Factors Associated With Recent Decline in Anal Health Among Older Gay and Bisexual Men: A Cross-sectional Analysis.

ABSTRACT: We investigated factors associated with "worse than usual" anal health among gay and bisexual men aged ≥35 years recruited to a longitudinal study of anal human papillomavirus infection/lesions from September 2010 to August 2015.Among 616 participants (median age 49 years; 36% HIV-positive), 42 (6.8%) reported worse than usual anal health in the last 4 weeks. Associated factors included spending less time with gay friends (odds ratio [OR] = 2.25, 95% CI = 1.06-4.77), most time "feeling down"(OR = 9.17, 95% CI = 2.94-28.59), reduced libido (OR = 2.90, 95% CI = 1.52-5.52), current anal symptoms (OR = 6.55, 95% CI = 2.54-16.90), recent anal wart diagnosis (OR = 4.33, 95% CI = 1.98-9.49), and fear of developing anal cancer (OR = 9.34, 95% CI = 4.52-19.28).Concerns regarding anal health should be routinely discussed by clinicians, and potentially associated psychosocial, physical, and sexual issues further explored.

Chlamydia retesting remains low among young women in Australia: an observational study using sentinel surveillance data, 2018-2022.

BACKGROUND: Chlamydia remains the most notified bacterial sexually transmissible infection in Australia with guidelines recommending testing for re-infection at 3months post treatment. This paper aimed to determine chlamydia retesting and repeat positivity rates within 2-4months among young women in Australia, and to evaluate what factors increase or decrease the likelihood of retesting. METHODS: Chlamydia retesting rates among 16-29-year-old women were analysed from Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of sexually transmissible infection and bloodborne virus (ACCESS) sentinel surveillance data (n =62 sites). Among women with at least one positive test between 1 January 2018 and 31 August 2022, retesting counts and proportions within 2-4months were calculated. Logistic regression was performed to assess factors associated with retesting within 2-4months. RESULTS: Among 8758 women who were positive before 31 August 2022 to allow time for follow up, 1423 (16.2%) were retested within 2-4months, of whom 179 (12.6%) tested positive. The odds of retesting within 2-4months were 25% lower if tested in a coronavirus disease 2019 (COVID-9) pandemic year (2020-2022) (aOR=0.75; 95% CI 0.59-0.95). Among 9140 women with a positive test before 30 November 2022, 397 (4.3%) were retested too early (within 7days to 1month) and 81 (20.4%) of those were positive. CONCLUSIONS: Chlamydia retesting rates remain low with around a sixth of women retested within 2-4months in line with guidelines. Re-infection is common with around one in eight retesting positive. An increase in retesting is required to reduce the risk of reproductive complications and onward transmission.

Human papillomavirus and p16INK4a in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis.

We intended to update human papillomavirus (HPV) prevalence and p16INK4a positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction (AF) for oropharyngeal SCC by geographic region. We searched Medline, Embase, and the Cochrane Library to identify published studies of HPV prevalence and p16INK4a positivity alone or together in oropharyngeal SCC before December 28, 2021. Studies that reported type-specific HPV DNA prevalence using broad-spectrum PCR-based testing methods were included. We estimated pooled HPV prevalence, type-specific HPV prevalence, and p16INK4a positivity. AF of HPV was calculated by geographic region. One hundred and thirty-four studies including 12 139 cases were included in our analysis. The pooled HPV prevalence estimate for oropharyngeal SCC was 48.1% (95% confidence interval [CI] 43.2-53.0). HPV prevalence varied significantly by geographic region, and the highest HPV prevalence in oropharyngeal SCC was noted in North America (72.6%, 95% CI 63.8-80.6). Among HPV positive cases, HPV 16 was the most common type with a prevalence of 40.2% (95% CI 35.7-44.7). The pooled p16INK4a positivity in HPV positive and HPV16 positive oropharyngeal SCC cases was 87.2% (95% CI 81.6-91.2) and 91.7% (84.3-97.2). The highest AFs of HPV and HPV16 were noted in North America at 69.6% (95% CI 53.0-91.5) and 63.0% (48.0-82.7). [Correction added on 31 October 2023, after first online publication: the percentage symbol (%) was missing and has been added to 63.0% (48.0-82.7) in the Abstract and Conclusion.] A significant proportion of oropharyngeal SCC was attributable to HPV. HPV16 accounts for the majority of HPV positive oropharyngeal SCC cases. These findings highlight the importance of HPV vaccination in the prevention of a substantial proportion of oropharyngeal SCC cases.

