positivity (positive for HPV DNA and/or antibodies) between spouses, the same method of analysis at infection-level was used. The primary exposure variable was the presence of genital HPV DNA or serum antibody of a particular type in the male partner in a couple. The outcome variable was the presence of genital HPV DNA or serum antibody of the same HPV type in his spouse.To identify independent determinants of HPV positivity, variables that were statistically significant in univariate analyses, together with factors previously reported to be potentially associated were entered into multivariate logistic regression models . Trend tests were conducted across ordered groups treating categorical variables as continuous covariates.P values less than 0.05 (two-sided) were considered to be statistically significant.All statistical analysis was performed using Stata for Windows . How to cite this article: Liu, F. et al. Human papillomavirus DNA positivity and seropositivity in rural Chinese men and women: a population-based cross-sectional study. Sci. Rep.6, 26343; doi: 10.1038/srep26343 (2016).