Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

Impact of Human Papillomavirus Vaccine Against Anal Human Papillomavirus Infection, Anal Intraepithelial Neoplasia, and Recurrence of Anal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.

BACKGROUND: We sought to summarize human papillomavirus (HPV) vaccine efficacy/effectiveness (VE) against anal HPV infection and anal intraepithelial neoplasia (AIN). METHODS: We performed literature review and meta-analysis to estimate VE, stratified by age and analytic population (per-protocol efficacy [PPE] or intention-to-treat [ITT] population in clinical trials, or all participants in real-world studies). RESULTS: We identified 6 clinical trials and 8 real-world studies. In participants vaccinated at age ≤26 years (mainly human immunodeficiency virus [HIV]-negative individuals), significant VE against incident/prevalent anal HPV infection was reported in clinical trials, with a higher estimate in PPE (2 studies with 2390 participants; VE, 84% [95% confidence interval (CI), 77%-90%]; I2 = 0%) than ITT (2 studies with 4885 participants; 55%, 39%-67%; I2 = 46%) populations or in real-world studies (4 studies with 2375 participants; 77%, 40%-91%; I2 = 81%). HPV vaccination at age ≤26 years was associated with significant VE in preventing persistent anal HPV infection and AIN. No significant VE against anal HPV infection or AIN was found in persons vaccinated at age >26 years (mainly people living with HIV). CONCLUSIONS: There is strong evidence for high VE against anal HPV infection and AIN in HIV-negative individuals vaccinated at age ≤26 years. However, the lower impact in ITT than in PPE populations and the lack of significant effect in people living with HIV aged >26 years indicates that vaccines have the higher impact in populations with less sexual exposure to anal HPV.

Age-Specific Prevalence of Anal and Cervical Human Papillomavirus Infection and High-Grade Lesions in 11 177 Women by Human Immunodeficiency Virus Status: A Collaborative Pooled Analysis of 26 Studies.

BACKGROUND: Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. METHODS: We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology. RESULTS: In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+. CONCLUSIONS: Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

Age-specific burden of cervical cancer associated with HIV: A global analysis with a focus on sub-Saharan Africa.

HIV substantially worsens human papillomavirus (HPV) carcinogenicity and contributes to an important population excess of cervical cancer, particularly in sub-Saharan Africa (SSA). We estimated HIV- and age-stratified cervical cancer burden at a country, regional and global level in 2020. Proportions of cervical cancer (a) diagnosed in women living with HIV (WLHIV), and (b) attributable to HIV, were calculated using age-specific estimates of HIV prevalence (UNAIDS) and relative risk. These proportions were validated against empirical data and applied to age-specific cervical cancer incidence (GLOBOCAN 2020). HIV was most important in SSA, where 24.9% of cervical cancers were diagnosed in WLHIV, and 20.4% were attributable to HIV (vs 1.3% and 1.1%, respectively, in the rest of the world). In all world regions, contribution of HIV to cervical cancer was far higher in younger women (as seen also in empirical series). For example, in Southern Africa, where more than half of cervical cancers were diagnosed in WLHIV, the HIV-attributable fraction decreased from 86% in women ≤34 years to only 12% in women ≥55 years. The absolute burden of HIV-attributable cervical cancer (approximately 28 000 cases globally) also shifted toward younger women: in Southern Africa, 63% of 5341 HIV-attributable cervical cancer occurred in women <45 years old, compared to only 17% of 6901 non-HIV-attributable cervical cancer. Improved quantification of cervical cancer burden by age and HIV status can inform cervical cancer prevention efforts in SSA, including prediction of the impact of WLHIV-targeted vs general population approaches to cervical screening, and impact of HIV prevention.

Comparison of detection strategies for screening and confirming congenital cytomegalovirus infection in newborns in a highly seroprevalent population: a mother-child cohort study.