Shared-care models are highly effective and cost-effective for managing chronic hepatitis B in China: reinterpreting the primary care and specialty divide.

Background: We evaluate the impact and cost-effectiveness of shared primary-specialty chronic hepatitis B (CHB) care models in China. Methods: We constructed a decision-tree Markov model to simulate hepatitis B virus (HBV) disease progression in a cohort of 100,000 CHB individuals aged ≥18 years over their lifetime (aged 80). We evaluated the population impacts and cost-effectiveness in three scenarios: (1) status quo; (2) shared-care model with HBV testing and routine CHB follow-ups in primary care and antiviral treatment initiation in specialty care; and (3) shared-care model with HBV testing, treatment initiation and routine CHB follow-up in primary care and treatment for predetermined conditions in specialty care. We evaluated from a healthcare provider's perspective with 3% discounting rate and a willingness-to-pay (WTP) threshold of 1-time China's GDP. Findings: Compared with status quo, scenario 2 would result in an incremental cost of US$5.79-132.43m but a net gain of 328-16,993 quality-adjusted life years (QALYs) and prevention of 39-1935 HBV-related deaths over cohort's lifetime. Scenario 2 was not cost-effective with a WTP of 1-time GDP per capita, but became cost-effective when treatment initiation rate increased to 70%. In contrast, compared with status quo, secnario 3 would save US$144.59-192.93m in investment and achieve a net gain of 23,814-30,476 QALYs and prevention of 3074-3802 HBV-related deaths. Improving HBV antiviral treatment initiation among eligible CHB individuals substantially improved the cost-effectiveness of the shared-care models. Interpretation: Shared-care models with HBV testing, follow up and referring of predetermined conditions to specialty care at an appropriate time, especially antiviral treatment initiation in primary care, are highly effective and cost-effective in China. Funding: National Natural Science Foundation of China.

Cost-effectiveness of artificial intelligence-assisted liquid-based cytology testing for cervical cancer screening in China.

Background: The 2021 World Health Organization (WHO) guidelines for cervical cancer screening recommend human papillomavirus (HPV) DNA or mRNA testing. Artificial intelligence (AI)-assisted liquid-based cytology (LBC) systems also have the potential to facilitate rapid scale-up of cervical cancer screening. We aimed to evaluate the cost-effectiveness of AI-assisted LBC testing, compared with the manual LBC and HPV-DNA testing, for primary cervical cancer screening in China. Methods: We developed a Markov model for a cohort of 100,000 women aged 30 years over a lifetime to simulate the natural history of cervical cancer progression. We evaluated the incremental cost-effectiveness ratios (ICER) of 18 screening strategies (a combination of the three screening methods with six screening frequencies) from a healthcare provider's perspective. The willingness-to-pay threshold (US$30,828) was chosen as three times the Chinese per-capita gross domestic product in 2019. Univariate and probabilistic sensitivity analyses were performed to examine the robustness of the results. Findings: Compared with no screening, all 18 screening strategies were cost-effective, with an ICER of $622-24,482 per quality-adjusted life-year (QALY) gained. If HPV testing after scaling up to population level screening costs $10.80 or more, screening once every 5 years using AI-assisted LBC would be the most cost-effective strategy with an ICER of $8790/QALY gained compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier. Its probability of being cost-effective was higher (55.4%) than other strategies. Sensitivity analyses showed that the most cost-effective strategy would become AI-assisted LBC testing once every 3 years if the sensitivity (74.1%) and specificity (95.6%) of this method were both reduced by ≥10%. The most cost-effective strategy would become HPV-DNA testing once every 5 years if the cost of AI-assisted LBC was more expensive than manual LBC or if the HPV-DNA test cost is slightly reduced (from $10.8 to <$9.4). Interpretation: AI-assisted LBC screening once every 5 years could be more cost-effective than manually-read LBC. Using AI-assisted LBC could have comparable cost-effectiveness to HPV DNA screening, but the relative pricing of HPV DNA testing is critical in this result. Funding: National Natural Science Foundation of China, National Key R&D Program of China.

