Incidence Trends of Cervical Cancer in Adolescents and Young Adults: Brazilian Population Based Data

Abstract

Purpose:

High incidence rates for cervical cancer in adolescents and young adults (AYAs: 15–29 years) make this the most common carcinoma in Brazil. Our aim was to analyze the incidence trends for cervical cancer (CC) and in situ neoplasia (IsN) among this age group.

Methods:

Incidence data were extracted from 21 Brazilian population-based cancer registries (PBCRs). Tumors with behavior code/3 (malignant) were classified as CC. Tumors with behavior code/2 were classified as IsN. Age-adjusted and age-specific incidence rates were calculated for individuals aged 15–19 years, 20–24 years, and 25–29 years. Incidence trends were evaluated by joinpoint regression analyses.

Results:

The median incidence rate of CC for AYA in Brazil was 3.63 per 100,000, with the highest rate observed in Recife (27.50 per 100,000). Significant increase in incidence for CC was identified in two PBCRs, with decreased rates for three PBCRs. The median incidence rate of IsN was 16.78 per 100,000 and was highest in Roraima (93.37 per 100,000). Increased incidence rates for IsN were identified in six PBCRs, with significant decreases in two PBCRs.

Conclusion:

The incidence rate for CC among AYA in Brazil is high and warrants intervention in terms of both prevention and control.

Introduction

Cancer in adolescents and young adults (AYAs) comprises a heterogeneous group of tumors, accounts for ∼6% of all cancers, and manifests a different pattern of incidence versus childhood tumors (i.e., tumors in those aged <15 years). Cancer is 2.7-fold more common in the AYA group than in children and demonstrates the transition from pediatric to adult morphological subtypes that reflect this intermediate age group.¹ In Brazil, AYA denotes those aged 15–29 years, which constitutes 13.4% of the population.²

High incidence rates for cervical cancer (CC) in AYA make this the most common carcinoma in four of the five Brazilian regions (North, Northeast, Midwest, and South).³

Prevention against CC is well established for children and adolescents aged 9–13 years (Human papillomavirus—HPV vaccination) and for adults aged 25–64 years (Papanicolaou test screening) in Brazil.⁴ However, AYAs aged 14–24 years fall between these groups and are therefore especially vulnerable to CC. HPV infections are common in this age group and appear shortly after the onset of sexual activity, although lesions typically regress in 3 years, with progression to cancer negligable.⁵ Accurate data on incidence rates for CC in AYA are essential if we are to instigate changes to our current prevention and control programs. Relevant data are also critical for the establishment of educational strategies, improved prevention, detection, and survival rates. Our current aim was to analyze the incidence trends of CC and in situ neoplasia (IsN) in the Brazilian AYA group.

Methods

Data were retrieved from 21 Brazilian population-based cancer registries (PBCRs) located in the 5 Brazilian regions (North, Northeast, Midwest, South, and Southeast), 19 capital cities, 1 state (Roraima), and the Federal District according to the different time periods available. The last two editions of the International Classification of Diseases for Oncology (ICD-O2/ICD-O3) were used for coding of tumor morphology and behavior.^6,7 Tumors with behavior code/3 (malignant), and morphological subtypes 800 (neoplasia not specified—NOS), 801–808 (squamous cell neoplasia), 814–838 (adenocarcinoma), and others (excepting NOS, squamous cell neoplasia, and adenocarcinoma), were classified as CC. Tumors with behavior code/2 (noninvasive/in situ), and morphological subtypes 805 and 807 (squamous cell neoplasia) or 814–838 (adenocarcinoma), were classified as IsN.

Age-adjusted incidence rates (AAIRs) and age-specific incidence rates (ASIRs) per 100,000 women were calculated for all 21 PBCRs according to age group (i.e., those aged 15–19 years, 20–24 years, and 25–29 years). Median incidence rates, used to measure central tendency, allowed us to derive an overall assessment of the incidence rate for the five regions. AAIR was estimated by a direct method using estimates of the world population for groups aged <30 years. Interquartile range was used to describe the distribution of incidence rates.⁸

Information about quality indices was available in official home page of Brazilian PBCRs and can be seen in Table 1 (www2.inca.gov.br/wps/wcm/connect/estatisticas/site/home/rcbp).

