Reproductive & Genital Health & Risk of Cervical Human Papillomavirus Infection: Results from the Ludwig-Mcgill Cohort Study

Background

There are inconsistencies in the literature on reproductive and genital health determinants of human papillomavirus (HPV) infection, the primary cause of cervical cancer. We examined these factors in the Ludwig-McGill Cohort Study, a longitudinal, repeated-measurements investigation on the natural history of HPV infection.

Methods

We analyzed a cohort subset of 1867 women with one complete year of follow-up. We calculated odds ratios (OR) and 95 % confidence intervals (CI) for reproductive and genital health characteristics from questionnaire and laboratory data in relation to 1-year period prevalence of HPV infection. Two outcomes were measured; the first based on phylogenetic grouping of HPV types based on tissue tropism and oncogenicity (Alphapapillomavirus Subgenus 1: species 1, 8, 10 and 13; Subgenus 2: species 5, 6, 7, 9, 11; Subgenus 3: species 3, 4 and 14) and the second based on transient or persistent HPV infections.

Results

Lifetime (Subgenus 3 OR = 2.00, CI: 1.23–3.24) and current (Subgenus 3 OR = 2.00, CI: 1.15–3.47) condom use and use of contraceptive injections (Subgenus 1 OR = 1.96, CI: 1.22–3.16, Subgenus 2 OR = 1.34, CI: 1.00–1.79) were associated with increased risk of HPV infection. Intrauterine device use was protective (Subgenus 1 OR = 0.48, CI: 0.30–0.75, Subgenus 2 OR = 0.78, CI: 0.62–0.98). These factors were not associated with persistence of HPV infection. Tampon use, previous gynecologic infections and cervical inflammation were associated with an overall increased risk of HPV infection.

Conclusions

Cervical HPV infection was associated with reproductive and genital health factors. Further studies are necessary to confirm the low to moderate associations observed.

Associations between reproductive health and vaginal hygiene factors and the 1-year period prevalence of HPV infection by phylogenetic group in the Ludwig-McGill cohort study