Performance of Human Papillomavirus Attribution Algorithms to Predict Causative Genotypes in Anal High-Grade Lesions.

BACKGROUND: Gay and bisexual men (GBM) are at increased risk of human papillomavirus (HPV)-associated anal high-grade squamous intraepithelial lesions (HSILs). Understanding the fractions of HSILs attributable to HPV genotypes is important to inform potential impacts of screening and vaccination strategies. However, multiple infections are common, making attribution of causative types difficult. Algorithms developed for predicting HSIL-causative genotype fractions have never been compared with a reference standard in GBM. METHOD: Samples were from the Study of the Prevention of Anal Cancer. Baseline HPV genotypes detected in anal swab samples (160 participants) were compared with HPV genotypes in anal HSILs (222 lesions) determined by laser capture microdissection (LCM). Five algorithms were compared: proportional, hierarchical, maximum, minimum, and maximum likelihood estimation. RESULTS: All algorithms predicted HPV-16 as the most common HSIL-causative genotype, and proportions differed from LCM detection (37.8%) by algorithm (with differences of -6.1%, +20.9%, -20.4%, +2.9%, and +2.2% respectively). Fractions predicted using the proportional method showed a strong positive correlation with LCM, overall (R = 0.73 and P = .002), and by human immunodeficiency virus (HIV) status (HIV positive, R = 0.74 and P = .001; HIV-negative, R = 0.68 and P = .005). CONCLUSIONS: Algorithms produced a range of inaccurate estimates of HSIL attribution, with the proportional algorithm performing best. The high occurrence of multiple HPV infections means that these algorithms may be of limited use in GBM.

Clinical and laboratory aspects of condylomata lata lesions of syphilis.

OBJECTIVES: Condylomata lata are a less common but distinctive syphilitic lesion. Variable theories as to their nature and origin exist. The aim of this study was to determine the clinical and laboratory characteristics of condylomata lata by determining (1): the most closely aligned stage of syphilis, based on the rapid plasma reagin (RPR) titre; (2) symptom duration and (3) Treponema pallidum PCR cycle threshold (CT) values, as an indicator of organism load. METHODS: This was a retrospective study of patients with T. pallidum PCR-positive condylomata lata lesions, attending a clinic in Melbourne, Australia, between 2011 and 2021. Syphilis serology was undertaken and RPR titres compared between condylomata lata, primary and secondary syphilis cases. RESULTS: 51 cases with T. pallidum PCR-positive condylomata lata were included. 41 cases were in men, 40 of whom were men who have sex with men (MSM), and 10 in women. Twelve of 51 (24%) cases were in HIV-positive MSM. Thirty-three of 51 (65%) had other mucocutaneous signs of secondary syphilis; 18 (35%) had no other signs of secondary syphilis. The median RPR titre among the 51 condylomata lata cases was 1:128, compared with the median RPR titre of primary syphilis (1:4) and of secondary syphilis (1:128). The median duration of lesions was 24 (IQR 10-60) days, with no significant difference between those with and without other signs of secondary syphilis (p=0.75). Median CT values for condylomata lata (CT=31) and primary syphilis (CT=31) were significantly lower than for other secondary syphilis lesion types (CT=33), indicating higher T. pallidum loads for condylomata lata and primary lesions compared with other secondary syphilis lesion types. DISCUSSION: These findings support condylomata lata as lesions that occur during the secondary stage of syphilis and which are likely to be highly infectious.

The Urethral Microbiota of Men with and without Idiopathic Urethritis.