Table 1.

Incidence Rates of Cervical Cancer in Adolescents and Young Adults

	15–19 years			20–24 years			25–29 years			15–29 years			Indices of data quality
Region/PBCR (period)	n	ASIR	95% CI	n	ASIR	95% CI	n	ASIR	95% CI	n	AAIR	95% CI	MV (%)	DCO (%)
North
Belém (2003–2007)	—	—	—	10	2.68	(1.45–4.93)	64	20.07	(15.72–25.63)	74	7.28	(5.62–8.95)	94.76	4.58
Manaus (2002–2006)	—	—	—	^*	1.92	(0.97–3.80)	56	16.11	(12.40–20.91)	64	5.77	(4.35–7.18)	88.66	3.56
Palmas (2000–2010)	—	—	—	^*	3.76	(1.60–8.81)	^*	7.39	(3.88–14.04)	14	3.57	(1.69–5.44)	93.88	4.08
Roraima (2006–2010)	—	—	—	^*	5.92	(2.71–12.92)	10	10.69	(5.80–19.68)	10	5.31	(2.70–7.92)	86.99	10.16
Northeast
Aracaju (2007–2011)	^*	0.75	(0.13–4.25)	^*	2.11	(0.72–6.20)	^*	6.07	(3.09–12.02)	12	2.89	(1.25–4.52)	96.17	1.91
Fortaleza (2002–2006)	^*	0.32	(0.08–1.18)	^*	1.55	(0.82–2.97)	32	6.38	(4.52–9.01)	43	2.66	(1.86–3.45)	96.37	2.80
João Pessoa (2006–2010)	^*	1.20	(0.33–4.38)	14	8.43	(5.02–14.16)	38	25.44	(18.53–34.91)	54	11.27	(8.26–14.28)	93.51	0.00
Natal (2001–2005)	—	—	—	^*	3.75	(1.81–7.74)	13	8.16	(4.76–13.96)	20	3.81	(2.13–5.48)	79.56	17.44
Recife (2006–2010)	53	14.77	(11.29–19.32)	96	26.53	(21.72–32.39)	146	42.79	(36.39–50.31)	295	27.50	(24.36–30.64)	92.79	3.15
Salvador (2001–2005)	—	—	—	12	1.64	(0.94–2.87)	15	2.46	(1.49–4.06)	27	1.31	(0.82–1.81)	83.81	12.46
Teresina (2000–2002)	^*	0.19	(0.03–1.10)	^*	0.71	(0.24–2.10)	^*	1.85	(0.85–4.05)	10	0.89	(0.33–1.45)	85.53	14.21
Midwest
Campo Grande (2008–2009)	—	—	—	^*	2.85	(0.78–10.40)	13	17.83	(10.43–30.52)	15	6.62	(3.27–9.97)	90.85	7.32
Cuiabá (2003–2007)	^*	2.14	(0.73–6.31)	^*	4.44	(2.03–9.69)	19	16.59	(10.61–25.90)	28	7.50	(4.71–10.28)	96.09	2.15
Distrito Federal (1999–2002)	^*	0.43	(0.11–1.56)	^*	1.47	(0.71–3.04)	42	10.12	(7.498–13.68)	51	3.86	(2.80–4.92)	92.20	2.76
Goiânia (2005–2009)	—	—	—	^*	2.20	(1.06–4.53)	32	11.80	(8.36–16.66)	39	4.48	(3.07–5.89)	NA	NA
Southeast
Belo Horizonte (2003–2007)	—	—	—	11	1.83	(1.02–3.28)	27	5.24	(3.60–7.62)	38	2.26	(1.54–2.99)	92.75	3.89
Vitória (2008–2012)	^*	0.28	(0.05–1.60)	^*	1.00	(0.39–2.56)	31	7.45	(5.25–10.57)	36	2.80	(1.89–3.72)	88.38	10.94
São Paulo (2006–2010)	16	0.18	(0.11–0.29)	81	0.91	(0.73–1.12)	198	2.36	(2.05–2.71)	295	1.11	(0.98–1.23)	NA	NA
South
Curitiba (2006–2010)	^*	0.26	(0.04–1.49)	^*	1.99	(1.00–3.92)	25	6.57	(4.44–9.69)	34	2.83	(1.88–3.78)	94.56	3.79
Florianópolis (2008–2010)	—	—	—	—	—	—	11	20.93	(11.68–37.48)	11	6.70	(2.74–10.65)	95.17	2.90
Porto Alegre (2002–2006)	—	—	—	^*	2.21	(1.07–4.57)	41	15.07	(11.11–20.44)	48	5.53	(3.96–7.09)	86.80	11.73
Median (IQR)		0.00	(0.00–0.32)		2.11	(1.55–3.75)		10.12	(6.38–16.59)		3.63	(2.80–6.62)	92.75	3.89

