The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.

https://jcp.bmj.com/content/jclinpath/55/4/244.full.pdf

The causal relation between human papillomavirus and cervical cancer

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673607614160.pdf

Human papillomavirus and cervical cancer

BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.

/pdf/quadrivalent-vaccine-against-human-papillomavirus-to-prevent-bjulb1tioi.pdf

Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions

Critical care in pregnancy is a field that remains unevenly researched. Although there is a body of evidence to guide many recommendations in critical care, limited research specifically addresses obstetric critical care. The purpose of this document is to review the available evidence, propose strategies for care, and highlight the need for additional research. Much of the review will, of necessity, focus on general principles of critical care, extrapolating where possible to obstetric critical care.

/pdf/acog-practice-bulletin-2e7yp8vork.pdf

Acog practice bulletin

Incidence data on human papillomavirus (HPV) infection are limited, and risk factors for transmission are largely unknown. The authors followed 603 female university students in Washington State at 4-month intervals between 1990 and 2000. At each visit, a sexual and health questionnaire was completed and cervical and vulvovaginal samples were collected to detect HPV DNA. At 24 months, the cumulative incidence of first-time infection was 32.3% (95% confidence interval: 28.0, 37.1). Incidences calculated from time of new-partner acquisition were comparable for enrolled virgins and nonvirgins. Smoking, oral contraceptive use, and report of a new male sex partner--in particular, one known for less than 8 months before sex occurred or one reporting other partners--were predictive of incident infection. Always using male condoms with a new partner was not protective. Infection in virgins was rare, but any type of nonpenetrative sexual contact was associated with an increased risk. Detection of oral HPV was rare and was not associated with oral-penile contact. The data show that the incidence of HPV associated with acquisition of a new sex partner is high and that nonpenetrative sexual contact is a plausible route of transmission in virgins.

Genital Human Papillomavirus Infection: Incidence and Risk Factors in a Cohort of Female University Students

Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study

Objective: To report the detection rate of interval cancers in women screened by the NHS breast screening programme. Design: Detection of interval cancers by computer linkage of records held by the screening centres in the North Western Regional Health Authority with breast cancer registrations at the regional cancer registry. Setting: North Western Regional Health Authority. Subjects: 137421 women screened between 1 March 1988 and 31 March 1992 who had a negative screening result. Results: 297 invasive interval cancers were detected. The rate of detection of interval cancers expressed as a proportion of the underlying incidence was 31% in the first 12 months after screening, 52% between 12 and 24 months, and 82% between 24 and 36 months. Conclusion: The incidence of interval cancers in the third year after breast screening approaches that which would have been expected in the absence of screening and suggests that the three year interval between screens is too long. Key messages Key messages The NHS breast screening programme invites all women aged 50–64 to be screened every three years To be successful, the incidence of cancers presenting with symptoms between screening appointments—that is, interval cancers—must be kept low More interval cancers than predicted are occurring, and after 24 months the incidence approaches that expected in the absence of screening To reduce the incidence of interval cancers it may be necessary to shorten the screening interval

/pdf/is-the-three-year-breast-screening-interval-too-long-1g5op8ul78.pdf

Is the three year breast screening interval too long? Occurrence of interval cancers in NHS breast screening programme's north western region

Background

Reporting of a recent international comparison of cancer survival rates has left an impression of inadequate treatment of patients in the UK but failed to address adequately the extent to which differences in survival may reflect variation in the completeness and accuracy of cancer registration. The aim of this study was to quantify the extent to which differences in registration practice may confound comparisons of survival from cancer of the colon.



Methods

A cohort of incident cases of colon cancer identified from records held by the North Western Regional Cancer Registry was used to simulate the effects on survival of changes in clinical and registration factors. The survival curve produced after each simulation was compared with that for aggregated data from 21 European registries.



Results

The observed survival differences were not explained by more effective primary treatment or by misclassification of in situ cases as malignant disease, whereas the exclusion of cases with only a clinical diagnosis produced estimates close to those of the European cohort.



Conclusion

The observed survival differentials may not be due to differences in the quality of care but may reflect the failure of some European registries to register all patients with advanced disease. © 1998 British Journal of Surgery Society Ltd

International differences in survival from colon cancer: more effective care versus less complete cancer registration.

The process of setting screening performance targets requires an estimate of what the incidence of breast cancer would have been in the population invited for screening if there had not been a screening programme. Before the introduction of the National Health Service breast screening programme in 1988 the incidence of breast cancer was already increasing in the population targeted for screening. To establish the incidence before screening the most recent complete data from all the regional cancer registries were collated. An age-period model was constructed to predict what these incidence rates might now have been if the screening programme had not been introduced. The model predicted that if prescreening trends continued (between 1987 and 1995) underlying incidence over this period would increase by 2.3 per 10,000 in women aged 50-54, 2.6 per 10,000 in women aged 55-59, and 2.9 per 10,000 in women aged 60-64. If the prescreening trends have continued then the use of a universal rate, applied across all calendar years and age groups, would seem to be inappropriate when setting targets.

https://journals.sagepub.com/doi/pdf/10.1177/096914139600300303

Reliability of underlying incidence rates for estimating the effect and efficiency of screening for breast cancer.

The NHS breast screening programme invites women aged 50-64 for screening every 3 years. In this programme the term interval cancer is applied to a breast cancer occurring within 3 years of a screening test with negative results. Substantially higher than anticipated rates of interval cancers have already been reported from the NHS breast screening programme, 1 2 and there is conflicting evidence on whether the survival rates of women with interval cancers are different from those of women with breast cancer occurring in an unscreened population. 3 4 Were interval cancers to have a worse prognosis than cancers in an unscreened population, the reduction in mortality from breast cancer in the screened population might be substantially less than predicted.

To interpret survival estimates for women with interval cancers requires identification of a suitable group of unscreened women for compari- son. In the context of a national screening programme this …

https://www.bmj.com/content/bmj/316/7134/832.1.full.pdf

Pat Prior

Papers

Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study

Is the three year breast screening interval too long? Occurrence of interval cancers in NHS breast screening programme's north western region

International differences in survival from colon cancer: more effective care versus less complete cancer registration.

Reliability of underlying incidence rates for estimating the effect and efficiency of screening for breast cancer.

Survival rates from interval cancer in NHS breast screening programme