Nongonococcal urethritis (NGU) is a common genital tract syndrome in men, and up to 50% of cases are considered idiopathic, i.e., no etiological agent is identified. This poses challenges for clinicians in the diagnosis and treatment of NGU and often results in antibiotic misuse and overuse. Therefore, to identify potential infectious causes of urethritis and inform clinical management of urethritis cases, we characterized and compared the urethral microbiota of men with and without idiopathic urethritis. Participants were derived from a case-control study that examined viral and bacterial pathogens and sexual practices associated with NGU. Men with NGU who tested negative for established causes of NGU (Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenoviruses, herpes simplex virus [HSV]-1, and/or HSV-2) were classified as idiopathic cases, and the controls were men reporting no current urethral symptoms. Men provided a urine sample that was used to characterize the urethral microbiota using 16S rRNA gene sequencing. Bacterial taxa associated with idiopathic urethritis were identified using analysis of compositions of microbiomes with bias correction. When stratified by sex of sexual partner, we found that the abundance of Haemophilus influenzae was significantly increased in men who have sex with men with idiopathic urethritis, and the abundance of Corynebacterium was significantly increased in men who have sex with women with idiopathic urethritis. Other taxa, including Ureaplasma, Staphylococcus haemolyticus, Streptococcus pyogenes, Escherichia, and Streptococcus pneumoniae/pseudopneumoniae, dominated the urethral microbiota of idiopathic urethritis cases but not controls, suggesting that these organisms may also contribute to urethritis. Importantly, the taxa we identified represent biologically plausible causes of urethritis and should be prioritized for future study. IMPORTANCE Nongonococcal urethritis (NGU) is the commonest genital tract syndrome in men and is nearly universally presumptively treated with an antibiotic. Common causes of NGU include Chlamydia trachomatis and Mycoplasma genitalium, but in more than 50% of cases, an infectious cause is not identified. In this case-control study, we found that the urethral microbiota composition differed between men with and without idiopathic urethritis and differed by sex of sexual partner. We identified specific bacterial taxa that were associated with idiopathic urethritis, including Haemophilus influenzae and Corynebacterium. These data, together with the finding that key bacterial taxa were found to dominate the urethral microbiota of cases but not controls, suggest that a range of bacteria contribute to urethritis and that these organisms may be influenced by sexual practices. Through identifying the infectious causes of urethritis, we can inform appropriate targeted diagnostic and treatment practices and importantly reduce misuse and overuse of antibiotics.

"How PrEPared are you?": Knowledge of and attitudes toward PrEP among overseas-born and newly arrived gay, bisexual, and other men who have sex with men in Australia.

Introduction: Overseas-born and newly arrived gay and bisexual men and men who have sex with men (GBMSM) are at higher risk of acquiring HIV in comparison to Australian-born GBMSM. Pre-exposure prophylaxis (PrEP) is subsidized by the Australian government under Medicare, Australia's universal health insurance scheme, however many members of this population are Medicare-ineligible, which could prevent them from accessing PrEP. We wanted to explore participants' knowledge of and attitudes toward PrEP and their opinions of new PrEP modalities, namely injectable PrEP and PrEP implants. Methods: We conducted in-depth qualitative interviews between February 2021 to September 2021 with 22 overseas-born, newly arrived (<5 years in Australia) GBMSM of varying PrEP use. We asked their opinions of PrEP and their preferences of new PrEP modalities. Interviews were audio recorded and transcribed verbatim. We conducted a reflexive thematic analysis to interpret the data. Results: Participants' views reflect the intersections between systemic factors, such as Medicare ineligibility and the high cost of PrEP, with socio-cultural factors, such as lack of knowledge about PrEP, internalized stigma stemming from homo- and sex-negativity, and stigmatizing attitudes toward PrEP and PrEP users. For participants who were on PrEP, being community connected, having a positive relationship with doctors and nurses, and being informed of the option to purchase PrEP from overseas pharmacies at a low cost helped them to overcome some of these barriers. Additionally, there was a strong preference for injectable PrEP but not PrEP implants. Participants stressed the importance of providing a comprehensive information about PrEP specific to this population and to make PrEP free for all. Conclusions: We concluded that resources about PrEP specific to this population that address both systemic and socio-cultural factors are needed, and for these resources to be available in languages other than English. This is to coincide with on-going advocacy to increase the capacity of publicly funded sexual health clinics to provide multilingual PrEP services for people without Medicare, and to make PrEP free for all. These combined strategies have the potential to increase PrEP knowledge and uptake among this population.