Less than 10 cases.

AAIR, age-adjusted incidence rate; ASIR, age-specific incidence rate; CI, confidence interval; DCO, death certification only; IQR, interquartile range; MV, microscopically verified; NA, not available; PBCR, population-based cancer registry.

Incidence trends were evaluated for those PBCRs with 8–10 years of reporting (14 PBCRs). Among these (14) PBCRs, three (Palmas, Roraima, and Teresina) were excluded as they had values of zero. Joinpoint regression analysis was performed to identify significant changes in incidence trends, with estimates generated for the annual average percentage change (AAPC). The optimal cut-point period for measuring trends is described elsewhere; significance was determined using the Monte Carlo Permutation method.^9,10 The protocol was approved by the Research Ethics Committee of Instituto Nacional de Câncer.

Results

Incidence rates of CC and IsN

The median AAIR for CC was 3.63 per 100,000, with comparable values for the Midwest (5.55 per 100,000), North (5.54 per 100,000), and South (5.53 per 100,000) and lower values in the Northeast (2.89 per 100,000) and Southeast (2.26 per 100,000) (Fig. 1). The greatest values for AAIR were those reported for Recife (27.5 per 100,000), João Pessoa (11.27 per 100,000), and Belém (7.28 per 100,000). The peak ASIR of CC, among all age groups (15–19 years, 20–24 years, and 25–29 years), was observed in Recife (Table 1).

FIG. 1.

Incidence rates of cervical cancer/in situ neoplasia in adolescents and young adults.

Concerning IsN, the median AAIR was 16.78 per 100,000 with the greatest values seen in Roraima (93.37 per 100,000), Curitiba (59.00 per 100,000), and Goiânia (58.97 per 100,000). For the Belém and Teresina PBCRs, rates of in situ/CC were <1 (0.47/0.94), while in the João Pessoa and Recife PBCRs, values were just over one (1.19/1.08). The ASIRs of both CC and IsN increase with age, and a large variation in incidence rate was seen across the PBCRs. For those aged 15–19 years, the highest ASIRs were seen in Curitiba, Aracaju, and Roraima; the highest rates for those aged 20–24 years and 25–29 years were seen in Roraima (Table 2).

Table 2.

