HUMAN VACCINES & IMMUNOTHERAPEUTICS 2016, VOL. 12, NO. 6, 1373–1374 http://dx.doi.org/10.1080/21645515.2016.1162935
COMMENTARY
Will HPV vaccination affect cervical cancer morbidity and mortality world-wide? Rebecca Lucketta and Sarah Feldmanb a
Beth Israel Hospital, Harvard Medical School, Boston, MA, USA; bBrigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
ARTICLE HISTORY Received 22 February 2016; Accepted 1 March 2016 KEYWORDS cervical cancer; HPV vaccine; morbidity; mortality
There is considerable hope that HPV vaccination will dramatically reduce the morbidity and mortality associated with cervical cancer. Theoretically, the quadrivalent and bivalent vaccines could prevent 70% of cervical cancer and the nonavalent vaccine, 90%, however, the reality is not that simple. Cervical cancer is the fourth most commonly diagnosed cancer in women worldwide and the second in women in the developing world. Sub-Saharan Africa, Central America, the Caribbean, and south-central Asia have disproportionately high rates of cervical cancer compared to Europe, Australia, and North America. In 2012, there were 527,600 cases of newly diagnosed cervical cancer and 85% of these cases occurred in the developing world.1 Similarly, mortality from cervical cancer is disproportionately high in the developing world. Two out of every 3 women diagnosed with cervical cancer in sub-Saharan Africa will die from the disease, whereas only one in 3 will die in North America.2 But cervical cancer is preventable, diagnosable, and treatable, so why do we see such a dire situation for women in lowand middle- income countries (LMICs)? While effective screening has reduced the incidence of cervical cancer in high-income countries,3 there is limited availability of and access to these services in LMICs, and where they are available, the quality is variable.4,5 Early stage symptoms of cervical cancer are nonspecific, including vaginal discharge, irregular vaginal bleeding, and post-coital bleeding, and do not always prompt a patient to seek care. Thus, screening is essential, and life-saving: precancerous lesions identified through screening are treated to prevent progression to cervical cancer. Once cervical cancer develops, it is still curable if detected and treated in its earliest stages. Curative treatments are limited when patients present at advanced stages of disease. The International Federation of Gynecology and Obstetrics (FIGO) has established clinical staging criteria for cervical cancer.6 The FIGO stage at diagnosis is inversely related to prognosis.7,8 In developed countries, women are more frequently diagnosed at an early stage of disease through screening.9 Though data on stage at presentation are limited in the developing world, available data from Kenya and Zimbabwe show that over 80% of women in these countries present with advanced stage
CONTACT Sarah Feldman © 2016 Taylor & Francis
[email protected]
disease, a point at which curative options are extremely limited.10,11 These patients with advanced cervical cancer suffer significant end-stage morbidities, including hemorrhage, obstructive renal failure, leakage of urine or feces through vaginal fistulas caused by tumor invasion, lymphedema of the lower extremities, and severe low back and abdominal pain.12 Limited availability of treatment services are also a major factor behind the disproportionate morbidity and mortality in developing countries. Treatment for cervical cancer includes surgery, radical surgery, chemotherapy and radiation, either alone or in combination. Surgical options are limited to those with very early stage disease. Treatment beyond straightforward simple surgery requires specialists, equipment and infrastructure that are not available or affordable in many parts of the world, and many women do not even have access to basic radiation therapy services. Palliation of symptoms is also limited in resource-poor settings, exacerbating the impact of the late-stage morbidities that patients manifest.13 How is the HPV vaccine going to change all of this? Data on the bivalent, quadrivalent and the newest nonavalent vaccine are encouraging in that infection with high risk HPV, the oncogenic precursor to cervical cancer, could theoretically be prevented. However, the projected 70–90% reduction in cervical cancer that is forecasted is based on ideal study conditions, and assumes that all women are vaccinated before they are infected with the covered high risk types, that duration of immunogenicity is life-long, and that there is no change in the proportion of cancers caused by the non-covered vaccine types. What is the reality? As we have seen with screening and treatment programs, even when evidence-based interventions are known, their implementation in real clinical practice is far from perfect. In the case of HPV vaccination, there are several issues to consider: many women are already infected with HPV; vaccine acceptability has limited its uptake; vaccine schedules are rigorous; the duration of protection is unknown; and the vaccines are expensive, making access in LMICs challenging. While the HPV vaccine has great potential to protect the generation of young girls being vaccinated now, those
Division of Gynecologic Oncology, Brigham & Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA.
