15. Screening in women who have experienced early sexual activity or have been victims of sexual abuse

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Background

Human papillomavirus (HPVHuman papillomavirus) infection often occurs shortly after first sexual activity.[1] HPV infections are more likely to occur in adolescent women than in older women, as the process of squamous metaplasiaIn the cervix this refers to the transformation of endocervical columnar epithelium to squamous epithelium, described as metaplastic squamous epithelium. of the transformation zone of the cervix is more active during adolescence and represents a vulnerability to the establishment of HPV infections.[2] There is also evidence that individuals who have been victims of sexual abuse as children have higher rates of anogenital HPV detection than individuals with no such history.[3]

Women who experience first sexual activity at an early age and are subsequently infected with oncogenic HPV may have a higher risk of carcinogenesis over time if these infections are persistent, since persistent infections are associated with an increased risk of cervical cancer.[4] Most HPV infections are transient and are cleared in adolescents and young women without the detection of cervical intraepithelial neoplasia (CINCervical Intraepithelial NeoplasiaRefers to abnormal changes in the cells on the surface of the cervix that are seen using a microscope (i.e. histologically-confirmed).CIN 1 – Mild dysplasiaCIN 2 – Moderate dysplasiaCIN 3 – Severe dysplasia to carcinoma in situ(The term CIN 2+ refers to CIN 2, 3, or invasive cervical cancer; CIN3+ refers to CIN 3 or invasive cervical cancer)CIN 2/3 refers to CIN 2 or CIN 3.) within 36 months.[5]

The incidence of cervical cancer in women younger than 25 years of age is very low. Since the introduction of the National Cervical Screening Program (NCSPNational Cervical Screening ProgramA joint program of the Australian, state and territory governments. It aims to reduce morbidity and mortality from cervical cancer, in a cost-effective manner through an organised approach to cervical screening. The program encourages women in the target population to have regular Pap smears.), age-specific incidence rates in this group of women have remained relatively stable over the past two decades.[6] The introduction of the National HPV Vaccination Program, which offers the HPV vaccine to girls at age 12–13 years, provides an additional level of protection for young women. Furthermore, there is some evidence that vaccination of women after first sexual intercourse may prevent reinfection or reactivation of the disease with vaccine included HPV types.[7]

The prevalence of vaccine-included HPV types 16/18/6/11 is now very low in young women, and has reduced by 35% since 2005–2007 in unvaccinated women, as well as in vaccinated women.[8] HPV 16 is the dominant contributor to cervical cancer and precancer in young women; prior to HPV vaccination, HPV 16 was detected in 70% of CIN grade 3 (CIN3) in women aged 16–25 years.[9]

Since the introduction of the National HPV Vaccination Program, there has been a steady decline in the detection of high-grade abnormalities in women under 20 years of age[6] and a reduction in the risk of high-grade cervical abnormalities in women who completed the vaccine series at the ages of 12–26 and who had not started screening before the implementation of the vaccination program.[10]

Note Anogenital HPV infections are transmitted mainly by skin-to-skin or mucosa-to-mucosa contact. Penetrative sexual intercourse is not strictly necessary for transmission and HPV can be transferred to the cervix from original infection at the introitus. Therefore, genital skin-to-skin contact, vaginal sex, oral sex, and anal sex represent types of sexual activity that may facilitate the person-to-person transmission of anogenital types of HPVHuman papillomavirus.


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Evidence

Systematic review evidence

No randomised or pseudorandomised controlled trials were found that evaluated the safety and effectiveness of alternative screening strategies in women with a history of early sexual intercourse or sexual abuse in comparison to other women.

General literature review evidence

In the absence of any direct evidence from the systematic review, a general review of the literature was performed to ascertain the effectiveness of cervical screening in:

  • women who have had first sexual intercourse at the age of 14 years or younger
  • women who had been sexually abused as children.

Sixteen studies were identified. No studies directly addressed the clinical question. However, one study provided indirect evidence based on the re-analysis of individual data from studies on cervical cancer risk conducted worldwide.[11] In this study, the relative risk for invasive cervical carcinoma in women who first had intercourse at the age of 14 years or younger was similar to the risk in women who first had intercourse at 16–18 years of age. In Australia, the median age at first sexual intercourse has been estimated to be 16–17 years of age.[12][13]

Although a number of studies were identified by the search, no other recent studies reported relevant outcome data by age of sexual debut. Studies found that regression of cervical abnormalities was common in young women[5][14][15][16] and that CIN3+ was rare.[17][18][19][20][16]

There is a lack of evidence that women who have experienced early sexual intercourse will benefit from commencing cervical screening before age 25 years.


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Recommendations

MSACThe Australian Medical Services Advisory Committee evidence-based recommendationQuestion mark transparent.png

REC15.1: Routine cervical screening is not recommended in young women
Routine cervical screening is not recommended in women under the age of 25 years.