Incidence Rates of In Situ Neoplasia in Adolescents and Young Adults

	15–19 years			20–24 years			25–29 years			15–29 years
Region/PBCR (period)	n	ASIR	95% CI	n	ASIR	95% CI	n	ASIR	95% CI	n	AAIR	95% CI	IsN/CC ratio
North
Belém (2003–2007)	^*	0.52	(0.14–1.90)	^*	2.41	(1.27–4.59)	25	7.84	(5.31–11.57)	36	3.47	(2.33–4.60)	0.47
Manaus (2002–2006)	^*	1.88	(0.95–3.70)	55	13.25	(10.18–17.24)	134	38.55	(32.55–45.65)	197	17.25	(14.83–19.66)	2.98
Palmas (2000–2010)	^*	4.02	(1.71–9.42)	^*	5.27	(2.55–10.88)	29	23.81	(16.58–34.20)	41	10.76	(7.46–14.05)	3.01
Roraima (2006–2010)	10	10.17	(5.52–18.72)	101	116.14	(95.60–141.08)	124	164.21	(137.75–195.73)	235	93.37	(81.41–105.33)	17.58
Northeast
Aracaju (2007–2011)	21	15.76	(10.31–24.09)	68	47.78	(37.69–60.56)	131	99.71	(84.04–118.29)	220	52.76	(45.79–59.74)	18.25
Fortaleza (2002–2006)	^*	0.9	(0.44–2.12)	45	7.83	(5.85–10.48)	65	12.97	(10.17–16.53)	116	7.00	(5.73–8.28)	2.63
João Pessoa (2006–2010)	^*	2.39	(0.93–6.18)	21	12.65	(8.27–19.34)	40	26.78	(19.66–36.46)	65	13.49	(10.20–16.77)	1.19
Natal (2001–2005)	^*	0.98	(0.26–3.58)	26	13.93	(9.51–20.42)	59	37.03	(28.71–47.75)	87	16.66	(13.15–20.17)	4.37
Recife (2006–2010)	22	6.13	(4.05–9.28)	109	30.12	(24.97–36.32)	191	55.97	(48.58–64.49)	322	29.76	(26.50–33.01)	1.08
Salvador (2001–2005)	11	1.51	(0.84–2.72)	66	9.05	(7.11–11.51)	139	22.84	(19.35–26.97)	216	10.75	(9.31–12.19)	8.20
Teresina (2000–2002)	^*	0.19	(0.03–1.10)	^*	1.19	(0.51–2.79)	^*	1.23	(0.48–3.18)	10	0.84	(0.31–1.38)	0.94
Midwest
Campo Grande (2008–2009)	^*	2.98	(0.82–10.87)	18	25.65	(16.23–40.56)	26	35.67	(26.58–55.52)	46	20.70	(14.71–26.70)	3.12
Cuiabá (2003–2007)	^*	5.01	(2.42–10.34)	54	40.01	(30.66–52.19)	116	101.27	(84.44–121.43)	177	47.01	(40.07–53.95)	6.26
Distrito Federal (1999–2002)	10	2.14	(1.16–3.94)	139	29.28	(24.80–34.57)	283	68.21	(60.71–76.63)	432	31.97	(28.95–34.99)	8.28
Goiânia (2005–2009)	32	10.47	(7.42–14.78)	162	51.50	(43.62–59.33)	328	121.00	(108.60–134.82)	522	58.97	(53.91–64.03)	13.16
Southeast
Belo Horizonte (2003–2007)	18	3.17	(2.00–5.02)	74	12.34	(9.83–15.49)	188	36.51	(31.65–42.11)	280	16.78	(14.80–18.74)	7.42
Vitória (2008–2012)	^*	0.56	(0.15–2.06)	39	9.71	(7.11–13.29)	71	17.06	(13.74–21.78)	112	8.77	(7.14–10.40)	3.13
São Paulo (2006–2010)	44	0.49	(0.36–0.66)	241	2.7	(2.38–3.06)	556	6.63	(6.10–7.20)	841	3.16	(2.95–3.37)	2.84
South
Curitiba (2006–2010)	71	18.71	(14.84–23.60)	245	60.85	(53.70–68.96)	390	102.45	(92.78–113.13)	706	59.00	(54.64–63.35)	20.84
Florianópolis (2008–2010)	^*	9.75	(4.16–22.83)	15	26.88	(16.29–44.35)	49	93.23	(70.53–123.23)	69	41.95	(32.04–51.85)	6.26
Porto Alegre (2002–2006)	^*	0.96	(0.32–2.83)	21	6.65	(4.35–10.16)	74	27.20	(21.66–34.14)	98	11.17	(8.96–13.39)	2.01
Median (IQR)		2.39	(0.96–6.13)		13.25	(7.83–30.12)		36.51	(22.84–93.23)		16.78	(10.75–41.95)

Less than 10 cases.

CC, cervical cancer; IsN, in situ neoplasia.

Incidence trends of CC and IsN

Figure 2 shows the incidence trends for all PBCRs, with significant increases in Belo Horizonte (AAPC +4.6) and João Pessoa (AAPC +12.6). In Aracaju (AAPC −13.8), Fortaleza (AAPC −7.7), and Goiânia (AAPC −14.0), important declines were reported.

