Chapter 38 – Screening Policies for Cervical, (Neo-)Vaginal, and Vulvar Dysplasia and Cancer

Summary

As medicine evolves, the traditional healthcare model that reflects societal binary systems is changing to become more inclusive of the transgender population. This is especially true in the field of gynecology and physicians have started to recognize the need for more research in the transgender population as it is particularly vulnerable due to healthcare disparities. Here, we conducted a literature review to help guide for gynecological cancer screening in the transgender population. We found that the transgender population is particularly at risk for infection with the human papilloma virus (HPV) and thus, should be encouraged to undergo preventative vaccination. In this chapter we will highlight screening policies in cervical cancer in the transgender male population, particularly for individuals who have not undergone gender-affirmation surgery. The rarity of vulvar and vaginal cancers in the transgender population have made it difficult to implement routine screening policies and patients should be screened on an individual basis in the presence of concerning symptoms. We also discuss screening skepticism in the transgender population and different techniques physicians can employ to improve their practice. It is our goal that through this chapter a physician can gain a deeper understanding and appreciation when caring for this unique patient population.

38.1 Introduction

Cancers of the lower genital tract, cervical, vaginal, and vulvar cancers, are often preceded by dysplastic changes. The risk factors that predispose to dysplasia include chronic infection with HPV, smoking, obesity, and an immunocompromised state. Currently, there are only screening guidelines available for cervical cancer. Due to the rarity of vaginal and vulvar carcinomas, screening for these cancers is individualized and based on predisposing risk factors.

There is limited data available to the rate of HPV infection and rate of lower genital tract carcinomas in the transgender population and it is difficult to postulate if the same risk factors that predispose the cisgender population equally effect the transgender population in causing dysplastic changes. Transgender patients, however, have decreased access to healthcare, have high rates of smoking, and often cite they do not have sufficient information on evidence-based screening guidelines. In the US, 43% of the cisgender population undergoes screening for lower genital tract cancers whereas only 27% of transmale patients undergo routine Pap smear testing [Reference Dhillon, Oliffe, Kelly and Krist1,Reference McDowell, Pardee and Peitzmeier2]. The purpose of this chapter is to outline the current screening policies for cervical, vulvar, and vaginal cancer as they pertain to the transgender population.

38.2 Cervical Cancer

In 2018, approximately 570,000 cases of cervical cancer and 311,000 deaths from the disease occurred worldwide, with India and China contributing more than one-third of the disease burden [Reference Arbyn, Weiderpass and Bruni3]. Most new cases and deaths affected developing countries [Reference de Martel, Plummer and Vignat4]. The World Health Organization (WHO) has launched a global initiative to prevent and treat cervical cancer in the twenty-first century [Reference Arbyn, Weiderpass and Bruni3,Reference de Martel, Plummer and Vignat4]. The lifetime risk of developing cervical cancer without screening and vaccination in the cisgender population is approximately 2–3.6% in developed nations. Globally, the age-standardized incidence of cervical cancer was 0.013%, with rates in individual countries ranging from less than 2 to 75 per 100,000 people, with the higher incidence rates in developing countries, especially southern Africa [Reference de Martel, Plummer and Vignat4].

Cervical cancer is preceded by HPV infection and dysplastic changes that occur in the cervical transformation zone where the glandular epithelium of the cervical canal meets the squamous epithelium of the ectocervix. Collecting cells from the transformation zone via Pap smear allows screening for dysplastic cells and the presence of HPV. In the US, since the introduction of the Pap smear, the incidence and mortality rate of cervical cancer has decreased by 70% [Reference Safaeian, Solomon and Castle5]. Risk-based management guidelines were developed with the introduction of HPV testing [Reference Safaeian, Solomon and Castle5]. With the combination of screening programs and HPV vaccine, Australia could eliminate cervical cancer by 2028 [Reference Arbyn, Weiderpass and Bruni3,Reference de Martel, Plummer and Vignat4]. Despite primary and secondary prevention, cervical cancer is still a public health concern.

The two most common histological subtypes of cervical cancer are squamous cell carcinoma and adenocarcinoma. Adenocarcinomas have a strong association with obesity and body fat distribution and account for approximately 20–25% of all cervical cancers [Reference Koh, Abu-Rustum and Bean6]. The squamous cell carcinoma histological subtype comprises of 75–80% of all cervical cancers and has been associated with several risk factors such as high-risk sexual activity including multiple sexual partners and lack of barrier contraceptive use, sexually transmitted infections (STIs), immunocompromised states, but mainly persistent HPV infection [Reference Koh, Abu-Rustum and Bean6,Reference Curry, Krist and Owens7]. Infection with HPV can be detected in 99.7% of all cervical cancers [Reference Koh, Abu-Rustum and Bean6] (see also Chapter 36).