1374
R. LUCKETT AND S. FELDMAN
women already living with HPV infection still need improved access to effective screening programs and expanded treatment options. What does that mean for women and providers today? While the HPV vaccine will likely improve the morbidity and mortality from cervical cancer in the next generation, we must continue to advocate for comprehensive cervical cancer prevention programs for all women to change cervical cancer trends.
[5]
[6]
[7]
Disclosure of potential conflicts of interest No potential conflicts of interest were disclosed.
References [1] Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Ahmedin J. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65:87-108; PMID:25651787; http://dx.doi.org/10.3322/caac.21262. [2] Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. Eleven [Internet]. Lyon, France: International Agency for Research on Cancer. Available from http://globocan.iarc.fr. 2013. [3] Peirson L, Fitzpatrick-Lewis D, Ciliska D, Warren R. Screening for cervical cancer: a systematic review and meta-analysis. Syst Rev 2013; 2:35; PMID:23706117; http://dx.doi.org/10.1186/2046-4053-235. [4] Gakidou E, Nordhagen S, Obermeyer Z. Coverage of cervical cancer screening in 57 countries: low average levels and large inequalities.
[8] [9]
[10]
[11]
[12]
[13]
PLoS Med 2008; 5(6): e132; PMID:18563963; http://dx.doi.org/ 10.1371/journal.pmed.0050132. Bradford L, Goodman AK. Cervical cancer screening and prevention in low-resource settings. Clin Obstet Gynecol 2013: 56(1): 76-87; http://dx.doi.org/10.1097/GRF.0b013e31828237ac. Benedet JL, Bender H, Jones H, Ngan HYS, Pecorelli S. Staging classifications and clinical practice guidelines of gynaecologic cancers. Int J Gynecol Obstet 2000; 70:207-312; http://dx.doi.org/10.1016/S00207292(00)00300-3. Randall M, Fracasso P, Toita T, Tedjarati S, Michael H, 2013, Cervix, in Barakat R, Berchuck A, Marman M, Randall M, ed., Principles and practice of gynecologic oncology, Lippincott Williams & Wilkins, Philadelphia, p.611-612. Garner E. Cervical cancer disparities in screening, treatment and survival. Can Epidemiol Biomarkers Prev 2003; 12:242s. Pretorius R, Semrad N, Watring W, Fotheringham N. Presentation of cervical cancer. Gynecol Oncol 1991; 42(1):48-53; http://dx.doi.org/ 10.1016/0090-8258(91)90229-X. Maranga I, Hampson L, Oliver A, Gamal A, Gichangi P, Opiyo A, Holland CM, Hampson IN. Analysis of factors contributing to the low survival of cervical cancer patients undergoing radiotherapy in Kenya. Plos 2013; 8(10):e78411; http://dx.doi.org/10.1371/journal.pone.0078411. Ndiovu N, Kambarami R. Factors associated with tumour stage at presentation in invasive cervical cancer. Centr Afr J med 2003; 49(9– 10):107-11. World Health Organization. Comprehensive cervical cancer control: A guide to essential practice. Australia, 2014. Available at: http://apps.who. int/iris/bitstream/10665/144785/1/9789241548953_eng.pdf?ua=1. World Health Organization. WHO guidance note: comprehensive cervical cancer prevention and control: a healthier future for girls and women. Geneva 2013. http://www.who.int/reproductivehealth/ publications/cancers/9789241505147/en/
COMMENTARY
Will HPV vaccination affect cervical cancer morbidity and mortality world-wide? Rebecca Lucketta and Sarah Feldmanb a
Beth Israel Hospital, Harvard Medical School, Boston, MA, USA; bBrigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
ARTICLE HISTORY Received 22 February 2016; Accepted 1 March 2016 KEYWORDS cervical cancer; HPV vaccine; morbidity; mortality
There is considerable hope that HPV vaccination will dramatically reduce the morbidity and mortality associated with cervical cancer. Theoretically, the quadrivalent and bivalent vaccines could prevent 70% of cervical cancer and the nonavalent vaccine, 90%, however, the reality is not that simple. Cervical cancer is the fourth most commonly diagnosed cancer in women worldwide and the second in women in the developing world. Sub-Saharan Africa, Central America, the Caribbean, and south-central Asia have disproportionately high rates of cervical cancer compared to Europe, Australia, and North America. In 2012, there were 527,600 cases of newly