BACKGROUND: Universal screening of congenital cytomegalovirus (cCMV) infection is important for monitoring and intervention during critical stages of speech and language development. This study aimed to explore the optimal detection strategy for cCMV infection screening. METHODS: Serum samples from pregnant women and saliva and urine samples from their newborns were collected for the anti-CMV IgG and CMV DNA PCR tests, respectively. The sensitivity, specificity, and predictive values as well as the likelihood ratios of 12 potential screening strategies for cCMV infection, based on tests for saliva, urine, and their combination, were evaluated. FINDINGS: A total of 6729 pregnant women were enrolled, and the seroprevalence was 98.1%. Among 6350 newborns that were followed up, 49 were defined as having cCMV infection. In the screening test, the CMV DNA positivity rate remained similar from day 0 to day 5, increased slowly from day 6 to day 13, and became high in newborns beyond 13 days of birth. In the confirmatory testing, the positive rates increased significantly beyond day 21. For the 49 newborns with cCMV infection, the proportion of agreement between saliva and urine testing was poor. Upon evaluating alternative screening strategies, using saliva and urine screening with saliva and urine confirmation as the reference strategy, saliva screening with saliva and urine confirmation showed good diagnostic accuracy and feasibility, with sensitivity, specificity, positive predictive and negative predictive values of 85.7%, 100.0%, 100.0% and 99.9%, respectively. INTERPRETATION: In populations with high seroprevalence, saliva screening with saliva and urine confirmation might be an alternative strategy for screening cCMV infections. The suggested timeframes for screening and confirmation are within 13 (ideally 5) and 21 (ideally 13) days of birth, respectively. FUNDING: National Natural Science Foundation of China, National Science and Technology Major Project of China and Merck & Co., Inc., Kenilworth, New Jersey, U.S.A.

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.

BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.

Sequential Acquisition of Human Papillomavirus Infection at Genital and Anal Sites, Liuzhou, China.

Little is known about the risk for acquiring a concordant human papillomavirus (HPV) infection in a genital (or anal) site after an anal (or genital) HPV infection. We collected 3 sets of anogenital specimens at 6-month intervals from 2,309 men and 2,378 women in Liuzhou, China, and tested these specimens for HPV. The risk for sequential anal HPV infection in participants with a previous genital HPV infection was higher than for participants without an infection (hazard ratio [HR] 4.4, 95% CI 3.4-5.8 for women and HR 2.6, 95% CI 1.4-4.6 for men). For sequential genital HPV infection, women with a previous anal infection had a higher risk (HR 1.9, 95% CI 1.2-3.1), but no major difference was found for men (HR 0.7, 95% CI 0.2-1.9). Our study indicates that autoinoculation might play a major role in anogenital HPV transmission, in addition to direct sexual intercourse, especially for anal infection in women.

Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs. 3 doses in young women.

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9-14 years were randomized to receive 2 doses at months 0 and 6 (n=301) or 3 doses at months 0, 1 and 6 (n=304). Girls aged 15-17 years (n=149) and women aged 18-26 years (n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9-17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9-14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

Sex Differences in the Incidence and Clearance of Anogenital Human Papillomavirus Infection in Liuzhou, China: An Observational Cohort Study.

BACKGROUND: Human papillomavirus (HPV) causes anogenital warts and cancers in men and women. However, little is known about sex differences regarding the natural history of anogenital HPV infection. METHODS: Starting in May 2014, an observational cohort study including 2309 men and 2378 women aged 18-55 years was conducted in Liuzhou, China. Samples from anogenital sites were tested for HPV genotypes by multicolor real-time polymerase chain reaction and melting curve analysis biannually for ~1 year. RESULTS: The incidence of oncogenic HPV infection was similar in men and women (10.3 and 11.5/1000 person-months; P = .275), whereas the incidence of HPV-6/11 infection was higher in men than in women (2.0 vs 1.1; P = .018). The incidence of both oncogenic HPV and HPV-6/11 infections was significantly higher in women in the 18- to 25-year age group than in the older age groups (P = .006 and .011, respectively), whereas it did not vary by age among men (P = .552 and .425, respectively). Additionally, men were more likely than women to clear oncogenic infections (101.5 vs 58.6/1000 person-months; P < .001), but no significant difference was found in the clearance of HPV-6/11 by sex (111.7 vs 84.8; P = .266). The median time to clearance of oncogenic type and type 6/11 infections was not age dependent for either sex (all P > .05). CONCLUSIONS: The natural history of oncogenic and nononcogenic HPV infection differs by sex, which implies that sex-specific vaccination strategies should be considered for oncogenic and nononcogenic HPV. CLINICAL TRIALS REGISTRATION: NCT02188004.

Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis.

BACKGROUND: Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer. METHODS: We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL. FINDINGS: Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16·5, 95% CI 14·2-19·2, p<0·0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4·4, 3·7-5·3, p<0·0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14·1, 11·1-17·9, p<0·0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical high-risk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12·9, 95% CI 6·7-24·8, p<0·0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2·3, 1·6-3·4, p<0·0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23·1, 9·4-57·0, p<0·0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3·6, 2·5-5·3, p<0·0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women). INTERPRETATION: HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women. FUNDING: International Agency for Research on Cancer.

Prevalence, Concordance, and Transmission of Human Papillomavirus Infection Among Heterosexual Couples in Liuzhou, China: An Observational Perspective Study.

BACKGROUND: Knowledge of human papillomavirus (HPV) transmission dynamics, which have important public health implications for designing HPV vaccination strategies, is scarce in undeveloped areas. METHODS: From May to July 2014, 390 couples were enrolled from the general population in Liuzhou, China. Exfoliated cells from male penis shaft/glans penis/coronary sulcus (PGC) and perianal/anal canal (PA) sites and from female vaginal, vulvar, and PA sites were collected biannually for 1 year. RESULTS: The HPV type-specific concordance rate between couples was 15.5% (95% confidence interval [CI], 8.5%-25.0%). For anogenital HPV transmission, the male-to-female transmission rate (11.5 [95% CI, 4.3-30.7] per 1000 person-months) was similar to the female-to-male transmission rate (11.3 [95% CI, 5.9-21.7] per 1000 person-months). The concordance rates between male PGC site and female vaginal, vulvar, and PA sites were 20.0%, 21.8%, and 14.9%, respectively, which were significantly higher than expected by chance. Infections transmitted from males to females seemed mainly originated from male genital sites, whereas for female-to-male transmission, the vaginal, vulvar, and PA sites might be all involved. CONCLUSIONS: Among the heterosexual couples with relatively conservative sexual behavior, the anogenital HPV transmission rate for females to males is similar to that of males to females. In addition to the vagina and vulva, the female PA site is also an important reservoir for HPV transmission.

Sex differences in the incidence and clearance of anal human papillomavirus infection among heterosexual men and women in Liuzhou, China: An observational cohort study.

Anal cancer is primarily caused by human papillomavirus (HPV) infection in both men and women. However, little is known about the sex differences in the natural history of anal HPV infection in a heterosexual population. From May 2014 to March 2016, perianal/anal canal (PA) swab samples were collected semiannually from 2,302 heterosexual men and 2,371 heterosexual women aged 18-55 years old in Liuzhou, China. The specimens were genotyped for HPV DNA by polymerase chain reaction. The incidence rate ratio (IRR) and clearance rate ratio (CRR) were used to analyze the sex differences of incidence and clearance by Poisson regression, respectively. The incidences of PA oncogenic HPV in men and women were 3.4 per 1,000 person-months and 8.6 per 1,000 person-months, respectively, with an IRR of 0.39 (95% confidence interval (CI), 0.29-0.54 for men versus women) (p < 0.0001). The CRR of PA oncogenic HPV infection for men versus women was 1.54 (95% CI, 1.17-2.03) (p = 0.0022). At 12 months, 44% (20/45) of HPV 16/18 infections among women remained positive, whereas no (0/7) infections persisted among men (p = 0.0350). Both the higher incidence and slower clearance of anal carcinogenic HPV infection among women may lead to a higher burden of anal cancer among women than among men in a heterosexual population.

An IgM antibody targeting the receptor binding site of influenza B blocks viral infection with great breadth and potency.

