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.
METHODS: Liquid based cervico-vaginal cytology specimens with squamous abnormalities and corresponding histology from 97 women with subsequent colposcopy and biopsy were included. The specimens were then subjected to the dual stain and Roche Cobas 4800 multiplex real time PCR HPV DNA testing. The sensitivity and specificity of the dual stain and HPV testing were calculated using CIN 2+ on histology as a reference standard.
RESULTS: The sensitivity and specificity of the dual stain in detecting histology proven CIN 2+ was 93.7% and 76.5% while HPV testing was 85.7% and 14.7% respectively. Of the 44 women with ASCUS or LSIL on cytology, the dual stain also reduced the number of unnecessary colposcopy referrals from 27 to 7 when used as a triage marker compared to HPV testing.
CONCLUSION: p16/Ki-67 dual stain was more sensitive and specific than HPV testing in determining the presence of CIN 2+ on histology. It could triage low grade cervico-vaginal specimens more effectively and potentially help women avoid unnecessary colposcopies. Future studies are needed to further evaluate its role in cervical cancer screening programmes.
METHODS: In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads.
RESULTS: Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found.
CONCLUSIONS: Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.
METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥ 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7).
CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.