Eric J. Suba

Systems Analysis of Real-World Obstacles to Successful Cervical Cancer Prevention in Developing Countries

Papanicolaou screening is feasible anywhere that screening for cervical cancer, the leading cause of cancer-related death among women in developing countries, is appropriate. After documenting that the Vietnam War had contributed to the problem of cervical cancer in Vietnam, we participated in a grass roots effort to establish a nationwide cervical cancer prevention program in that country and performed root cause analyses of program deficiencies. We found that real-world obstacles to successful cervical cancer prevention in developing countries involve people far more than technology and that such obstacles can be appropriately managed through a systems approach focused on programmatic quality rather than through ideological commitments to technology. A focus on quality satisfies public health goals, whereas a focus on technology is compatible with market forces.

Association between war and cervical cancer among Vietnamese women

Decades ago, cervical cancer was the leading form of cancer among women in both North Vietnam and South Vietnam. Currently, cervical cancer rates are considerably lower in the northern region of the country. We performed a case‐control study to measure factors associated with the development of cervical cancer among Vietnamese women. Questionnaire‐based interviews were conducted with 202 women in southern Vietnam and 97 women in northern Vietnam. Case subjects were women hospitalized with cervical cancer. Control subjects were women hospitalized with extrauterine neoplasms. Data were analyzed using logistic regression, and odds ratios for the development of invasive cervical cancer were measured. The development of invasive cervical cancer was significantly associated with military service by husbands during the Second Indochinese War and with parity status. Odds ratio for the development of cervical cancer among southern Vietnamese women whose husbands had served in the armed forces was 2.6 (95% CI = 1.2–5.5). Odds ratio for the development of cervical cancer among northern women whose husbands had served in the armed forces was 3.9 (95% CI = 1.5–10.4) if their husbands had been stationed in South Vietnam during the war years. Northern women whose husbands had served in the military experienced no significant increase in cervical cancer risk if their husbands had been stationed in North Vietnam during the war years. Geographic and temporal variation in cervical cancer rates among Vietnamese women was associated with the movement of soldiers. These findings may be useful for cervical cancer prevention efforts in Vietnam and in other countries.

Papanicolaou screening in developing countries: An idea whose time has come

Cervical cancer is the leading cause of cancer-related death among women in developing countries. Although progress is optional in all settings, Papanicolaou screening is feasible anywhere that cervical screening is appropriate and should be implemented without further delay in high-risk communities with access to curative treatment services. Successful prophylactic cervical cancer vaccines, prospects for which remain uncertain, will not eliminate requirements for cervical screening. The feasibility of human papillomavirus test analysis has not been demonstrated in low-resource developing country settings. Because past failures of cervical screening in developing countries are attributable to failures in programmatic quality rather than to technological limitations of the screening test, a shift in paradigmatic focus from technology toward quality is mandatory. Because visual screening techniques coupled with immediate ablative treatment are rendered obsolete by an embedded quality-control paradox, a moratorium should be placed on all such programs. Considerable opportunity costs, borne by the underserved, are associated with prioritizing research of novel interventions in developing countries when satisfactory interventions already exist.

Papanicolaou Screening in Developing Countries

Cervical cancer is the leading cause of cancer-related death among women in developing countries. Although progress is optional in all settings, Papanicolaou screening is feasible anywhere that cervical screening is appropriate and should be implemented without further delay in high-risk communities with access to curative treatment services. Successful prophylactic cervical cancer vaccines, prospects for which remain uncertain, will not eliminate requirements for cervical screening. The feasibility of human papillomavirus test analysis has not been demonstrated in low-resource developing country settings. Because past failures of cervical screening in developing countries are attributable to failures in programmatic quality rather than to technological limitations of the screening test, a shift in paradigmatic focus from technology toward quality is mandatory. Because visual screening techniques coupled with immediate ablative treatment are rendered obsolete by an embedded quality-control paradox, a moratorium should be placed on all such programs. Considerable opportunity costs, borne by the underserved, are associated with prioritizing research of novel interventions in developing countries when satisfactory interventions already exist.

RE: Population-Level Impact of the Bivalent, Quadrivalent, and Candidate Nonavalent Human Papillomavirus Vaccines: A Comparative Model–Based Analysis

In a recent article in the Journal, Van de Velde et al. (1) assume that human papillomavirus (HPV) vaccines “prevent infection but do not alter the natural history of disease in individuals already infected by a vaccine type.” We question whether this assumption is correct. In 2006, the US Food and Drug Administration (FDA) expressed concerns about “the potential for Gardasil to enhance disease among a subgroup of subjects who had evidence of persistent infection with vaccine-relevant HPV types at baseline” (2). The increase in high-grade cervical disease rates among a subgroup of vaccinated girls and women noted by the FDA was not statistically significant. However, a subsequent ecological study of approximately 2.9 million Australian girls and women (3) documented that the introduction of Gardasil was associated with statistically significant increases in high-grade cervical disease rates among women aged more than 21 years but with statistically significant decreases in high-grade cervical disease rates among girls and women aged less than 18 years. Decreases in high-grade cervical disease rates among Australian girls and women aged less than 18 years were considered evidence of beneficial effect from Australia’s HPV vaccination program (3). However, to our knowledge, no explanations have been offered for the increases in high-grade cervical disease rates reported from the same study among Australian women aged more than 21 years. We ask Van de Velde et al. to consider whether the ecological observations from Australia suggest that Gardasil may in fact be enhancing disease among a subgroup of vaccinated individuals. In an accompanying editorial, Sahasrabuddhe and Sherman (4) claim that “HPV vaccination provides the scientific and public health community an unprecedented opportunity to reduce the burden of cervical cancer.” We question the scientific accuracy of this claim. Should perfect HPV vaccine efficacy last less than 15 to 20 years, HPV vaccination will prove to have been a “costly failed public health experiment in cancer control” (5). The best-case scenario modelled by Van de Velde et al., which includes an assumption of lifelong, perfect HPV vaccine efficacy, predicts that HPV vaccination will reduce cervical cancer rates by approximately 30% over 70 years (1). In contrast, the US Preventive Services Task Force has determined that Papanicolaou cytology screening reduces cervical cancer rates by 60% to 90% within 3 years of its introduction to populations naive to screening and that these reductions of disease burden are “‘consistent and equally dramatic across populations”‘ (6). Even if HPV vaccines eventually prove to confer lifelong perfect efficacy, we question whether the introduction of HPV vaccines to resource-constrained settings will decelerate coverage of target demographic groups by cervical screening services and thereby decelerate rather than accelerate global reductions in cervical cancer–related mortality (7).