Broadly neutralizing antibodies (bnAbs) targeting the receptor binding site (RBS) of hemagglutinin (HA) have potential for developing into powerful anti-influenza agents. Several previously reported influenza B bnAbs are nevertheless unable to neutralize a portion of influenza B virus variants. HA-specific bnAbs with hemagglutination inhibition (HI) activity may possess the ability to block virus entry directly. Polymeric IgM antibodies are expected to more effectively inhibit virus attachment and entry into target cells due to their higher avidity and/or steric hindrance. We therefore hypothesized that certain RBS-targeted IgM antibodies with strong cross-lineage HI activity might display broader and more potent antiviral activity against rapidly evolving influenza B viruses. Methods: In this study, we generated IgM and IgG bnAbs targeting the RBS of influenza B virus using the murine hybridoma technique. IgM and IgG versions of the same antibodies were then developed by isotype switching and characterized in subsequent in vitro and in vivo experiments. Results: Two IgM and two IgG bnAbs against influenza B virus HA were identified. Of these, one IgM subtype antibody, C7G6-IgM, showed strong HI and neutralization activities against all 20 representative influenza B strains tested, with higher potency and broader breadth of anti-influenza activity in vitro than the IgG subtype variant of itself, or other previously-reported influenza B bnAbs. Furthermore, C7G6-IgM conferred excellent cross-protection against distinct lineages of influenza B viruses in mice and ferrets, performing better than the anti-influenza drug oseltamivir, and showed an additive antiviral effect when administered in combination with oseltamivir. Mechanistically, C7G6-IgM potently inhibits infection with influenza B virus strains from different lineages by blocking viral entry. Conclusion: In summary, our study highlights the potential of IgM subtype antibodies in combatting pathogenic microbes. Moreover, C7G6-IgM is a promising candidate for the development of prophylactics or therapeutics against influenza B infection.

Cytomegalovirus Shedding in Healthy Seropositive Female College Students: A 6-Month Longitudinal Study.

Background: Cytomegalovirus (CMV) establishes a lifelong latent infection after primary infection and may reactivate periodically, with the shedding of infectious virus in body fluids. To better understand the prevalence and shedding model of CMV in immunocompetent seropositive women of childbearing age, a 6-month longitudinal study was conducted in healthy female college students. Methods: A total of 102 nonpregnant female college students aged 18-30 years were enrolled and followed up every 2 weeks for 6 months. Saliva and urine samples were collected at each visit. Serum samples were collected at the first and last visits. Results: All participants were positive for anti-CMV immunoglobulin G (IgG) at entry. During the 6-month period, 29.4% of participants (30 of 102) shed CMV intermittently in saliva or urine. At each visit, the CMV shedding prevalence varied from 2.0% to 10.4% and presented only in 1 bodily fluid. The viral load was low and did not induce marked antibody increases. The baseline anti-CMV IgG level was not found to be associated with viral shedding. Conclusions: CMV shedding in saliva and urine is common and intermittent and does not stimulate an anamnestic antibody response in seropositive immunocompetent women of childbearing age with a low risk of exposure to exogenous infectious sources.

The prevalence and concordance of human papillomavirus infection in different anogenital sites among men and women in Liuzhou, China: A population-based study.

Human papillomavirus (HPV) infection is the pathogenesis of anogenital cancers and genital warts in both men and women, whereas there is a scarcity of large studies focused on HPV prevalence in different anogenital sites of both sexes in the same population. From May to July 2014, 2,309 men and 2,378 women aged 18-55 were enrolled from communities in Liuzhou, China. Penis/glans penis/coronary sulcus (PGC) and perianal/anal canal (PA) specimens of men, and vaginal (VA), vulvar (VU) and PA specimens of women, were collected and genotyped for HPV. The prevalence of any HPV tested in PGC and PA samples from men and VA, VU and PA samples from women was 10.8%, 3.8%, 14.2%, 13.3% and 8.4%, respectively. The concordance of VA and VU was highest (kappa = 0.74), followed by VU and PA (0.44), VA and PA (0.38) and PGC and PA (0.14). Besides sex behavior, ever having used a towel supplied by a hotel was a risk factor for both external genital and PA HPV infection. Our data indicated that women were more of a major reservoir for oncogenic HPV infection of both genital sites and PA sites than was men. In both sexes, the genital sites were more likely than PA sites to harbor HPV infection. The concordance rates of HPV infection between genital sites and PA infection were poor.

