Prevalence of & Risk Factors for Anal Oncogenic Human Papillomavirus Infection among HIV-Infected Women in France in the cART Era

BACKGROUND:

Little is known about the type-specific prevalence of anal human papillomavirus (HPV) infection and risk factors for anal high-risk (HR) HPV infection in HIV-infected women.

METHODS:

A cross-sectional study of anal and cervical HPV infection was nested within a gynaecological cohort of HIV-infected women. Specimens were tested for type-specific DNA using Linear Array.

RESULTS:

The study population consisted of 311 women with a median age of 45.3 years, of whom 42.8% originated from sub-Saharan Africa and 96.8% were receiving combination antiretroviral therapy. The median CD4 cell count was 612/mm³ and HIV load was below 50 copies/mL in 84.1%. HR-HPV types were detected in the anal canal in 148 (47.6%) and in the cervix in 82 (26.4%) women. HPV16 was the most prevalent type in both the anal canal (13.2% of women) and the cervix (5.1%). In multivariable analysis, factors associated with prevalent anal HR-HPV infection were CD4 count below 350/mm³ (OR, 2.9;95%CI:1.3-6.5), concurrent cervical lesions (OR, 2.6;95%CI:1.0-4.3), and cervical HR-HPV infection (OR, 1.8;95%CI: 1.0-3.2).

CONCLUSION:

The high prevalence of high-risk HPV types, including HPV16, in the anal canal of HIV-positive women is concerning. Anal cancer screening should be considered for HIV-positive women as part of their routine care.

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By:   Heard I1, Poizot-Martin I2, Potard V3, Etienney I4, Crenn-Hebert C5, Moore C6, Touraine P7, Cubie H6, Costagliola D8; ANRS-C017 VIHGY Study Group.

• 1French Human papillomavirus Reference Laboratory, Institut Pasteur, Paris, France Department of Endocrinology and Reproductive Medicine, IE3M, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique, Hôpitaux de Paris (AP-HP), Paris, France.
• 2Aix Marseille Univ, Sainte-Marguerite Hospital, Immuno-hematology Clinic Unit, Assistance Publique, Hôpitaux de Marseille, Marseille, France Inserm U912, Marseille, France.
• 3Sorbonne Universités, UPMC Univ Paris 06,INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136) F75013, Paris, France INSERM Transfert, Paris, France.
• 4Proctologie unit, Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France.
• 5Assistance Publique, Hôpitaux de Paris (AP-HP), HUPNVS, Hôpital Mourier, Colombes, France.
• 6Scottish HPV Reference Laboratory, Edinburgh, UK.
• 7Department of Endocrinology and Reproductive Medicine, IE3M, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique, Hôpitaux de Paris (AP-HP), Paris, France.
• 8Sorbonne Universités, UPMC Univ Paris 06,INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136) F75013, Paris, France. 

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Human Papillomavirus (HPV) Prevalence in Nasal and Antrochoanal Polyps and Association with Clinical Data

The pathogenesis of sinonasal polyposis remains unclear, in spite of several investigative approaches. Antrochoanal polyps, a subgroup of sinonasal polyposis along with allergic- and chronic-inflammatory nasal polyps, mostly originate from the maxillary sinus and develop as a unilateral, pedunculated mass towards the nasopharynx. The human papillomavirus (HPV) is discussed as a possible causative and influencing factor in development and progression of sinonasal polyposis. This study aims to elucidate HPV frequency in nasal polyps and antrochoanal polyps.

Genomic DNA from 257 tissue specimens (166 nasal polyps, 39 antrochoanal polyps and 52 nasal turbinates) was subjected to three different established HPV- polymerase chain reaction assays, testing for 37 low- and high-risk HPV. In addition, immunohistochemical analyses for HPV16 were carried out, as well as immunohistochemistry and western blots of p16, a biomarker for HPV induced cancer.

HPV-DNA was detected in 53.8% of antrochoanal polyps, 15.1% of nasal polyps, and 5.8% of nasal turbinates. HPV16 was the predominant type with a detection rate of 76% in nasal polyps and 62% in antrochoanal polyps. Immunohistochemically, HPV positive tissues stained positive for HPV16 antigens and p16 in epithelial cell layers. No significant p16 overexpression was traceable in antrochoanal polyps, nasal polyps and nasal turbinates by western blot. There was no correlation of HPV-status with sex, age, smoking, alcohol consumption or allergic background.

The present study shows a significant frequency of high-risk type HPV16 in antrochoanal polyps. Absence of oncogenic transformation or correlation of the HPV-status with clinical data suggests a latent superinfection, possibly because of anatomical proximity to the oropharynx.