Consensus-based recommendationQuestion mark transparent.png

REC15.2: Early sexual activity and cervical screening in young women
For women who experienced first sexual activity at a young age (<14 years) and who had not received the HPV vaccine before sexual debut, a single HPV test between 20 and 24 years of age could be considered on an individual basis.

Consensus-based recommendationQuestion mark transparent.png

REC15.3: Women with abnormal vaginal bleeding
Women at any age who have signs or symptoms suggestive of cervical cancer or its precursors, should have a co-testHPV test and LBC both requested and performed on a cervical sample. and be referred for appropriate investigation to exclude genital tract malignancy.

Co-testingHPV test and LBC both requested and performed on a cervical sample. (HPV and LBCLiquid based cytology(LBC) is a way of preparing cervical samples for examination in the laboratory.) is recommended as the presence of blood has the potential to adversely affect the sensitivity of any of the available tests.

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Benefits and harms

The minimal benefits of cervical screening in young women should be weighed against the increased risk of harm that unnecessary excisional procedures could have for future obstetric outcomes (see Chapter 14. Screening in Pregnancy) and psychosocial well-being (see Chapter 19. Pyschosocial care).

Positive oncogenic HPV test results and mild cytological abnormalities are frequently encountered in women younger than 25 years. However, high rates of regression of low and high-grade CIN lesions have been reported in the literature and the positive predictive value of cytology screening tests appears to be lower in this age group.[16][17]

Investigation and potential treatment of these lesions, that will most likely regress, may lead to unnecessary harms (psychosocial, obstetric and financial). It is considered that the harms outweigh the benefits for young women.

See Chapter 5. Benefits, harms and cost-effectiveness of cervical screening in the renewed NCSP.

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Health system implications of these recommendations

Clinical practice

A single cervical screening test may be performed before 25 years of age in women for whom there is concern about early sexual activity or sexual abuse prior to age 14 years. These are considered to be special circumstances and are not applicable to the general population of women under 25 years of age. A significant proportion of women experience their first sexual intercourse at age 14–16 years.[21] It is far less common for women to have first intercourse at age 13 years and below, and this may be more often related to sexual abuse.[21] This data supports confining our recommendations to women who have experienced early sexual activity or been victims of sexual abuse prior to the age of 14 years. Recommendations regarding symptomatic women are consistent with current clinical practice.

Resourcing

This recommendation is considered unlikely to require significant resources provided that cervical screening test providers restrict the screening of women under 25 years of age to those in whom the sexual history confirms either early sexual activity or sexual abuse (prior to 14 years of age) and on a case-by-case basis.

Barriers to implementation

Young women may choose not to disclose their age of first sexual activity or that they have a history of sexual abuse. However, as there is a lack of evidence that women with early sexual activity will benefit from commencing cervical screening earlier than 25 years of age, this is unlikely to affect safety in regard to the development of cervical cancer in these young women.

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Discussion

Unresolved issues

Uncertainty remains as to whether early sexual activity increases the risk of cervical cancer in young women as there is no currently available evidence to support an increased risk. The National HPV Vaccination Program is expected to reduce the number of at-risk women although the overall impact of vaccination will depend on how many young women were HPV-naïve before being vaccinated. Substantial indications of the effect of the National HPV Vaccination Program have already been observed in women including a reduction in the risk of high-grade cervical abnormalities in women who completed the vaccine series at the ages of 12–26 and who had not started screening before the implementation of the vaccination program,[10] a decline in the detection of high-grade abnormalities in women under 25 years of age[6] and a substantial decline in the prevalence of vaccine-included HPV types in women aged 18–24 years.[8] HPV vaccination is also expected to reduce the risk of high-grade abnormalities in unvaccinated women indirectly, via a reduction in the circulation of vaccine included HPV types within the population. A recent observational study reported a reduction in the prevalence of HPV 16/18Only HPV types 16 and or 18 detected using routine HPV screening tests in laboratory./6/11 in unvaccinated young women in Australia since the implementation of HPV vaccination, suggesting herd immunity.[8]

Nevertheless, vaccination should not be withheld from women post sexual debut as there is some evidence of protection even in women who were exposed to HPV prior to being vaccinated,[7] in addition to protection against any vaccine included HPV types to which they have not been previously exposed to.

Future research priorities

Prospective cohort studies following women from the age at first sexual activity until the age of CIN3 diagnosis, with regular interval follow-up, are required to ascertain the importance of early first sexual activity in the development of cervical pre-cancer.

Effectiveness of post-exposure HPV vaccination of young women and correlation with type of HPV in those found to have a positive oncogenic HPV test result.