Global Pattern and Trends in Penile Cancer Incidence: Population-Based Study.

BACKGROUND: Penile cancer is a relatively rare genital malignancy whose incidence and mortality are rising in many countries. OBJECTIVE: This study aims to assess the recent incidence and mortality patterns and incidence trends of penile cancer. METHODS: The age-standardized incidence and mortality rates (ASIR and ASMR, respectively) of penile cancer in 2020 were estimated from the Global Cancer Registries (GLOBOCAN) database. Incidence trends of penile cancer from 1973 to 2012 were assessed in 44 populations from 43 countries using the Cancer Incidence in Five Continents plus (CI5plus) and the Nordic Cancer Registries (NORDCAN) databases. Average annual percentage change was calculated to quantify trends in ASIR using joinpoint regression. RESULTS: Globally, the estimated ASIR and ASMR of penile cancer were 0.80 (per 100,000) and 0.29 (per 100,000) in 2020, equating to 36,068 new cases and 13,211 deaths in 2020, respectively. There was no significant correlation between the ASIR (P=.05) or ASMR (P=.90) and Human Development Index. In addition, 15 countries saw increasing ASIR for penile cancer, 13 of which were from Europe (United Kingdom, Lithuania, Norway, Estonia, Finland, Sweden, Cyprus, Netherlands, Italy, Croatia, Slovakia, Russia, and the Czech), and 2 from Asia (China and Israel). CONCLUSIONS: Although the developing countries still bear the higher incidence and mortality of penile cancer, the incidence is on the rise in most European countries. To mitigate the disease burden resulting from penile cancer, measures to lower the risk for penile cancers, including improving penile hygiene and male human papillomavirus vaccination, may be warranted.

Comparison of four assays for human papillomavirus detection in the anal canal.

OBJECTIVE: Anal cancer is preceded by high-risk human papillomavirus (HRHPV) infection, predominantly HPV16. No HPV assay is licenced for use in anal screening. We aimed to determine the sensitivity and specificity of four anal canal swab HPV assays to predict high-grade squamous epithelial lesions (HSIL). METHODS: In a cohort of Australian HIV-positive and negative gay and bisexual men, we compared the sensitivity and specificity of detection of 13 anal HRHPV genotypes by Linear Array (LA), Cobas 4800, EuroArray, and Anyplex II HPV28 (+ and ++ cut offs), compared their ability to predict prevalent anal HSIL, and compared anal canal HRHPV detection with HRHPV isolated from HSIL using laser capture microdissection (LCM). RESULTS: A total of 475 participants had baseline results available for all four assays (166, 35.0% HIV positive), and 169 participants had a diagnosis of cytological and/or histological HSIL. The HPV16 and any HRHPV detection were highest with Anyplex II HPV28 (+) (156, 32.8% 95% CI 28.6-37.2 and 359, 75.6%, 95% CI 71.5-79.4, respectively). For detection of concurrent HSIL and HPV16, the assay sensitivity was similar, ranging from 49.1%, 95% CI 41.4-56.9 (Anyplex II HPV28 ++) to 55.0%, 95% CI 47.2-62.7 (Anyplex II HPV28 +). For concurrent HSIL and any HRHPV detection, EuroArray was more specific than Anyplex II HPV28 (+) (45.9% 95% CI 40.2-51.7 vs 36.7%, 95% CI 31.3-42.4, p = 0.021) and had comparable specificity with Anyplex II HPV28 (++) (45.9% vs 47.2%, 95% CI 41.5-53.0, p = 0.75). All assays had high sensitivities for predicting HPV16 detected on LCM (92.5-97.5%). Anyplex II HPV28 and EuroArray were significantly more sensitive than LA for lesions caused by non-HPV16 HRHPV types on LCM. DISCUSSION: Anyplex II HPV28 and EuroArray detected more non-16 HRHPV genotypes than LA. Increasing the Anyplex II HPV28 cutoff improved specificity without compromising sensitivity for detection of concurrent HSIL.