Below:  HPV Immunohistochemistry.

IHC Overview of a representative HPV-positive antrochoanal polyp with HPV16 staining (A). HPV16 E6 protein staining of a representative HPV-positive antrochoanal polyp, relevant epithelial region shown (B) with corresponding negative control (C). HPV16 E6 protein staining of a representative HPV-positive nasal polyp, relevant epithelial region shown and subepithelial stained cells (D) with corresponding negative control (E). Discontinuous epithelial cell clusters stained positive in HPV-positive antrochoanal- and nasal polyps.

Full article at:  http://goo.gl/kU4LVr

By: Mareike Knör,1,* Konstantin Tziridis,1 Abbas Agaimy,2 Johannes Zenk,1 and Olaf Wendler1,*

Margaret McLaughlin-Drubin, Editor

¹Experimental Otorhinolaryngology, ENT-Hospital, Head and Neck Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany

²Department of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany

Brigham and Women's Hospital/Harvard Medical School, UNITED STATES

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: JZ OW. Performed the experiments: MK OW. Analyzed the data: KT AA OW MK. Contributed reagents/materials/analysis tools: JZ OW AA. Wrote the paper: MK OW.

* E-mail: ed.negnalre-ku@reldnew.falo (OW); Email: ed.zniam-nizideminu@reonk.ekieram (MK)

 

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Pre-Vaccination Type-Specific HPV Prevalence in Confirmed Cervical High Grade Lesions in the Māori & Non-Māori Populations in New Zealand

Below:  Age-specific prevalence of oncogenic HPV types by histology grade and ethnicity. Any HR HPV – any high risk (HR) HPV infection, regardless of co-infection with other HPV types; Any HPV 16 - HPV 16 infection, regardless of co-infection with other oncogenic HPV types; Any HPV 16 and/or 18 - HPV 16 and/or 18 infection, regardless of co-infection with other oncogenic HPV types; Other HR HPV alone - other high risk HPV infection without co-infection with HPV 16 and/or 18

In confirmed CIN2/3, the prevalence of any oncogenic HPV, HPV16 and HPV18 was 96 % (95 % CI:91–99 %), 54 % (95 % CI:46–63 %), 11 % (95 % CI:7–18 %) in Māori and 96 % (95 % CI:93–98 %), 54 % (95 % CI:48–60 %), 11 % (95 % CI:7–15 %) in non-Māori women, respectively. Age-specific patterns of infection for HPV16/18 in confirmed CIN2/3 differed between the two groups (P _interaction  = 0.02), with a lower prevalence in younger vs. older Māori women (57 % in 20–29 years vs 75 % in 40–69 years) but a higher prevalence in younger vs. older non-Māori women (70 % in 20–29 years vs 49 % in 40–69 years); the difference in the age-specific patterns of infection for HPV16/18 was not significant either when considering confirmed CIN2 alone (p = 0.09) or CIN3 alone (p = 0.22).

The overall prevalence of vaccine-included types in CIN2/3 was similar in Māori and non-Māori women, implying that the long-term effects of vaccination will be similar in the two groups.

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Direct Benefit of Vaccinating Boys Along with Girls Against Oncogenic Human Papillomavirus: Bayesian Evidence Synthesis

Below:  Burden of HPV associated cancers in men in the Netherlands in relation to vaccine coverage of girls, overall and separately for carcinomas of oropharynx, anus, and penis. White bars (posterior median plus 1 SD) denote QALYs lost to all HPV types, whereas coloured bars denote estimated burden from vaccine preventable HPV types 16 and 18

Results Before HPV vaccination, 14.9 (95% credible interval 12.2 to 18.1) QALYs per thousand men were lost to vaccine preventable cancers associated with HPV in the Netherlands. This burden would be reduced by 37% (28% to 48%) if the vaccine uptake among girls remains at the current level of 60%. To prevent one additional case of cancer among men, 795 boys (660 to 987) would need to be vaccinated; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2162, 3486, and 1975, respectively. The burden of HPV related cancer in men would be reduced by 66% (53% to 805) if vaccine uptake among girls increases to 90%. In that case, 1735 boys (1240 to 2900) would need to be vaccinated to prevent an additional case; with tumour specific numbers for anal, penile, and oropharyngeal cancer of 2593, 29107, and 6484, respectively.

Conclusions Men will benefit indirectly from vaccination of girls but remain at risk of cancers associated with HPV. The incremental benefit of vaccinating boys when vaccine uptake among girls is high is driven by the prevention of anal carcinomas, which underscores the relevance of HPV prevention efforts for men who have sex with men.

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