Direct visual inspection for cervical cancer screening.

for their report on direct visualinspection for cervical carcinoma screening. However, we ques-tion their recommendation to link visual inspection with immediateablative treatment, an experimental strategy that they refer to as‘screen and treat’.Because poor-quality cervical screening programs can do moreharm than good, and because entropy is real, cervical screeningprograms require routine audits.

Human papillomavirus screening for low and middle-income countries

Worldwide, more than 85% of cervical cancer deaths occur in low andmiddle-income countries (LMICs) (Ferlay et al., 2013).We are concerned by Mark Schiffmans claim that “cervical cytology, which must be frequently repeated to achieve sufficient sensitivity, has failed to extend beyondhigh-resource environments despitemanydecades of Public Health effort.” (Schiffman, 2017) Schiffmans claim overlooks the example of cervical cytology screening in Vietnam, (Suba et al., 2001; Suba et al., 2012) which Schiffman acknowledged to be a success in 2011 (Suba et al., 2011). Schiffmans claim that cervical cytology screening has encountered only failure in LMICs is therefore inaccurate, yet exemplifies inaccurate statements from other international experts that undermine political support for cervical cytology screening in LMICs. For example, since at least 2001, international experts with the Alliance for Cervical Cancer Prevention have stated that they are “loath” to recommend the introduction of cervical cytology screening to LMICs, (Suba et al., 2012) and have persisted in reiterating false claims that cervical cytology screening is not feasible in LMICs (Tsu and Jeronimo, 2016). In 2011, Schiffman also acknowledged that “no clinically validated [human papillomavirus (HPV)] test is commercially available that is inexpensive enough to allow widespread implementation in LMICs.” (Suba et al., 2011)We ask Schiffman to statewhether there is, currently, a clinically validated HPV test that is inexpensive enough to allowwidespread implementation in LMICs. If such an HPV test is available, we ask Schiffman to specify its manufacturer and its price. If no such HPV test is currently available, then recommendations to implement HPV screening in LMICs remain unrealistic. Moreover, given current opposition from international experts to implementing cytology screening in LMICs, visual screening methods become, by default, the only feasible screening methods for LMICs empowered by the political support of recommendations from international experts. Even in the hands of international experts, visual screening methods have proven problematic (Suba et al., 2017). In LMICs, cytology, in addition to its traditional role as a primary screening test, will also be useful for screening younger women in future HPV-based screening programs and for triage of women with positive HPV primary screening tests (Suba et al., 2012). We ask Schiffman to acknowledge that cytology is a feasible and highly appropriate screening method for LMICs during the technological transition to

Eleven questions regarding cervical cancer prevention in India

Nevertheless, since 1998, three separate randomized trials in India funded by the US National Cancer Institute (NCI) and the Bill and Melinda Gates Foundation have compared, in aggregate, cervical cancer death rates among 224,929 women offered cervical screening to cervical cancer death rates among 138,624 women offered no screening whatsoever. To date, at least 254 women in unscreened control groups have died from cervical cancer.

Unethical randomised controlled trial of cervical screening in India: US Freedom of Information Act disclosures

This paper has been withdrawn. After acceptance it was inadvertently published online while awaiting legal review. It has now been withdrawn on legal advice. For the official publisher note please see: http://gh.bmj.com/content/2/2/bmjgh-2016-000177notice

Cervical cancer mortality in India.

1804 www.thelancet.com Vol 383 May 24, 2014 1 Stenberg K, Axelson H, Sheehan P, et al. Advancing social and economic development by investing in women’s and children’s health: a new Global Investment Framework. Lancet 2014; 12: 1333–54. 2 Partnership for Maternal, Newborn & Child Health, WHO, Aga Khan University. Essential interventions, commodities and guidelines: a global review of key interventions related to reproductive, maternal, newborn and child health. http://www.who.int/pmnch/ knowledge/publications/201112_essential_ interventions/en/index1.html (accessed April 22, 2014). 3 Alkire BC, Vincent JR, Burns CT, Metzler IS, Farmer PE, Meara JG. Obstructed labor and caesarean delivery: the cost and benefi t of surgical intervention. PLoS One 2012; 7: e34595. 4 Pereira C, Cumbi A, Malalane R, et al. Meeting the need for emergency obstetric care in Mozambique: work performance and histories of medical doctors and assistant medical offi cers trained for surgery. BJOG 2007; 114: 1530–33.