Variable	Subgenus 1a (n = 108)		Subgenus 2a (n = 495)		Subgenus 3a (n = 131)
	ORb	95 % CI	ORb	95 % CI	ORb	95 % CI
Reproductive Health Factors
Condom Use
Former vs. Never	1.28	0.79, 2.07	0.90	0.71, 1.15	2.00	1.23, 3.24
Current vs. Never	1.43	0.83, 2.48	1.09	0.82, 1.45	2.00	1.15, 3.47
Oral Contraceptives
< 6 years vs. Never	1.25	0.66, 1.38	0.98	0.71, 1.35	1.40	0.83, 2.37
6+ years vs. Never	1.23	0.60, 2.53	1.00	0.70, 1.43	0.62	0.32, 1.19
Intrauterine Device
Yes vs. No	0.48	0.30, 0.75	0.78	0.62, 0.98	0.73	0.49, 1.08
Tubal Sterilization
Yes vs. No	1.24	0.65, 1.36	0.84	0.59, 1.21	0.65	0.33, 1.30
Contraceptive Injection
Yes vs. No	1.96	1.22, 3.16	1.34	1.00, 1.79	1.34	0.83, 2.17
Natural Products
Yes vs. No	-	-	0.37	0.13, 1.05	0.74	0.17, 3.20
Vaginal Products
Yes vs. No	-	-	0.82	0.37, 1.81	0.32	0.04, 2.40
Genital Health and Hygiene Factors
Menstrual Cloth
Yes vs. No	0.54	0.32, 0.91	0.93	0.74, 1.18	1.02	0.68, 1.53
Hygienic Tampon
Yes vs. No	1.49	0.87, 2.54	1.33	0.98, 1.81	1.30	0.79, 2.14
Douching
Frequent vs. Infrequent	1.20	0.53, 2.69	1.29	0.83, 2.00	0.11	0.02, 0.81
Douching Products
Natural vs. None	0.96	0.60, 1.54	0.92	0.72, 1.17	0.90	0.57, 1.41
Medical vs. None	1.09	0.23, 5.15	0.97	0.46, 2.06	2.75	0.98, 7.73
Unknown vs. None	1.18	0.27, 5.22	0.51	0.21, 1.21	2.92	1.20, 7.12
Genital Discomfort
Yes vs. No	0.96	0.64, 1.45	0.96	0.78, 1.20	0.89	0.60, 1.31
Recent Discomfort
Yes vs. No	0.99	0.65, 1.50	1.11	0.89, 1.38	1.22	0.84, 1.75
Pain or Bleeding
Yes vs. No	2.83	0.59, 13.51	1.14	0.34, 3.75	0.91	0.12, 7.00
Gynecologic Products
Antibiotic
Former vs. Never	3.86	0.86, 17.34	0.83	0.51, 1.33	1.43	0.52, 3.97
Current vs. Never	5.95	1.14, 30.97	0.97	0.53, 1.79	1.84	0.56, 6.02
Antifungal
Former vs. Never	5.14	1.17, 22.52	1.10	0.70, 1.75	1.85	0.68, 5.02
Current vs. Never	1.64	0.22, 12.24	1.06	0.56, 2.02	1.74	0.49, 6.11
Abrasion
Former vs. Never	-	-	1.68	0.40, 7.72	-	-
Current vs. Never	-	-	1.10	0.08, 16.23	-	-
External Products
Former vs. Never	0.75	0.20, 2.84	-	-	-	-
Current vs. Never	1.36	0.48, 3.89	-	-	-	-
Unknown Products
Former vs. Never	2.82	0.64, 12.42	0.96	0.62, 1.49	2.21	0.81, 6.01
Current vs. Never	3.44	0.63, 18.68	1.10	0.60, 2.03	2.82	0.83, 9.53
Home-made Products
Natural vs. None	1.22	0.78, 1.92	0.91	0.72, 1.15	0.98	0.66, 1.47
Medical vs. None	0.80	0.27, 2.40	1.26	0.77, 2.04	0.76	0.29, 2.02
Unknown vs. None	2.75	0.53, 14.15	1.33	0.45, 3.91	5.33	1.80, 15.82
Vaginal Health Characteristics
Cervical Ectropion
Yes vs. No	0.37	0.05, 2.77	0.89	0.42, 1.91	0.74	0.17, 3.10
Gynecologic Surgery
Yes vs. No	2.05	1.11, 3.79	0.90	0.60, 1.37	0.89	0.42, 1.89
Gynecologic Treatment/Infection
Yes vs. No	1.73	1.13, 2.65	1.17	0.92, 1.50	1.26	0.83, 1.89
Previous Gynecologic Infection
HPV vs. None	3.87	2.09, 7.14	2.02	1.27, 3.19	1.21	0.54, 2.71
Non-HPV vs. None	1.33	0.81, 2.19	1.03	0.78, 1.34	1.27	0.82, 1.97
Cytology Observations
Bacterial Infection
Yes vs. No	1.28	0.63, 2.63	1.30	0.88, 1.91	1.31	0.68, 2.52
Fungal Infection
Yes vs. No	1.25	0.61, 2.54	1.29	0.88, 1.87	1.48	0.83, 2.66
General Inflammation
Yes vs. No	2.10	1.37, 3.22	1.53	1.21, 1.94	1.12	0.74, 1.69

a Subgenus 1 (HPVs-6, 11, 32, 40, 42, 44, 54 and 55), Subgenus 2 (HPVs-16, 18, 26 31, 33–35, 39, 45, 51–53, 56, 58, 59, 66–70, 73 and 82) and Subgenus 3 (HPVs-57, 61, 62, 71, 72, 81, 83, 84 and 89) infections were determined based on the phylogenetic classification of HPV types

b Odds ratios were adjusted for age, lifetime number of sexual partners and empirical confounders (identified using a 5 % change in estimate strategy) such as race, marital status, education, age at first intercourse, age at menarche, number of pregnancies, smoking, alcohol drinking and years since last Pap smear

Full article at:   http://goo.gl/bWRJrg

By:  Eileen Shaw, Agnihotram V. Ramanakumar, Mariam El-Zein, Flavia R. Silva, Lenice Galan, Maria L. Baggio, Luisa L. Villa, Eduardo L. Franco, and for the Ludwig-McGill Cohort Study

Division of Cancer Epidemiology, Department of Oncology, McGill University, Montreal, Canada

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, 546 Pine Avenue West, Montreal, QC H2W 1S6 Canada