FIG. 2.

Joinpoint of analysis incidence trends of cervical cancer/in situ neoplasia in adolescents and young adults. *Statistically significant. AAPC, average annual percent change.

IsN manifested a significantly increased incidence rate in Curitiba (AAPC +15.8), Goiânia (AAPC +14.0), Porto Alegre (AAPC +23.5), Recife (AAPC +22.8), Salvador (AAPC +33.4), and Belo Horizonte (AAPC +10.2). The cities of Belém (AAPC −26.2) and São Paulo (AAPC −7.7) showed a significant decline.

Discussion

CC and its precursor lesions can be easily diagnosed with screening programs and their methodologies are well documented. Screening supports diagnosis and helps to improve survival rates. In Brazil, CC is the most frequent tumor in the North region, the second in the Midwest and Northeast regions, the third in the Southeast, and the fourth tumor in the South, for all ages.¹¹ The 21 PBCRs cover ∼20% of Brazilian population. In Brazil, 1.5% of this case load arises in those aged 15–24 years.¹² From 2011 to 2015, cytopathological examinations were completed for 19% and 14% of those aged 15–24 years and 25–29 years, respectively.¹³ In our recent data, we observed a very high incidence rate of CC in Brazilian AYA. Among the group “carcinomas,” this cancer was the most frequent, with an incidence rate of 3.5 per 100,000.³

In comparison, for the period 2005 to 2007, population-based data from Canada demonstrated an incidence rate for invasive CC of <0.3 per 100,000 for those aged 15–19 years, 1.2 per 100,000 for those aged 20–24 years, and 6.3 per 100,000 for those aged 25–29 years.¹⁴ The National Cancer Registry of England described an incidence rate of 0.08 per 100,000 for adolescents (15–19) and 2.1 per 100,000 for those aged 20–24 years.¹⁵ An Australian database described a significantly decreased AAPC (−2.7%) among those aged 15–39 years.¹⁶ In a recent report from Korea, incidence rates of 0.04, 1.0, and 5.8 per 100,000 were reported for those aged 15–19 years, 20–24 years, and 25–29 years, respectively, with an increasing incidence rate observed for AYA.¹⁷ In a recent analysis of the SEER database (2007–2011), incidence rates for invasive CC were reported to be 0.1 per 100,000 (15–19 years), 1.5 per 100,000 (20–24 years), and 6.6 per 100,000 (25–29 years) among AYAs.¹⁸

The Brazilian median incidence rate is higher than those of developed countries. Recife, in the Northeast region, has one of the highest incidence rates of CC (27.5 per 100,000), which has increased from the rate of 19.3 per 100,000 recorded for 2005–2009.³

Incidence trends of IsN also increased significantly suggesting the influence of screening programs. In the South region (Curitiba, Florianópolis, and Porto Alegre), we observed a high incidence rate of CC, with Curitiba registering the highest incidence of IsN. Smoking is associated with an elevated risk for high-grade cervical intraepithelial neoplasia (CIN) in young women.¹⁹ The South region of Brazil is a worldwide leader in tobacco production and, despite a reduction in female Brazilian smokers, this region still has the highest rate of female smokers.^20,21 Smoking can contribute to pathogenesis by reactivating or prolonging HPV infection. Among those aged 15–19 years, a high incidence rate of IsN was seen in this (South) region. While it is well known that low grade lesions regress spontaneously in this age group, around 2%–15% can progress to CIN3 (IsN).^5,22–24

In addition, Soares et al. report correlates for risk factors such as the initiation of sexual activity and tobacco use in adolescents in the South region of Brazil.²⁴ Data from the Brazilian National Adolescents School-based Health Survey report that 27% of adolescents aged 13–15 years had initiated sexual activity.²⁵ Since 2014, vaccination against HPV has been recommended for girls aged 9–13 years by the Brazilian Health System through the CC program.²⁶ Recent data demonstrate a vaccine adherence rate of 74.2% nationally, with some variation across regions. The lowest adherence rate was in the North and Northeast regions (around 69%).²⁵

Pap smear testing in Brazil began in 1996, and, since 2011, has been recommended for all women aged 25–64 years following commencement of sexual activity. While it is well known that screening women aged <25 years increases the incidence rate by only 1%, our incidence rate in AYAs (<25 years) is extremely high.²⁷ Among four (19%) PBCRs, the ratio between IsN and CC is <1.19, suggesting that screening should be improved. Early diagnosis, sexual education, and access to treatment should all be emphasized. Increase in incidence rates of IsN across mostly all PBCRs draws attention; we believe that this is due to Brazilian CC screening program.