Human papillomavirus vaccine coverage in male-male partnerships attending a sexual health clinic in Melbourne, Australia.

We aimed to investigate the sexual mixing by human papillomavirus (HPV) vaccination status in male-male partnerships and estimate the proportion of male-male partnerships protected against HPV. We analyzed male-male partnerships attending the Melbourne Sexual Health Center between 2018 and 2019. Data on self-reported HPV vaccination status were collected. Newman's assortativity coefficient was used to examine the sexual mixing by HPV vaccination status. Assortativity refers to the tendency of individuals to have partners with similar characteristics (i.e. same vaccination status). Of 321 male-male partnerships where both men reported their HPV vaccination status, 52.6% (95% CI: 47.0-58.2%) partnerships had both men vaccinated, 32.1% (95% CI: 27.0-37.5%) partnerships had only one man vaccinated, and 15.3% (95% CI: 11.5-19.7%) had both men unvaccinated. The assortativity on HPV vaccination status was moderate (assortativity coefficient = 0.265, 95% CI: 0.196-0.335). There were about 15% of male-male partnerships where both men were not protected against HPV. Interventions targeting vaccinated individuals to encourage their unvaccinated partners to be vaccinated might increase the HPV vaccine coverage.

How is cervical cancer screening discussed with clients at a sexual health clinic in Melbourne, Australia?

We conducted a survey among 40 clinicians working at the Melbourne Sexual Health Centre in November 2021. We asked clinicians how they discussed cervical screening with their clients. All clinicians used the term 'Cervical Screening Test (CST)' when discussing cervical cancer screening with clients. However, 19 clinicians (48%) also used the term 'Pap smear', particularly among older women as they were more familiar with Pap smear than CST. Twenty-five (63%) clinicians believed that clients did not understand the difference between Pap smears and CST. Further education is required to improve the understanding between the terminologies.

Using machine learning approaches to predict timely clinic attendance and the uptake of HIV/STI testing post clinic reminder messages.

Timely and regular testing for HIV and sexually transmitted infections (STI) is important for controlling HIV and STI (HIV/STI) among men who have sex with men (MSM). We established multiple machine learning models (e.g., logistic regression, lasso regression, ridge regression, elastic net regression, support vector machine, k-nearest neighbour, naïve bayes, random forest, gradient boosting machine, XGBoost, and multi-layer perceptron) to predict timely (i.e., within 30 days) clinic attendance and HIV/STI testing uptake after receiving a reminder message via short message service (SMS) or email). Our study used 3044 clinic consultations among MSM within 12 months after receiving an email or SMS reminder at the Melbourne Sexual Health Centre between April 11, 2019, and April 30, 2020. About 29.5% [899/3044] were timely clinic attendance post reminder messages, and 84.6% [761/899] had HIV/STI testing. The XGBoost model performed best in predicting timely clinic attendance [mean [SD] AUC 62.8% (3.2%); F1 score 70.8% (1.2%)]. The elastic net regression model performed best in predicting HIV/STI testing within 30 days [AUC 82.7% (6.3%); F1 score 85.3% (1.8%)]. The machine learning approach is helpful in predicting timely clinic attendance and HIV/STI re-testing. Our predictive models could be incorporated into clinic websites to inform sexual health care or follow-up service.

Possible Reactivation of Latent Anal Human Papillomavirus Associated with Markers of Immune Dysfunction in Gay and Bisexual Men.