Ludwig Institute for Cancer Research, São Paulo, Brazil

Molecular Biology Laboratory, Centre of Translational Oncology, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil

BMC Infect Dis. 2016; 16: 116. Published online 2016 Mar 8. doi:  10.1186/s12879-016-1446-x

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A Randomized Trial of Human Papillomavirus Self-Sampling as an Intervention to Promote Cervical Cancer Screening among Women with HIV

OBJECTIVE:

Women living with HIV experience higher risk of cervical cancer, but screening rates in the United States are lower than recommended. The purpose of this study was to examine whether an intervention using self-sampling of cervicovaginal cells for human papillomavirus (HPV) with results counseling would increase cervical cytology ("Pap") testing among women with HIV.

MATERIALS AND METHODS:

This was a randomized controlled trial to test the effectiveness of an intervention of self-sampling for HPV and results counseling. Participants were 94 women older than 18 years, with HIV infection, attending an HIV clinic for a primary care visit, whose last cervical cancer screening was 18 months or more before baseline. Women were assigned to the intervention or information-only group. The primary outcome was completion of cervical cytology testing within 6 months of baseline. The secondary outcome was the women's perceived threat of developing cervical cancer.

RESULTS:

A total of 94 women were enrolled and analyzed in the study. The cytology completion rate overall was 35% by 6 months from baseline. There were no differences in comparing HPV-positive with HPV-negative women nor comparing them with the information-only group. In the intervention group, a positive HPV test increased perceived threat of cervical cancer.

CONCLUSIONS:

The intervention did not improve cytology test attendance, although education about HPV and cervical cancer risk as part of study procedures was associated with testing for 35% of this group of women whose previous cytology occurred an average of 3.6 years before the baseline appointment. Self-sampling for HPV testing was feasible.

Purchase full article at:   http://goo.gl/wwMV0l

By:  Murphy J1, Mark H, Anderson J, Farley J, Allen J.

• 1Department of Gynecology and Obstetrics, Johns Hopkins University School of Nursing and 
• 2Johns Hopkins School of Medicine, Baltimore, MD.
• J Low Genit Tract Dis. 2016 Apr;20(2):139-44. doi: 10.1097/LGT.0000000000000195. 

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Abnormal Anal Cytology Risk in Women with Known Genital Squamous Intraepithelial Lesion

The purpose of this study was to assess the risk of abnormal anal cytology in women with known genital squamous intraepithelial lesion (SIL). 

This study evaluated 200 women with and without genital SIL who were recruited for anal Pap smears. Women who had abnormal results on equally or over atypical squamous cells of undetermined significance were classified as having abnormal anal cytology. A multiple logistic regression analysis (stepwise) was performed to identify the risk for developing abnormal anal cytology. 

Data were analyzed using the SPSS 20.0 program. The average age was 41.09 (±12.64). Of the total participants, 75.5% did not practice anal sex, 91% did not have HPV-infected partners, 92% did not have any anal pathology, and 68.5% did not have anal bleeding. More than half (57.5%) had genital SIL and a significant number developed abnormal anal cytology: 13% in the total sample and 17.4% in women with genital SIL. A significant association was observed between genital SIL and anal SIL (PR=2.46; p=0.03). In the logistic regression model, women having genital intraepithelial lesion were more likely to have abnormal anal Pap smear (aPR=2.81; p=0.02). 

This report shows that women with genital SIL must be more closely screened for anal cancer.

Below:  Normal (left) and atypical squamous cells of undetermined significance in anal cytology (right)

Full article at:   http://goo.gl/QsiG6F

By:  do Socorro Nobre M1, Jacyntho CM2, Eleutério J Jr3, Gonçalves AK4.

• 1Health Post Graduation Program, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
• 2Department of Obstetric and Gynecology, Faculdade de Medicina Souza Marques, Rio de Janeiro, RJ, Brazil.
• 3Department of Obstetrics and Gynecology, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
• 4Health Post Graduation Program, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Department of Obstetric and Gynecology, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil. Electronic address: anakatherine@ufrnet.br.
• Braz J Infect Dis. 2016 Mar 29. pii: S1413-8670(16)30041-1. doi: 10.1016/j.bjid.2016.01.008. 