This study helps us to understand the incidence trends of CC in the AYA population and suggests possible causes. Furthermore, it also provides a framework with which to analyze future trends and assess the impact of prevention programs such as HPV vaccination. The main limitation of this study concerns the provision of data. PBCRs are only available for some Brazilian capitals and cities, making it impossible to derive accurate average statistics for the whole country. Another important limitation is discrepancies in describing this age group in several publications. In some studies, the AYA designation is reserved for those aged 15–24 years, 15–39 years, and even 15–49 years, making comparable analyses extremely difficult.^15,16,28

The data generated in this study point to a high incidence rate for CC in Brazil, particularly for the 15–29 years old age group. Therefore, improved prevention and control are necessary, with the success of future measures assessed by robust epidemiological data.

Footnotes

Acknowledgments

L.S.V. and N.V.B. have a scholarship from Instituto Nacional de Câncer. B.D.C. has a scholar grant from the National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq) (Brasília) (No. 306291/2014-2) and the Foundation for Support of Research in the State of Rio de Janeiro (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, FAPERJ) (Rio de Janeiro) (No. 212989-2016).

The authors are responsible for the content and writing of the article. L.S.V. and N.V.B. collected and analyzed the data. M.O.S., R.S.R., N.P.S., L.C.T., and B.D.C. discussed and interpreted the data. L.S.V., N.V.B., R.S.R., and B.D.C. wrote the article. All authors participated in the interpretation, read, and approved the final article.

Author Disclosure Statement

The authors report no conflicts of interest.

References

Bleyer

, Viny

, Barr

. Cancer in 15-to 29-year-olds by primary site. Oncologist. 2006; 11:590–601.

Ministério da Saúde. Instituto Brasileiro de Geografia e Estatística. Censo 2010. Accessed February 18, 2016 from: www.censo2010.ibge.gov.br/sinopse/webservice

Balmant

, de Souza Reis

, Pinto Oliveira

, et al. Cancer incidence among adolescents and young adults (15 to 29 years) in Brazil. J Pediatr Hematol Oncol. 2016; 38:e88–96.

Ministério da Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva. Diretrizes Brasileiras para o rastreamento do câncer do colo do útero, 2 ed rev atual. Rio de Janeiro: INCA, 2016. Accessed December 20, 2016 from: www1.inca.gov.br/inca/Arquivos/Diretrizes_para_o_Rastreamento_do_cancer_do_colo_do_utero_2016_corrigido.pdf

Moscicki

, Cox

. Practice improvement in cervical screening and management (PICSM): symposium on management of cervical abnormalities in adolescents and young women. J Low Genit Tract Dis. 2010; 14:73.

World Health Organization. International Classification of Diseases for Oncology, ICD-O—Second Edition. Geneva, Switzerland: WHO, 1990.

World Health Organization. International Classification of Diseases for Oncology, ICD-O—Third Edition. Geneva, Switzerland: WHO, 2000.

Doll

, Payne

, Watherhouse

JAH

. Cancer incidence in five continents Geneva, UICC volume 1. Berlin: Springer, 1996.

National Cancer Institute. Joinpoint Trend Analysis Software. Accessed May 10, 2016 from: https://surveillance.cancer.gov/joinpoint

10.

Kim

H-J

, Fay

, Feuer

, Midthune

. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000; 19:335–51.

11.

Ministério da Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva. Estimativa 2016: incidência de câncer no Brasil. Rio de Janeiro: INCA, 2015. Accessed January 10, 2016 from: www.inca.gov.br/estimativa/2016/estimativa-2016-v11.pdf

12.