BACKGROUND: It is unknown whether reactivation of human papillomavirus (HPV) after latency occurs in the anus. We measured incidence and predictors of incident anal HPV in sexually inactive gay and bisexual men (GBM) as a surrogate of HPV reactivation. METHODS: The Study of the Prevention of Anal Cancer collected data on sexual behavior, anal cytology, HPV DNA, histology and HPV serology. HPV incidence during periods when zero sexual partners were reported in the last six months at both the current and previous annual visit ("no sexual activity") was analyzed by Cox regression using the Wei-Lin-Weissfeld method to determine univariable predictors. RESULTS: Of 617 men enrolled, 525 had results for ≥2 visits, of whom 58 (11%) had ≥ one period of "no sexual activity". During sexually inactive periods, there were 29 incident high risk HPV infections in 20 men, which occurred more commonly in older men (Ptrend = 0.010), HIV-positive men (HR = 3.12; 95% CI, 0.91-16.65), longer duration of HIV (Ptrend = 0.028), history of AIDS defining illness (P = 0.010), lower current (P = 0.010) and nadir CD4 count (P = 0.014). For 18 of 29 infections with available results, 12 men remained type-specific HRHPV L1 seronegative. None were consistently seropositive. A new diagnosis of HSIL occurred in only two men, caused by an HPV type other than the incident type. CONCLUSIONS: Our findings suggest that in sexually inactive GBM, anal HRHPV incidence is relatively common, and is associated with increasing age and immune dysfunction, a pattern consistent with HPV reactivation. IMPACT: Reactivation of anal HPV may occur.

The diagnostic accuracy of pooled testing from multiple individuals for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae: a systematic review.

OBJECTIVES: Molecular testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is costly. Therefore, we appraised the evidence regarding pooling samples from multiple individuals to test for CT/NG. METHODS: In this systematic review, we searched 5 databases (2000-2021). Studies were included if they contained primary data describing pooled testing. We calculated the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. RESULTS: We included 22 studies: most were conducted in high-income countries (81.8%, 18 of 22), among women (73.3%, 17 of 22), and pooled urine samples (63.6%, 14 of 22). Eighteen studies provided 25 estimates for the meta-analysis of diagnostic accuracy, with data from 6,913 pooled specimens. The pooled sensitivity for CT was 98.4% (95% confidence intervals [CI]: 96.8-99.2%, I2=77.5, p<0.001), and pooled specificity was 99.9% (95% CI: 99.6-100.0%, I2=62.6, p<0.001). Only 2 studies reported pooled testing for NG, and both reported similarly high sensitivity and specificity as for CT. Sixteen studies provided data on the cost of pooling, reporting cost-savings ranging from 39%-90%. CONCLUSIONS: Pooled testing from multiple individuals for CT is highly sensitive and specific compared with individual testing. This approach has the potential to reduce the cost of screening in populations for which single anatomic site screening is recommended.

Sexual behaviours associated with incident high-risk anal human papillomavirus among gay and bisexual men.

OBJECTIVE: High-risk human papillomavirus (HRHPV) causes anal cancer, which disproportionately affects gay and bisexual men (GBM). We examined sexual behaviours associated with incident anal HRHPV in an observational cohort study of GBM in Sydney, Australia. METHODS: GBM aged 35 years and above were enrolled in the Study of the Prevention of Anal Cancer. Detailed information on sexual practices in the last 6 months, including receptive anal intercourse (RAI) and non-intercourse receptive anal practices, was collected. Anal human papillomavirus (HPV) testing was performed at the baseline and three annual follow-up visits. Risk factors for incident HRHPV were determined by Cox regression using the Wei-Lin-Weissfeld method. RESULTS: Between 2010 and 2015, 617 men were recruited and 525 who had valid HPV results at baseline and at least one follow-up visit were included in the analysis. The median age was 49 years (IQR 43-56) and 188 (35.8%) were HIV-positive. On univariable analysis, incident anal HRHPV was associated with being HIV-positive (p<0.001), having a higher number of recent RAI partners regardless of condom use (p<0.001 for both), preference for the receptive position during anal intercourse (p=0.014) and other non-intercourse receptive anal sexual practices, including rimming, fingering and receptive use of sex toys (p<0.05 for all). In multivariable analyses, being HIV-positive (HR 1.46, 95% CI 1.09 to 1.85, p=0.009) and reporting condom-protected RAI with a higher number of sexual partners (p<0.001) remained significantly associated with incident HRHPV. When stratified by recent RAI, non-intercourse receptive anal practices were not associated with incident HRHPV in men who reported no recent RAI. CONCLUSION: GBM living with HIV and those who reported RAI were at increased of incident anal HRHPV. Given the substantial risk of anal cancer and the difficulty in mitigating the risk of acquiring anal HRHPV, HPV vaccination should be considered among sexually active older GBM. TRIAL REGISTRATION NUMBER: ANZCTR365383.