diagnosed cervical cancer and 85% of these cases occurred in the developing world.1 Similarly, mortality from cervical cancer is disproportionately high in the developing world. Two out of every 3 women diagnosed with cervical cancer in sub-Saharan Africa will die from the disease, whereas only one in 3 will die in North America.2 But cervical cancer is preventable, diagnosable, and treatable, so why do we see such a dire situation for women in lowand middle- income countries (LMICs)? While effective screening has reduced the incidence of cervical cancer in high-income countries,3 there is limited availability of and access to these services in LMICs, and where they are available, the quality is variable.4,5 Early stage symptoms of cervical cancer are nonspecific, including vaginal discharge, irregular vaginal bleeding, and post-coital bleeding, and do not always prompt a patient to seek care. Thus, screening is essential, and life-saving: precancerous lesions identified through screening are treated to prevent progression to cervical cancer. Once cervical cancer develops, it is still curable if detected and treated in its earliest stages. Curative treatments are limited when patients present at advanced stages of disease. The International Federation of Gynecology and Obstetrics (FIGO) has established clinical staging criteria for cervical cancer.6 The FIGO stage at diagnosis is inversely related to prognosis.7,8 In developed countries, women are more frequently diagnosed at an early stage of disease through screening.9 Though data on stage at presentation are limited in the developing world, available data from Kenya and Zimbabwe show that over 80% of women in these countries present with advanced stage
CONTACT Sarah Feldman © 2016 Taylor & Francis
[email protected]
disease, a point at which curative options are extremely limited.10,11 These patients with advanced cervical cancer suffer significant end-stage morbidities, including hemorrhage, obstructive renal failure, leakage of urine or feces through vaginal fistulas caused by tumor invasion, lymphedema of the lower extremities, and severe low back and abdominal pain.12 Limited availability of treatment services are also a major factor behind the disproportionate morbidity and mortality in developing countries. Treatment for cervical cancer includes surgery, radical surgery, chemotherapy and radiation, either alone or in combination. Surgical options are limited to those with very early stage disease. Treatment beyond straightforward simple surgery requires specialists, equipment and infrastructure that are not available or affordable in many parts of the world, and many women do not even have access to basic radiation therapy services. Palliation of symptoms is also limited in resource-poor settings, exacerbating the impact of the late-stage morbidities that patients manifest.13 How is the HPV vaccine going to change all of this? Data on the bivalent, quadrivalent and the newest nonavalent vaccine are encouraging in that infection with high risk HPV, the oncogenic precursor to cervical cancer, could theoretically be prevented. However, the projected 70–90% reduction in cervical cancer that is forecasted is based on ideal study conditions, and assumes that all women are vaccinated before they are infected with the covered high risk types, that duration of immunogenicity is life-long, and that there is no change in the proportion of cancers caused by the non-covered vaccine types. What is the reality? As we have seen with screening and treatment programs, even when evidence-based interventions are known, their implementation in real clinical practice is far from perfect. In the case of HPV vaccination, there are several issues to consider: many women are already infected with HPV; vaccine acceptability has limited its uptake; vaccine schedules are rigorous; the duration of protection is unknown; and the vaccines are expensive, making access in LMICs challenging. While the HPV vaccine has great potential to protect the generation of young girls being vaccinated now, those
Division of Gynecologic Oncology, Brigham & Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA.