Ministério da Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva. Incidência, mortalidade e morbidade hospitalar por câncer em crianças, adolescentes e adultos jovens no Brasil: informações dos registros de câncer e do sistema de mortalidade. Rio de Janeiro: INCA, 2016.

13.

Ministério da Saúde. DATASUS Departamento de Informática do SUS. Produção Ambulatorial do SUS. Accessed January 5, 2016 from: http://tabnet.datasus.gov.br/cgi/tabcgi.exe?sia/cnv/qbuf.def

14.

Popadiuk

, Stankiewicz

, Dickinson

, et al. Invasive cervical cancer incidence and mortality among Canadian women aged 15 to 29 and the impact of screening. J Obstet Gynaecol Can. 2012; 34:1167–76.

15.

Birch

, Alston

, Quinn

, Kelsey

. Incidence of malignant disease by morphological type, in young persons aged 12–24 years in England, 1979–1997. Eur J Cancer. 2003; 39:2622–31.

16.

Haggar

, Preen

, Pereira

, et al. Cancer incidence and mortality trends in Australian adolescents and young adults, 1982–2007. BMC Cancer. 2012; 12:151.

17.

Moon

, Park

, Oh

, et al. Cancer incidence and survival among adolescents and young adults in Korea. PLoS One. 2014; 9:e96088.

18.

National Cancer Institute. SEER cancer statistics review 1975–2000: adolescent and young adult cancer by site incidence, survival and mortality. Accessed April 26, 2016 from: http://seer.cancer.gov/archive/csr/1975_2011/results_merged/sect_32_aya.pdf

19.

Collins

, Rollason

, Young

, Woodman

. Cigarette smoking is an independent risk factor for cervical intraepithelial neoplasia in young women: a longitudinal study. Eur J Cancer. 2010; 46:405–411.

20.

Malta

, Vieira

, Szwarcwald

, et al. Smoking trends among Brazilian population-National Household Survey, 2008 and the National Health Survey, 2013. Rev Bras Epidemiol. 2015; 18:45–56.

21.

Haverkos

, Soon

, Steckley

, Pickworth

. Cigarette smoking and cervical cancer: part I: a meta-analysis. Biomed Pharmacother. 2003; 57:67–77.

22.

Moore

, Cofer

, Elliot

, et al. Adolescent cervical dysplasia: histologic evaluation, treatment, and outcomes. Am J Obstet Gynecol. 2007; 197:141.e1–6.

23.

Fuchs

, Weitzen

, Wu

, et al. Management of cervical intraepithelial neoplasia 2 in adolescent and young women. J Pediatr Adolesc Gynecol. 2007; 20:269–74.

24.

Soares

ALG

, Munhoz

, Goncalves

. Early sexual initiation and alcohol, tobacco and illicit drugs use among Brazilian adolescents (P 598). Healthy Living: The European Congress of Epidemiology. Eur J Epidemiol., 2015; 30:987.

25.

Ministério da Saúde. Instituto Brasileiro de Geografia e Estatística. Pesquisa Nacional de Saúde do Escolar, PeNSE 2015. Rio de Janeiro: IBGE, 2016. Accessed December 20, 2016 from: https://www.icict.fiocruz.br/sites/www.icict.fiocruz.br/files/PENSE_Saude%20Escolar%202015.pdf

26.

Ministério da Saúde.. Secretaria de Vigilância em Saúde. Departamento de Vigilância das Doenças Transmissíveis. Coordenação Geral do Programa Nacional de Imunizações. Informe técnico da vacina Papilomavírus Humano 6, 11, 16 e 18 (recombinante) 2015. Brasília: MS, 2015. Accessed April 15, 2016 from: www.cosemsrs.org.br/imagens/eventos/cli_c1d7.pdf

27.

International Agency for Research on Cancer. Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. IARC Working Group on evaluation of cervical cancer screening programmes. Br Med J., 1986; 293:659–64.

28.

, Vogtmann

, Zhang

, et al. Cancer incidence among adolescents and young adults in urban Shanghai, 1973–2005. PLoS One. 2012; 7:e42607.