Intensified partner notification and repeat testing can improve the effectiveness of screening in reducing Chlamydia trachomatis prevalence: a mathematical modelling study.

BACKGROUND: The Australian Chlamydia Control Effectiveness Pilot (ACCEPt) was a cluster randomised controlled trial designed to assess the effectiveness of annual chlamydia testing through general practice in Australia. The trial showed that testing rates increased among sexually active men and women aged 16-29 years, but after 3 years the estimated chlamydia prevalence did not differ between intervention and control communities. We developed a mathematical model to estimate the potential longer-term impact of chlamydia testing on prevalence in the general population. METHODS: We developed an individual-based model to simulate the transmission of Chlamydia trachomatis in a heterosexual population, calibrated to ACCEPt data. A proportion of the modelled population were tested for chlamydia and treated annually at coverage achieved in the control and intervention arms of ACCEPt. We estimated the reduction in chlamydia prevalence achieved by increasing retesting and by treating the partners of infected individuals up to 9 years after introduction of the intervention. RESULTS: Increasing the testing coverage in the general Australian heterosexual population to the level achieved in the ACCEPt intervention arm resulted in reduction in the population-level prevalence of chlamydia from 4.6% to 2.7% in those aged 16-29 years old after 10 years (a relative reduction of 41%). The prevalence reduces to 2.2% if the proportion retested within 4 months of treatment is doubled from the rate achieved in the ACCEPt intervention arm (a relative reduction of 52%), and to 1.9% if the partner treatment rate is increased from 30%, as assumed in the base case, to 50% (a relative reduction of 59%). CONCLUSION: A reduction in C. trachomatis prevalence could be achieved if the level of testing as observed in the ACCEPt intervention arm can be maintained at a population level. More substantial reductions can be achieved with intensified case management comprising retesting of those treated and treatment of partners of infected individuals.

Human Papillomavirus Antibody Levels Following Vaccination or Natural Infection Among Young Men Who Have Sex With Men.

BACKGROUND: Australia introduced a school-based gender-neutral human papillomavirus (HPV) vaccination program for girls and boys aged 12-13 years in 2013. We examined HPV type-specific antibody levels in unvaccinated young men who have sex with men (MSM) with natural infection and compared these with levels in those vaccinated against HPV. METHODS: Serum specimens at baseline were collected from MSM aged 16-20 years in the HYPER1 (Human Papillomavirus in Young People Epidemiological Research) and HYPER2 studies, conducted in 2010-2013 and 2017-2019, respectively. Merck's 4-plex HPV competitive Luminex Immunoassay was used to quantify HPV6-, HPV11-, HPV16-, and HPV18-specific antibodies. We compared antibody levels for each HPV genotype between unvaccinated men (HYPER1) and vaccinated men (HYPER2) using the Mann-Whitney U test. RESULTS: There were 200 unvaccinated men and 127 vaccinated men included in the analysis. Median antibody levels among vaccinated men were significantly higher than levels among unvaccinated men for HPV6 (223 milli-Merck units per milliliter [mMU/mL] vs 48 mMU/mL, P < .0001), HPV11 (163 mMU/mL vs 21 mMU/mL, P < .0001), HPV16 (888 mMU/mL vs 72 mMU/mL, P < .0001), and HPV18 (161 mMU/mL vs 20 mMU/mL, P < .0001). Antibody levels did not change over time for up to 66 months for all 4 genotypes among vaccinated men. CONCLUSIONS: Among young MSM vaccinated with the quadrivalent HPV vaccine, antibody levels for HPV6, HPV11, HPV16, and HPV18 were significantly higher than those in unvaccinated MSM following natural infection. Antibody levels following vaccination appeared to remain stable over time. CLINICAL TRIALS REGISTRATION: NCT01422356 for HYPER1 and NCT03000933 for HYPER2.