1374
R. LUCKETT AND S. FELDMAN
women already living with HPV infection still need improved access to effective screening programs and expanded treatment options. What does that mean for women and providers today? While the HPV vaccine will likely improve the morbidity and mortality from cervical cancer in the next generation, we must continue to advocate for comprehensive cervical cancer prevention programs for all women to change cervical cancer trends.
[5]
[6]
[7]
Disclosure of potential conflicts of interest No potential conflicts of interest were disclosed.
References [1] Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Ahmedin J. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65:87-108; PMID:25651787; http://dx.doi.org/10.3322/caac.21262. [2] Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. Eleven [Internet]. Lyon, France: International Agency for Research on Cancer. Available from http://globocan.iarc.fr. 2013. [3] Peirson L, Fitzpatrick-Lewis D, Ciliska D, Warren R. Screening for cervical cancer: a systematic review and meta-analysis. Syst Rev 2013; 2:35; PMID:23706117; http://dx.doi.org/10.1186/2046-4053-235. [4] Gakidou E, Nordhagen S, Obermeyer Z. Coverage of cervical cancer screening in 57 countries: low average levels and large inequalities.
[8] [9]
[10]
[11]
[12]
[13]
PLoS Med 2008; 5(6): e132; PMID:18563963; http://dx.doi.org/ 10.1371/journal.pmed.0050132. Bradford L, Goodman AK. Cervical cancer screening and prevention in low-resource settings. Clin Obstet Gynecol 2013: 56(1): 76-87; http://dx.doi.org/10.1097/GRF.0b013e31828237ac. Benedet JL, Bender H, Jones H, Ngan HYS, Pecorelli S. Staging classifications and clinical practice guidelines of gynaecologic cancers. Int J Gynecol Obstet 2000; 70:207-312; http://dx.doi.org/10.1016/S00207292(00)00300-3. Randall M, Fracasso P, Toita T, Tedjarati S, Michael H, 2013, Cervix, in Barakat R, Berchuck A, Marman M, Randall M, ed., Principles and practice of gynecologic oncology, Lippincott Williams & Wilkins, Philadelphia, p.611-612. Garner E. Cervical cancer disparities in screening, treatment and survival. Can Epidemiol Biomarkers Prev 2003; 12:242s. Pretorius R, Semrad N, Watring W, Fotheringham N. Presentation of cervical cancer. Gynecol Oncol 1991; 42(1):48-53; http://dx.doi.org/ 10.1016/0090-8258(91)90229-X. Maranga I, Hampson L, Oliver A, Gamal A, Gichangi P, Opiyo A, Holland CM, Hampson IN. Analysis of factors contributing to the low survival of cervical cancer patients undergoing radiotherapy in Kenya. Plos 2013; 8(10):e78411; http://dx.doi.org/10.1371/journal.pone.0078411. Ndiovu N, Kambarami R. Factors associated with tumour stage at presentation in invasive cervical cancer. Centr Afr J med 2003; 49(9– 10):107-11. World Health Organization. Comprehensive cervical cancer control: A guide to essential practice. Australia, 2014. Available at: http://apps.who. int/iris/bitstream/10665/144785/1/9789241548953_eng.pdf?ua=1. World Health Organization. WHO guidance note: comprehensive cervical cancer prevention and control: a healthier future for girls and women. Geneva 2013. http://www.who.int/reproductivehealth/ publications/cancers/9789241505147/en/