Other risk factors that lead to the development of precancerous lesions include smoking, multiparity, long-term oral contraceptive use, and high-risk HPV genotypes, particularly HPV 16 and 18. Nearly 50% of all newly diagnosed cases of cervical cancer cases are in women under the age of 50, with approximately 71% of all cases attributed to HPV16 and HPV18 strains (this percentage rises to nearly 90% when incorporating other high-risk strains of HPV) [Reference Arbyn, Weiderpass and Bruni3]. The incidence of HPV infection in the cisgender population in the US from ages 18–59 was reported to be 39.9% with approximately 20% of infections with high-risk HPV (hr HPV) [Reference Arbyn, Weiderpass and Bruni3]. A similar prevalence of high-risk HPV (16%) in the transgender male population was reported, in self-collected vaginal swabs [Reference Reisner, Deutsch and Peitzmer8]. Globally, the WHO reports a wide range of HPV infections from <3% in Australia and New Zealand to 26% in Sub-Saharan Africa [Reference Arbyn, Weiderpass and Bruni3]. An overwhelmingly large proportion of cervical cancer cases are found in Southeast Asia, Latin America, and Sub-Saharan Africa where there is lack of routine access to primary health care [Reference Arbyn, Weiderpass and Bruni3].

The transgender male population seems to be a vulnerable population for HPV infection and cervical cancer. Some reports suggest that transgender males engage in higher risk sexual activity and have high prevalence of smoking. They also have a unique challenge to access screening when legally recognized as male but still having a uterus and cervix. Many countries have required complete sterilization before legal change of gender, but as these laws are abolished, more transgender males will be able to preserve their uterus and access to screening will be difficult if we don’t adapt [Reference Loughlin9]. The misrepresentation of HPV prevalence in the transgender community is likely attributable to decreased routine screening in the transgender population from lack of healthcare access, negative healthcare experiences, discrimination from medical professionals, and refusal of health services due to body-image dysphoria [Reference McDowell, Pardee and Peitzmeier2,Reference Seay, Ranck and Weiss10].

38.2.1 Screening Guidelines for Cervical Cancer

Screening of cervical cancer is performed via the Pap smear and HPV testing, which sample cells from the ectocervix and endocervix. Current screening guidelines differ worldwide. In the US, the United States Preventative Services Task Force (USPSTF) for trans male and cisgender patient population recommends a Pap smear starting at the age of 21 [Reference Curry, Krist and Owens7,11]. Routine co-testing for hr HPV strains is not recommended before the age of 29 unless dictated by presence of atypical cells of unknown significance [Reference Curry, Krist and Owens7,11]. This is due to the high prevalence and high rate of clearance of HPV in younger patients. For patients from the ages of 29–65 the USPSTF recommends that cervical cytology be obtained every 3 years or hr HPV testing alone every 5 years or have co-testing of cervical cytology and hr HPV testing every 5 years [Reference Curry, Krist and Owens7]. The updated American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines in 2019 note that the same screening guidelines that are used for cisgender patients should be applied to the trans- and gender-diverse population with a uterus in situ [Reference Perkins, Guido and Castle12]. Screening policies also differ substantially from one country to another , regarding the recommended time interval between screening.

Once abnormal cytology is identified, patients often undergo colposcopy and biopsies of the cervix, vagina, or vulva for histologic diagnosis of precancerous lesions [Reference Cooper and Goyal13]. Using 3% acetoacetate, areas of acetowhite lesions, with or without abnormal vasculature (punctation and mosaicism) are identified and biopsied. The management of dysplastic lesions found on biopsies is based on the presence and absence of prior abnormal Pap smears and HPV infections, a key component of the new 2019 ASCCP guidelines [Reference Perkins, Guido and Castle12,Reference Cooper and Goyal13]. After colposcopy, the management of precancerous lesions can be managed conservatively with observation or with surgical procedures such as loop electrode excision procedure (LEEP) or cold knife cone (CKC) biopsy [Reference Koh, Abu-Rustum and Bean6,Reference Perkins, Guido and Castle12].

38.2.2 Special Considerations in the Transgender Population

Though many screening and management guidelines for cervical cancer remain the same for cisgender and transgender patients, there are special considerations that are applicable to the trans male and gender-diverse population. In past literature, it was proposed to start cervical cancer screening with Pap smears prior to transition if this were to happen before the age of 21. Current US guidelines recommend starting screening at 21 years of age regardless of age of transition and age of onset of sexual activity [Reference Patel, Dolitsky and Bachman14]. This is important for patients who initiate testosterone therapy prior to age 21 [Reference Grynberg, Fanchin and Dubost15].

Many patients experience a heightened sense of conflict between gender identity and physical anatomy leading to decreased access to routine health screening. Thus, the decreased reported rate of hr HPV infections might be an underrepresentation of the true incidence of HPV infection. Health care professionals can employ several different techniques to help this unique patient population receive the standard of care. This is done by primarily creating an open dialogue and building a strong physician–patient relationship. During routine gynecological examination it is also important to create a pain-free experience using culturally sensitive language, interviewing prior to disrobing, explaining any physical examination and its necessity, allowing for adequate privacy when patients disrobe, and asking patients to disrobe from waist down only.

Physicians can also utilize patient-collected HPV swabs. When collecting swaps, patients are given privacy in the health examination office and are then asked to swab the inside of the vagina [Reference McDowell, Pardee and Peitzmeier2,Reference Reisner, Deutsch and Peitzmeier16,Reference Wright, Denny, Kuhn, Pollack and Lorincz17]. A study in South Africa showed that patients who utilized a self-collecting swab had a similar sensitivity as a Pap smear when detecting high-grade squamous intraepithelial lesions and invasive carcinoma. However, it is important to note that the limitations of this test lie in its specificity and ability to discern low-grade dysplastic lesions [Reference Wright, Denny, Kuhn, Pollack and Lorincz17].

Also, as mentioned previously, access to cervical cancer screening in patients with legal male gender that still have their uterus might be difficult in some countries.

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