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References

  1. Collins S, Mazloomzadeh S, Winter H, Blomfield P, Bailey A, Young LS, et al. High incidence of cervical human papillomavirus infection in women during their first sexual relationship. BJOG 2002 Jan;109(1):96-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11845815.
  2. Moscicki AB. HPV infections in adolescents. Dis Markers 2007;23(4):229-34 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17627058.
  3. Unger ER, Fajman NN, Maloney EM, Onyekwuluje J, Swan DC, Howard L, et al. Anogenital human papillomavirus in sexually abused and nonabused children: a multicenter study. Pediatrics 2011 Sep;128(3):e658-65 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21844060.
  4. Kjær SK, Frederiksen K, Munk C, Iftner T. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst 2010 Oct 6;102(19):1478-88 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20841605.
  5. 5.05.1 Insinga RP, Perez G, Wheeler CM, Koutsky LA, Garland SM, Leodolter S, et al. Incident cervical HPV infections in young women: transition probabilities for CIN and infection clearance. Cancer Epidemiol Biomarkers Prev 2011 Feb;20(2):287-96 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21300618.
  6. 6.06.16.2 Australian Institute of Health and Welfare. Cervical screening in Australia 2012–2013. Cancer series no. 93. Cat. no. CAN 91. Canberra: AIHWAustralian Institute of Health and Welfare; 2015 Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129550872.
  7. 7.07.1 Olsson SE, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, et al. Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection. Hum Vaccin 2009 Oct;5(10):696-704 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19855170.
  8. 8.08.18.2 Tabrizi SN, Brotherton JM, Kaldor JM, Skinner SR, Liu B, Bateson D, et al. Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study. Lancet Infect Dis 2014 Oct;14(10):958-66 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25107680.
  9. Brotherton JM, Tabrizi SN, Garland SM. Does HPV type 16 or 18 prevalence in cervical intraepithelial neoplasia grade 3 lesions vary by age? An important issue for postvaccination surveillance. Future Microbiol 2012 Feb;7(2):193-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22324989.
  10. 10.010.1 Crowe E, Pandeya N, Brotherton JM, Dobson AJ, Kisely S, Lambert SB, et al. Effectiveness of quadrivalent human papillomavirus vaccine for the prevention of cervical abnormalities: case-control study nested within a population based screening programme in Australia. BMJ 2014 Mar 4;348:g1458 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24594809.
  11. International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical carcinoma and sexual behavior: collaborative reanalysis of individual data on 15,461 women with cervical carcinoma and 29,164 women without cervical carcinoma from 21 epidemiological studies. Cancer Epidemiol Biomarkers Prev 2009 Apr;18(4):1060-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19336546.
  12. Rissel CE, Richters J, Grulich AE, de Visser RO, Smith AM. Sex in Australia: first experiences of vaginal intercourse and oral sex among a representative sample of adults. Aust N Z J Public Health 2003;27(2):131-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14696703.
  13. Rissel C, Heywood W, de Visser RO, Simpson JM, Grulich AE, Badcock PB, et al. First vaginal intercourse and oral sex among a representative sample of Australian adults: the Second Australian Study of Health and Relationships. Sex Health 2014 Nov;11(5):406-15 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25376994.
  14. Moscicki AB, Ma Y, Wibbelsman C, Darragh TM, Powers A, Farhat S, et al. Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescents and young women. Obstet Gynecol 2010 Dec;116(6):1373-80 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21099605.
  15. Monteiro DL, Trajano AJ, Russomano FB, Silva KS. Prognosis of intraepithelial cervical lesion during adolescence in up to two years of follow-up. J Pediatr Adolesc Gynecol 2010 Aug;23(4):230-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20471873.
  16. 16.016.116.2 Wright JD, Davila RM, Pinto KR, Merritt DF, Gibb RK, Rader JS, et al. Cervical dysplasia in adolescents. Obstet Gynecol 2005 Jul;106(1):115-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15994625.
  17. 17.017.1 Moscicki AB, Ma Y, Wibbelsman C, Powers A, Darragh TM, Farhat S, et al. Risks for cervical intraepithelial neoplasia 3 among adolescents and young women with abnormal cytology. Obstet Gynecol 2008 Dec;112(6):1335-42 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19037044.
  18. Sykes P, Harker D, Peddie D. Findings and outcome of teenage women referred for colposcopy at Christchurch Women's Hospital, New Zealand. N Z Med J 2005 Mar 11;118(1211):U1350 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15778751.
  19. Fuchs K, Weitzen S, Wu L, Phipps MG, Boardman LA. Management of cervical intraepithelial neoplasia 2 in adolescent and young women. J Pediatr Adolesc Gynecol 2007 Oct;20(5):269-74 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17868892.
  20. Massad SL, Markwell S, Cejtin HE, Collins Y. Risk of high-grade cervical intraepithelial neoplasia among young women with abnormal screening cytology. J Low Genit Tract Dis 2005 Oct;9(4):225-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16205193.
  21. 21.021.1 Mitchell A; Patrick K; Heywood W; Blackman P; Pitts M. 5th National Survey of Australian Secondary Students and Sexual Health 2013, (ARCSHS Monograph Series No. 97). Melbourne: Australian Research Centre in Sex, Health and Society, La Trobe University; 2014 Available from: http://www.latrobe.edu.au/__data/assets/pdf_file/0004/576661/ARCSHS-SSASH-2013.pdf.
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Appendices

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