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Significant Reduction in the Incidence of Genital Warts in Young Men 5 Years Into the Danish Human Papillomavirus Vaccination Program for Girls and Women

BACKGROUND:

Denmark introduced the quadrivalent human papillomavirus vaccine into the vaccination program for 12- to 15-year-old girls in 2008 to 2009. In 2012, the program was supplemented with a catch-up program for women aged up to 27 years. We evaluated the effectiveness of the Danish vaccination program on the nationwide incidence of genital warts (GWs), after the second catch-up by including information on both hospital treatments and on self-administered treatment with podophyllotoxin. Genital wart incidence was investigated in both sexes; however, the main focus was on potential herd protection of men.

METHODS:

Incident cases of GWs were identified from the Danish National Patient Register and through redemptions of prescription for podophyllotoxin in the Danish National Prescription Registry in 2006 to 2013. Age-specific incidence rates (IRs) were assessed, and estimated annual percentage change (EAPC) was calculated by Poisson regression.

RESULTS:

Genital wart incidence was either stable or increased in both sexes in 2006 to 2008. After introduction of the vaccination program, GW incidence decreased significantly in women aged 12 to 35 years and men aged 12 to 29 years, with rapid decrease among 16- to 17-year-olds (IRwomen, from 1071 to 58 per 100,000 person-years [EAPC, -55.1%; 95% confidence interval, -58.7 to-51.2]; IRmen, from 365 to 77 per 100,000 person-years [EAPC, -36.6%; 95% confidence interval, -40.5 to -32.5] in 2008-2013).

CONCLUSIONS:

We found a significantly decreasing incidence of GWs in women up to 35 years of age after the start of the human papillomavirus vaccination program. A similar pattern was observed for men aged 12 to 29 years, indicating substantial herd protection.

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By:  Bollerup S1, Baldur-Felskov B, Blomberg M, Baandrup L, Dehlendorff C, Kjaer SK.

• 1From the *Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark; †Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Copenhagen, Denmark; and ‡Department of Gynecology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
• Sex Transm Dis. 2016 Apr;43(4):238-42. doi: 10.1097/OLQ.0000000000000418. 

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Prevalence of Anal High-Risk Human Papillomavirus Infections among HIV-Positive and HIV-Negative Men Who Have Sex with Men in Nigeria

BACKGROUND:

Prevalence estimates of anal high-risk human papillomavirus (HR-HPV) are needed in sub-Saharan Africa where HIV is endemic. This study evaluated anal HR-HPV in Nigeria among HIV-positive and HIV-negative men who have sex with men (MSM) for future immunization recommendations.

METHODS:

We conducted a cross-sectional study to compare the prevalence of anal HR-HPV infections between 64 HIV-negative and 90 HIV-positive MSM. Multivariate Poisson regression analyses were used to examine demographic and behavioral risk factors associated with any HR-HPV infections.

RESULTS:

The median age of the 154 participants was 25 years (interquartile range, 22-28 years; range, 16-38 years), and the median age at initiation of anal sex with another man was 16 years (interquartile range, 13-18 years; range, 7-29 years). The prevalence of anal HR-HPV was higher among HIV-positive than HIV-negative MSM (91.1% vs. 40.6%, P < 0.001). In the multivariate analysis, HIV infection (adjusted prevalence ratio [aPR], 2.02; 95% confidence interval [CI], 1.49-2.72), 10 years or more since anal sexual debut (aPR, 1.26; 95% CI, 1.07-1.49), and concurrent relationships with men (aPR, 1.32; 95% CI, 1.04-1.67) were associated with increased anal HR-HPV prevalence.

CONCLUSIONS:

Anal HR-HPV infection is high for young Nigerian MSM, and rates are amplified in those coinfected with HIV. Providing universal coverage as well as catch-up immunization for young MSM may be an effective anal cancer prevention strategy in Nigeria.

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By:  Nowak RG1, Gravitt PE, He X, Ketende S, Dauda W, Omuh H, Blattner WA, Charurat ME; TRUST Study Group.

• 1From the *Institute of Human Virology and †Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD; ‡University of New Mexico Health Sciences Center, Albuquerque, NM; §University of Maryland School of Public Health, College Park, MD; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; and ∥Institute of Human Virology Nigeria, Federal Capital Territory, Nigeria. 
• Sex Transm Dis. 2016 Apr;43(4):243-8. doi: 10.1097/OLQ.0000000000000431.

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