Background: Human papillomavirus (HPV)-associated anogenital malignancies occur frequently in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). The purpose of our study was to determine if the high frequency of these cancers is due to lifestyle factors associated with both HPV and HIV infections or to immunosuppression following HIV infection. Methods: We studied invasive and in situ HPVassociated cancers among 309 365 U.S. patients with HIV infection/AIDS (257 605 males and 51 760 females) from 5 years before the date of AIDS onset to 5 years after this date. Sex-, race-, and age-standardized ratios of observedto-expected cancers served as measures of relative risk (RR). Trend tests were used to evaluate changes in the RRs during the 10 years spanning AIDS onset. All statistical tests were two-sided. Results: All HPV-associated cancers in AIDS patients occurred in statistically significant excess compared with the expected numbers of cancers. For in situ cancers, overall risks were significantly increased for cervical (RR = 4.6; 95% confidence interval [CI] = 4.3–5.0), vulvar/vaginal (RR = 3.9; 95% CI = 2.0–7.0), anal (in females, RR = 7.8 [95% CI = 0.2–43.6]; in males, RR = 60.1 [95% CI = 49.2– 72.7]), and penile (RR = 6.9; 95% CI = 4.2–10.6) cancers, and RRs increased during the 10 years spanning AIDS onset for carcinomas in situ of the cervix (P for trend <.001), vulva/ vagina (P for trend = .04), and penis (P for trend = .04). For invasive cancers, overall risks were significantly increased for cervical (RR = 5.4; 95% CI = 3.9–7.2), vulvar/vaginal (RR = 5.8; 95% CI = 3.0–10.2), and anal (RR = 6.8; 95% CI = 2.7–14.0) cancers in females and for anal (RR = 37.9; 95% CI = 33.0–43.4), penile (RR = 3.7; 95% CI = 2.0–6.2), tonsillar (RR = 2.6; 95% CI = 1.8–3.8), and conjunctival (RR = 14.6; 95% CI = 5.8–30.0) cancers in males. However, RRs for invasive cancers changed little during the 10 years spanning AIDS onset. Conclusions: HPV-associated malignancies occur at increased rates in persons with HIV/AIDS. Increasing RRs for in situ cancers to and beyond the time of AIDS onset may reflect the gradual loss of control over HPV-infected keratinocytes with advancing immunosuppression. However, the lack of a similar increase for invasive HPVassociated cancers suggests that late-stage cancer invasion is not greatly influenced by immune status. [J Natl Cancer Inst 2000;92:1500–10]

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Human Papillomavirus-Associated Cancers in Patients With Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome

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Solar Ultraviolet Radiation: Global burden of disease from solar ultraviolet radiation

This article discusses ocular surface squamous neoplasia, a spectrum of malignancy that includes intraepithelial dysplasia, carcinoma in situ of the conjunctiva and cornea, and invasive squamous cell carcinoma.

https://www.ophthalmology.theclinics.com/article/S0896-1549(04)00118-X/pdf

Ocular surface squamous neoplasia.

Background WHO's global burden of disease studies, undertaken since 1996, apportion the total global disease burden, measured in disability-adjusted life years (DALYs), to specific diseases and injuries. Recent assessments of the relative burden due to specific environmental risk factors, plus an understanding of the nature of the risk factor, may guide resource allocation in risk factor management. We report here the global disease burden due to ultraviolet radiation (UVR) exposure. Methods A systematic literature review identified nine diseases with sufficient evidence of a causal relationship with UVR exposure and for which the population attributable fraction (PAF) for UVR could be estimated. For cutaneous malignant melanoma and cataract, the PAF was directly applied to disease burdens already calculated by WHO. For seven other diseases, we developed population-level exposure-disease relationships and used these to calculate disease incidence and mortality, and thence disease burden. We also estimated the disease burden from rickets, osteomalacia and osteoporosis that might result if global UVR exposure was reduced to very low levels. Results UVR exposure is a minor contributor to the world's disease burden, causing an estimated annual loss of 1.6 million DALYs; i.e. 0.1% of the total global disease burden. A markedly larger annual disease burden, 3.3 billion DALYs, might result from reduction in global UVR exposure to very low levels. Conclusions Sun protection messages are important to prevent diseases of UVR exposure. However, without high dietary (or supplemental) intake of vitamin D, some sun exposure is essential to avoid diseases of vitamin D insufficiency.