Incidence of anogenital warts in Liuzhou, south China: a comparison of data from a prospective study and from the national surveillance system.

To determine the incidence of anogenital warts (AGWs) in the Chinese general population, we compared the data from a prospective study and from the National Notifiable Disease Report System (NNDRS). A cohort study including 2378 women and 2309 men aged 18-55 years old enrolled from Liuzhou, China, was conducted with three scheduled visits at 6-month intervals from May 2014 to March 2016. And, a questionnaire survey was performed to collect the diagnosis history of AGWs at the enrollment visit. The data on reported AGW cases of Liuzhou in the NNDRS from 2006 to 2015 were also analyzed. Overall, the incidence rates of AGWs in the prospective study, in the self-reported diagnosis during past 12 months and in the NNDRS were 1.26 per 1000 person-years (95% confidence interval (CI): 0.16-2.37), 2.35 (95% CI: 1.17-4.20) and 0.183 (95% CI: 0.178-0.187), respectively. Human papillomavirus 6 or 11 were found in all the AGW biopsy samples (10/10). The onset time of AGWs in women was earlier, and the cumulative risk increased more quickly at a young age along with each subsequent younger birth cohort (P<0.0001), whereas slight differences were observed in the different male birth cohorts (P=0.0785). The sexual behavior of individuals and their sexual partners had a strong relationship with self-reported AGWs. Our study indicates that the incidence of AGWs in China is as high as that in developed countries, and the data based on the national surveillance system seriously underestimate the real disease burden of AGWs.

Human papillomavirus prevalence and associated factors in women and men in south China: a population-based study.

Oncogenic human papillomavirus (HPV) infection is a cause of many anogenital cancers in women and men; however, there is little research on HPV prevalence and risk factors that includes both women and men from the same population. A total of 4687 participants, including 2378 women and 2309 men aged 18-55 years old from the same community, were enrolled in the study in Liuzhou, China. Exfoliated cells were collected from the participants from different anatomic sites and were tested for 13 oncogenic and 3 non-oncogenic HPV types. The prevalence of any oncogenic HPV type was higher in women than in men (18.7% vs 9.4%, P<0.001), whereas the prevalence of HPV 6 and 11 infection was similar (1.4% vs 1.2%, P=0.6832). HPV 52, 58, 16, 39 and 18 were the five most prevalent types in both sexes. Sexual and hygienic behaviors were associated with HPV infection in both women and men. We found that oncogenic HPV DNA detection is more prevalent in women than in men in China, whereas the prevalence of HPV 6 and 11 is similar in both sexes. The data indicate that the interaction of host and virus might be different among high- and low-risk HPV types.

[Detection of neutralizing antibodies and DNA of human papillomavirus 16, 18 in women aged 18-45 years in Funing, Jiangsu province].

OBJECTIVE: To understand the distributions of DNA and neutralizing antibodies of human papillomavirus (HPV)16, 18 in 18-45 year-old women. METHODS: Totally, 1494 women were enrolled through multistage random sampling in Funing, Jiangsu province. Cervical exfoliated cells were collected from them for HPV DNA testing, and serum samples were taken from them for the detection of HPV16, 18 neutralizing antibodies by using pseudovirion-based neutralization assay(PBNA). RESULTS: Among the 1494 women, 28(1.9%) and 188(12.6%) were positive for DNA and neutralizing antibody of HPV16 respectively, and 15(1.0%) and 60(4.0%) were positive for DNA and neutralizing antibody of HPV18, respectively. There were no significant differences in the detection rates of DNA and neutralizing antibody of HPV16, 18 among different age groups. About 16.7% of the women were infected with HPV16, 18, or both. CONCLUSION: In Funing county of Jiangsu province, most women aged 18-45 years has no immunity to HPV16 and 18, indicating that they are appropriate targets for HPV 16/18 vaccination.