Guidelines for Preventive Activities in General Practice

Human papillomaviruses (HPVs) are small double-stranded DNA viruses that infect the cutaneous and mucosal epithelium. Infection by specific HPV types has been linked to the development of cervical carcinoma. HPV infects epithelial cells that undergo terminal differentiation and so encode multiple mechanisms to override the normal regulation of differentiation to produce progeny virions. Two viral proteins, E6 and E7, alter cell cycle control and are the main arbitrators of HPV-induced oncogenesis. Recent data suggest that E6 and E7 also play a major role in the inhibition of the host cell innate immune response to HPV. The E1 and E2 proteins, in combination with various cellular factors, mediate viral replication. In addition, E2 has been implicated in both viral and cellular transcriptional control. Despite decades of research, the function of other viral proteins still remains unclear. While prophylactic vaccines to block genital HPV infection will soon be available, the widespread nature of HPV infection requires greater understanding of both the HPV life cycle as well as the mechanisms underlying HPV-induced carcinogenesis.

Human papillomaviruses: basic mechanisms of pathogenesis and oncogenicity

ContextNon–cytology-based screen-and-treat approaches for cervical cancer prevention have been developed for low-resource settings, but few have directly addressed efficacy.ObjectiveTo determine the safety and efficacy of 2 screen-and-treat approaches for cervical cancer prevention that were designed to be more resource-appropriate than conventional cytology-based screening programs.Design, Setting, and PatientsRandomized clinical trial of 6555 nonpregnant women, aged 35 to 65 years, recruited through community outreach and conducted between June 2000 and December 2002 at ambulatory women’s health clinics in Khayelitsha, South Africa.InterventionsAll patients were screened using human papillomavirus (HPV) DNA testing and visual inspection with acetic acid (VIA). Women were subsequently randomized to 1 of 3 groups: cryotherapy if she had a positive HPV DNA test result; cryotherapy if she had a positive VIA test result; or to delayed evaluation.Main Outcome MeasuresBiopsy-confirmed high-grade cervical cancer precursor lesions and cancer at 6 and 12 months in the HPV DNA and VIA groups compared with the delayed evaluation (control) group; complications after cryotherapy.ResultsThe prevalence of high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) was significantly lower in the 2 screen-and-treat groups at 6 months after randomization than in the delayed evaluation group. At 6 months, CIN 2+ was diagnosed in 0.80% (95% confidence interval [CI], 0.40%-1.20%) of the women in the HPV DNA group and 2.23% (95% CI, 1.57%-2.89%) in the VIA group compared with 3.55% (95% CI, 2.71%-4.39%) in the delayed evaluation group (P<.001 and P = .02 for the HPV DNA and VIA groups, respectively). A subset of women underwent a second colposcopy 12 months after enrollment. At 12 months the cumulative detection of CIN 2+ among women in the HPV DNA group was 1.42% (95% CI, 0.88%-1.97%), 2.91% (95% CI, 2.12%-3.69%) in the VIA group, and 5.41% (95% CI, 4.32%-6.50%) in the delayed evaluation group. Although minor complaints, such as discharge and bleeding, were common after cryotherapy, major complications were rare.ConclusionBoth screen-and-treat approaches are safe and result in a lower prevalence of high-grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and 12 months.Trial Registrationhttp://clinicaltrials.gov Identifier: NCT00233727.

https://jamanetwork.com/journals/jama/articlepdf/201798/JOC50124.pdf

Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial.

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Screen-and-Treat Approaches for Cervical Cancer Prevention in Low-Resource Settings

Cervical cancer is on the declining trend in India according to the population-based registries; yet it continues to be a major public health problem for women in India. Multifactorial causation, potential for prevention, and the sheer threat it poses make cervical cancer an important disease for in-depth studies, as has been attempted by this paper. This paper attempts to review the available knowledge regarding the epidemiology and pattern of cervical cancer; types of HPV (human papilloma virus) prevalent among cervical cancer patients and among women in general, high-risk groups such as commercial sex workers, and HIV (human immunodeficiency virus)-positive women; and the role of the national program on cancer in control efforts. The peak age of incidence of cervical cancer is 55-59 years, and a considerable proportion of women report in the late stages of disease. Specific types of oncogenic HPV-16, 18 have been identified in patients with cervical cancer. Other epidemiological risk factors are early age at marriage, multiple sexual partners, multiple pregnancies, poor genital hygiene, malnutrition, use of oral contraceptives, and lack of awareness. A multipronged approach is necessary which can target areas of high prevalence identified by registries with a combination of behavior change communication exercises and routine early screening with VIA. Sensitizing the people of the area, including menfolk, is necessary to increase uptake levels. Vaccination against types 16 and 18 can also be undertaken after taking into confidence all stakeholders, including the parents of adolescent girls. Preventing and treating cervical cancer and reducing the burden are possible by targeting resources to the areas with high prevalence.

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Epidemiology of cervical cancer with special focus on India

Cervical cancer is caused by infection with a range of high risk oncogenic human papillomavirus (HPV) types, and it is now accepted that >99% of cervical cancer is initiated by HPV infection. The estimated lifetime risk of cervical cancer is nevertheless relatively low (less than I in 20 for most community based studies). Although sensitivity and specificity of the available diagnostic techniques are suboptimal, Screening for persistent HPV infection is effective in reducing the incidence of cervical cancer. Infection can be detected by molecular techniques or by cytological examination of exfoliated cervical cells. Persistent infection is the single best predictor of risk of cervical cancer.(1) The latest findings of HPV and cervical cancer research need to be widely disseminated to the scientific and medical societies that are updating screening and management protocols, public health professionals, and to women and clinicians. This report reviews current evidence, clinical implications and directions for further research in the prevention, control and management of cervical cancer. We report the conclusions of the Experts' Meeting at the EUROGIN 2003 conference. (C) 2003 Wiley-Liss, Inc.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.11530

Torn Wright

Papers

Cervical cancer control, priorities and new directions.