Estimating the global disease burden due to ultraviolet radiation exposure

Aim—To evaluate the clinical features, treatment results, and recurrence rates in patients with either intraepithelial or invasive squamous cell carcinoma of the conjunctiva. Methods—Retrospective analysis of 60 cases (22 conjunctival intraepithelial and 38 invasive squamous cell carcinomas) to determine patterns of clinical presentation, aetiological factors, and treatment results. The mean patient age was 64 years old. 70% of the patients were male. Patients were treated with a variety of therapies, depending on the degree of tumour involvement; most cases were treated with frozen section controlled excision and adjunctive cryotherapy. Modified eye wall resection or enucleation was done for intraocular invasion and exenteration was done for orbital involvement. Results—Red eye (68%) and ocular irritation (57%) were the most common presenting symptoms. 44% of the patients had other eye findings consistent with extensive solar exposure. 20% of the patients had a history of malignant skin tumours. Visceral malignancies developed in 8%. Scleral involvement was present in 14 (37%), intraocular involvement in five (13%), and orbital invasion in four (11%) cases with invasive squamous cell carcinoma. After a mean follow up of 56 months (18‐226 months) the rate of new or recurrent tumours was 4.5% for intraepithelial squamous carcinoma and 5.3% for invasive squamous cell carcinoma. No patient developed metastases or tumour related deaths. Conclusion—Excision with intraoperative control of the surgical margins and adjunctive cryotherapy results in good tumour control rates.

https://bjo.bmj.com/content/bjophthalmol/83/1/98.full.pdf

Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases

AIM--To investigate the association of human immunodeficiency virus (HIV) infection and carcinoma of the conjunctiva in Africa, and the role of human papilloma virus type 16 (HPV-16). METHODS--Patients in Uganda and Malawi presenting to eye clinics with lesions suspicious of carcinoma were studied. Pathological confirmation of eye lesions was sought. HIV testing of patients who were biopsied and, in Uganda, of matched case control subjects was carried out as was testing of a sample of fixed biopsies for HPV-16 by polymerase chain reaction (PCR). The HIV-1 serology, histopathology of conjunctival biopsies (conjunctival intraepithelial neoplasia (CIN), invasive carcinoma, other lesions), and prevalence of HPV-16 infection were determined. RESULTS--Of Ugandan patients, 27/38 (71%) with carcinoma (27 invasive carcinoma, 11, CIN) were HIV positive compared with 12/76 (16%) of controls (odds ratio 13, 95% confidence interval 5-38). The calculated population aetiological fraction of carcinoma associated with HIV was 66%. Of 32 Malawian patients (20 invasive carcinoma, 12 CIN), 25/29 tested (86%) were HIV positive. HPV-16 infection was found in 7/20 (35%) of carcinoma samples, 0/9 pingueculae, and 2/6 conjunctivitis samples. CONCLUSIONS--HIV infection is strongly associated with an apparent increase in the incidence of conjunctival carcinoma in Africa. While ultraviolet light is probably the prime risk factor and HPV-16 is implicated in a proportion of cases, the interactions of ultraviolet light, HIV, HPVs, and other factors are unclear in the pathogenesis of carcinoma. The disease represents another model of multifactorial epithelial carcinogenesis.

https://bjo.bmj.com/content/bjophthalmol/80/6/503.full.pdf

C. Atenyi-Agaba

Papers

Carcinoma of the conjunctiva and HIV infection in Uganda and Malawi.